Publications – University of Copenhagen

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Food, Fitness & Pharma > Publications

Publications - UNIK Food, Fitness & Pharma

This list was last updated in June 2015, and only include publications accepted before that date. Hence the list does not include a total overview of all UNIK FFP publications.

Acknowledgements of UNIK in publications

Follow the links below to read the full text and summaries of the scientific papers published by the UNIK ‘Food, Fitness & Pharma' scientists.

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Original papers

Post-Surgical Effects of Roux-En-Y Gastric Bypass on Glucose Homeostasis, Intestinal Morphology and L-Cells in Obese Göttingen Minipigs. Barkholt P, Vegge A, Clausen TR, Birck MM, Fels JJ, Støckel M, Gögenur I, Eriksen T, Holst JJ, Hansen AK, Thymann T, Jelsing J, Sangild PT and Raun K (2015), Avens Publishing Group, J Obes Bariatrics, January 2015 Volume 1, Issue 1
Roux-en-Y gastric bypass (RYGB) is currently the most effective treatment of morbid obesity in man. In rodents, RYGB leads to a number of morphological changes in the intestine. However, little is known about the effect of RYGB surgery on intestinal morphology and enteroendocrine L-cells in larger animals and man. Here we performed RYGB surgery in obese Göttingen minipigs, to assess whether the intervention is associated with changes in intestinal volume, L-cell number and plasma levels of glucose, insulin, glucagon-like peptide-1(GLP-1) and leptin.

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Classical endocannabinoid-like compounds and their regulation by nutrients. Kleberg K, Hassing HA, Hansen HS(2014)BioFactors, 40; 363-372. Endocannabinoid-like compounds are structurally related to the true endocannabinoids but do not contain highly unsaturated fatty acids, and they do not bind the cannabinoid receptors. The classical endocannabinoid-like compounds include N-acylethanolamines and 2-monoacylglycerols, and their structural resemblance to the endocannabinoids makes them players in the endocannabinoid system, where they can interfere with the actions of the true endocannabinoids, because they in several cases engage the same synthesizing and degrading enzymes.

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Role of anorectic N-acylethanolamines in intestinal physiology and satiety control with respect to dietary fat. Hansen HS (2014)Pharmacol Res, 86; 18-25. Anandamide is a well-known agonist for the cannabinoid receptors. Along with endogenous anandamide other non-endocannabinoid N-acylethanolamines are also formed, apparently in higher amounts. These include mainly oleoylethanolamide (OEA), palmitoyelethanolamide (PEA) and linoleoylethanolamide (LEA), and they have biological activity by themselves being anorectic and anti-inflammatory.

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Identification of fatty acids as the dietary component involved in regulation of anorectic intestinal N-acylethanolamines. Diep TA, Madsen AN, Krogh-Hansen S, Al-Sabagh M, Al-Shahwani L, Holst B, Hansen HS (2014) PLoS ONE, 9, e100365

Specificity and sensitivity of commercially available assays for glucagon and oxyntomodulin measurement in human plasma.Bak, M.J.; Wewer Albrechtsen, N.J.; Pedersen, J.; Hartmann, B.; Christensen, M.; Vilsboll, T.; Knop, F.K.; Deacon, C.F.; Dragsted, L.O.; Holst, J.J. Eur J.Endocrinol. 170,4; 529-538(2014a)  AIM: To determine the specificity and sensitivity of assays carried out using commercially available kits for glucagon and/or oxyntomodulin measurements.

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Specificity and sensitivity of commercially available assays for glucagon-like peptide-1 (GLP-1): Implications for GLP-1 measurements in clinical studies. Bak, M.J., Albrechtsen, N.J.W., Pedersen, J., Knop, F., Vilsboll, T., Jørgensen, N.B., Hartmann, B., Deacon, C.F., Dragsted, L.O., Holst,J.J. Diabetes, Obesity and Metabolism (2014) AIMS: To evaluate the performances of commercially available glucagon-like peptide-1 (GLP-1) assays and the implications for clinical studies.

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Extracted oat and barley β-glucans do not affect cholesterol metabolism in young healthy adults. Ibrügger S., Kristensen, M., Poulsen, M.W., Mikkelsen, M.S., Ejsing, J., Jespersen, B.M., Dragsted, L.O., Engelsen, S.B., Bügel, S (2013) J. Nutr. 143 (10) This study investigated the effects of 3 different β-glucan sources, incorporated into a beverage and yogurt, on blood lipids and fecal endpoints. Fourteen participants completed this randomized, crossover, single-blinded study with four 3-wk periods: control and 3.3 g/d oat, barley, and barley mutant β-glucans of similar molecular mass.

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Insulin Detemir treatment in diabetic cats in a practice setting. Hoelmkjaer KM, Spodsberg EM, Bjornvad CR. J Feline Med Surg. 2014 Jun 17. pii: 1098612X14538642. Epub ahead of printing. Insulin detemir is a long-acting insulin analogue and may represent a valuable treatment option for diabetic cats. So far, only one study addressing detemir treatment of diabetic cats has been published, and this was based on an intensive blood glucose monitoring protocol. The aim of the current, retrospective study was to evaluate the effect of detemir therapy in diabetic cats in a general clinical setting.

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Obesity and sex influence insulin resistance and total and multimer adiponectin levels in adult neutered domestic shorthair client-owned cats. Bjornvad CR, Rand JS, Tan HY, Jensen KS, Rose FJ, Armstrong PJ, Whitehead JP. Domest Anim Endocrinol. 2014 Apr;47:55-64. In this study, we estimated insulin sensitivity and determined plasma concentrations of total-, low-molecular-weight (LMW), and high-molecular-weight (HMW) adiponectin and leptin in 72 domestic shorthair, neutered, client-owned cats. Glucose tolerance was assessed with an intravenous glucose tolerance test and body fat percentage (BF%) was measured with dual-energy x-ray absorptiometry.

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Bariatric surgery - effects on obesity and related co-morbidities. Svane M and Madsbad S. Current Diabetes Reviews, 2014. Laparoscopic adjustable gastric banding (LAGB), laparoscopic Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (SG) are the three most commonly performed bariatric procedures. Obesity responds well to bariatric surgery, with major long-lasting weight loss that is most pronounced after RYGB and SG, where the mean weight loss is about 40 kg or 15 body mass index (BMI) units.

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Medicinske komplikationer i forbindelse med bariatrisk kirurgi. Madsbad S. Ugeskrift for læger, Leder 2014; 176: 1449. Den eneste effektive behandling af svær overvægt er bariatrisk kirurgi, der i Danmark hovedsageligt udføres som Roux-en-Y-gastrisk bypasskirurgi, der medfører et vægttab på 40-50 kg. Det store vægttab har sammen med ændringerne i frisætningen af tarmhormoner, der har betydning for appetitreguleringen og insulinsekretionen, en markant effekt på fedmens komorbiditeter, inklusive remission af type 2-diabetes, søvnapnø, metabolisk syndrom, nonalkoholisk fedtlever, belastningssmerter fra knogler og muskler samt hos kvinder en reduktion i risikoen for at få kræftsygdomme.

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Free radical processes in non-enzymatic browning of glucose and lysine. Influence of temperature and unsaturated lipids. Rikke V. Hedegaard, Cecile Santos, Thoo Yin Yin & Leif H. Skibsted. Austr. J. Chem., 67, 2014, 805-812. Formation of dialkylpyrazinium radical cations in aerated 70 % aqueous glycerol solutions of glucose and lysine during heating resulting in browning (90, 110, and 130°C, investigated) was more dependent on temperature than formation of brown colour. Activation energy (Ea) for radical formation was ~83 kJ mol–1, compared with ~70 kJ mol–1 for browning, and was unaffected by methyl linolenate.

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Quantification of radicals formed heating β-lactoglobulin with glucose in aqueous ethanol. Rikke V. Hedegaard, Ling Liu & Leif H. Skibsted. Food Chem., 167, 2014, 185-190. Heating β-lactoglobulin alone, or in the presence of glucose, at moderately elevated temperatures (50, 70 and 80°C) in 30% aqueous ethanol at pH 6.0, 7.0 and 8.0 led to an iron catalysed formation of highly reactive radicals at concentrations of up to 1.0mmol/mol protein as trapped by α-(4-pyridyl N-oxide)-N-tert-butylnitrone (POBN) and quantified by ESR spectroscopy.

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Animal models of infant short bowel syndrome: Translational relevance and challenges. Sangild PT, Ney DM, Sigalet DL, Vegge A, Burrin DG. American Journal of Physiology Gastrointestinal and Liver Physiology (in press 2014)

Acute effects of the glucagon-like peptide 2 analogue, teduglutide, on intestinal adaptation in short bowel syndrome. Thymann T, Stoll B, Mecklenburg L, Burrin DG, Vegge A, Qvist N, Eriksen T, Jeppesen PB, Sangild PT. J Pediatr Gastroenterol Nutr. 2014 Jun. Neonatal short bowel syndrome following massive gut resection is associated with malabsorption of nutrients. The intestinotrophic factor glucagon-like peptide 2 (GLP-2) improves gut function in adult patients with short bowel syndrome, but its effect in pediatric patients remains unknown. Our objective was to test the efficacy of the long-acting synthetic human GLP-2 analogue, teduglutide (ALX-0600), in a neonatal piglet jejunostomy model.

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Invited review: the preterm pig as a model in pediatric gastroenterology. Sangild PT, Thymann T, Schmidt M, Stoll B, Burrin DG, Buddington RK. J Anim Sci. 2013 Oct. This review presents the preterm pig as a translational model in pediatric gastroenterology that has provided new insights into important pediatric diseases such as NEC and SBS. We describe protocols for delivery, care, and handling of preterm pigs, and show how the immature GIT responds to delivery method and different nutritional and therapeutic interventions.

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Effects of PYY3-36 and GLP-1 on energy intake, energy expenditure and appetite in overweight men. Schmidt JB1, Gregersen NT, Pedersen SD, Arentoft JL, Ritz C, Schwartz TW, Holst JJ, Astrup A, Sjödin A. Am J Physiol Endocrinol Metab. 2014 Apr 15. Aim: To examine the effects of GLP-1 and PYY3-36, separately and in combination, on energy intake, energy expenditure, appetite sensations, glucose and fat metabolism, ghrelin and vital signs in healthy overweight men.

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Parenteral lipids and partial enteral nutrition affect hepatic lipid composition but have limited effects on formula-induced necrotizing enterocolitis in preterm piglets. Vegge A, Thymann T, L Lauritzen, SB Bering, B Wiinberg, PT Sangild. 2013b. Clinical Nutrition 2014 Mar 19. Rapid transition from total parenteral nutrition (TPN) to enteral feeding is a risk factor for necrotizing enterocolitis (NEC) in preterm infants. We hypothesized that partial enteral nutrition with colostrum, increased proportion of n-3 polyunsaturated fatty acids (PUFA), or exclusion of lipid in TPN would affect short term NEC sensitivity and liver function.

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Ileal transposition surgery: Gut morphology and endocrine cell numbers in the UCD-T2DM rat. Hansen CF, E Vassiliadis, N Vrang, P Sangild, B Cummings, P Havel and J Jelsing. 2013c. Regulatory Peptides 2014 Feb 7. AIM: To investigate the short-term effect of ileal interposition (IT) surgery on gut morphology and enteroendocrine cell numbers in the pre-diabetic UC Davis type 2 diabetes mellitus (UCD-T2DM) rat.

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Prematurity reduces adaptation to intestinal resection in piglets. Aunsholt L, T Thymann, N Qvist, D Sigalet, S Husby, PT Sangild. 2013b. JPEN J Parenter Enteral Nutr. 2014 Mar 31. Necrotizing enterocolitis and congenital gastrointestinal malformations in infants often require intestinal resection, with a subsequent risk of short bowel syndrome (SBS). We hypothesized that immediate intestinal adaptation following resection of the distal intestine with placement of a jejunostomy differs between preterm and term neonates. 

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Early enhancements of hepatic and later of peripheral insulin sensitivity combined with increased postprandial insulin secretion contribute to improved glycemic control after Roux-en-Y gastric bypass. Bojsen-Møller KN, Dirksen C, Jørgensen NB, Jacobsen SH, Serup AK, Albers PH, Hansen DL, Worm D, Naver LS, Kristiansen VB, Wojtaszewski JFP, Kiens B, Holst JJ, Richter EA, Madsbad S. Diabetes. 2014 May. Roux-en-Y gastric bypass (RYGB) improves glycemic control within days after surgery, and changes in insulin sensitivity and β-cell function are likely to be involved. We studied 10 obese patients with type 2 diabetes (T2D) and 10 obese glucose-tolerant subjects before and 1 week, 3 months, and 1 year after RYGB. Participants were included after a preoperative diet-induced total weight loss of -9.2 ± 1.2%.

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FXR is a molecular target for the effects of vertical sleeve gastrectomy. Ryan KK, Tremaroli V, Clemmensen C, Kovatcheva-Datchary P, Myronovych A, Karns R, Wilson-Perez HE, Sandoval DA, Kohli R, Backhed F, Seeley RJ. Nature 2014. We examined the results of VSG surgery applied to mice with diet-induced obesity and targeted genetic disruption of FXR. Here we demonstrate that the therapeutic value of VSG does not result from mechanical restriction imposed by a smaller stomach. Rather, VSG is associated with increased circulating bile acids, and associated changes to gut microbial communities. Moreover, in the absence of FXR, the ability of VSG to reduce body weight and improve glucose tolerance is substantially reduced...

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Loss of melanocortin-4 receptor function attenuates HPA responses to psychological stress. Ryan KK, Mul JD, Clemmensen C, Egan AE, Begg DP, Halcomb K, Seeley RJ, Herman JP, Ulrich-Lai YM. Psychoneuroendocrinology 2014;42:98-105 The melanocortin 4 receptor (MC4R), well-known for its role in the regulation of energy balance, is widely expressed in stress-regulatory brain regions, including the paraventricular nucleus of the hypothalamus (PVH) and the medial amygdala (MeA). In agreement with this, MC4R has been implicated in hypothalamic-pituitary-adrenocortical axis (HPA) regulation. The present work investigated the role of chronic Mc4r function to modulate basal HPA axis tone and to facilitate acute HPA responses to psychological stress, using a novel rat model with Mc4r loss-of-function...

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Epicatechin and epigallocatechin gallate inhibit formation of intermediary radicals during heating of lysine and glucose. J. Yin, R.V. Hedegaard, L.H. Skibsted, M.L. Andersen. Food Chemistry. Volume 146, 1 March 2014. 
High concentrations of the tea catechins epicatechin (EC) or epigallocatechin gallate (EGCG) inhibited formation of highly reactive intermediary radicals appearing during the Maillard reactions (MR), that take place during heating glucose and lysine at 70 °C in EtOH/HEPES buffer at pH 7.0 and pH 8.0.

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Formation of radicals during heating lysine and glucose in solution with an intermediate water activity. Jie Yin, Mogens L. Andersen, Marianne K. Thomsen, Leif H. Skibsted & Rikke V. Hedegaard. Free Rad. Res., 47, 2013, 643-650. Heating glucose with lysine under alkaline conditions (pH 7.0-10.0) was found to take place with consumption of oxygen together with formation of brown-colored compounds. Highly reactive intermediary radicals were detected when lysine and glucose were heated at intermediate water activity at pH 7.0 and 8.0.

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Effects of gastric bypass surgery on glucose absorption and metabolism during a mixed meal in glucose-tolerant individuals.
Jacobsen SH, Bojsen-Møller KN, Dirksen C, Jørgensen NB, Clausen TR, Wulff BS, Kristiansen VB, Worm D, Hansen DL, Holst JJ, van Hall G, Madsbad S. Diabetologia. 2013 Oct.
Roux-en-Y gastric bypass surgery (RYGB) improves glucose tolerance in patients with type 2 diabetes, but also changes the glucose profile in response to a meal in glucose-tolerant individuals. We hypothesised that the driving force for the changed postprandial glucose profiles after RYGB is rapid entry of glucose into the systemic circulation due to modified gastrointestinal anatomy, causing hypersecretion of insulin and other hormones influencing glucose disappearance and endogenous glucose production...

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GPR41/FFAR3 and GPR43/FFAR2 as cosensors for short-chain fatty acids in enteroendocrine cells vs FFAR3 in enteric neurons and FFAR2 in enteric leukocytes. Nøhr MK, Pedersen MH, Gille A, Egerod KL, Engelstoft MS, Husted AS, Sichlau RM, Grunddal KV, Poulsen SS, Han S, Jones RM, Offermanns S, Schwartz TW. Endocrinology. 2013 Oct.
The expression of short-chain fatty acid receptors GPR41/FFAR3 and GPR43/ free fatty acid receptor 2 (FFAR2) was studied in the gastrointestinal tract of transgenic monomeric red fluorescent protein (mRFP) reporter mice. In the stomach free fatty acid receptor 3 (FFAR3)-mRFP was expressed in a subpopulation of ghrelin and gastrin cells...

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Reduction in cardiovascular risk factors and insulin dose, but no beta-cell regeneration one year after Roux-en-Y gastric bypass in an obese patient with type 1 diabetes: A case report. Carsten Dirksen, Siv H Jacobsen, Kirstine N Bojsen-Møller, Nils B Jørgensen, Lars S Naver, Lisbeth E Hvolris, Dorte Worm, Sten Madsbad, Jens J Holst, Dorte L Hansen. Obesity Research & Clinical Practice 2013; 7: e235-320. Experience with Roux-en-Y gastric bypass in patients with type 1 diabetes is very limited, despite an increasing prevalence of obesity also in this population. We describe changes in anthropometric measures, insulin dose, HbA1c, blood pressure, lipid status, and metabolic response to a liquid mixed meal throughout the first year after RYGB in an obese patient with type 1 diabetes.

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Enteroendocrine cell types revisited. Engelstoft MS, Egerod KL, Lund ML, Schwartz TW. Curr Opin Pharmacol. 2013 Oct.
The GI-tract is profoundly involved in the control of metabolism through peptide hormones secreted from enteroendocrine cells scattered throughout the gut mucosa. A large number of recently generated transgenic reporter mice have allowed for direct characterization of biochemical and cell biological properties of these previously highly elusive enteroendocrine cells...

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Advanced glycation endproducts in food and their effects on health. Poulsen MW, Hedegaard RV, Andersen JM, de Courten B, Bügel S, Nielsen J, Skibsted LH, Dragsted LO. Food Chem Toxicol. 2013 Oct.
Advanced glycation endproducts (AGEs) form by Maillard-reactions after initial binding of aldehydes with amines or amides in heated foods or in living organisms. The mechanisms of formation may include ionic as well as oxidative and radical pathways. The reactions may proceed within proteins to form high-molecular weight (HMW) AGEs or among small molecules to form low-molecular weight (LMW) AGEs...

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Laparoscopic Roux-en-Y gastric bypass in super obese Göttingen minipigs. Birck MM, Vegge A, Støckel M, Gögenur I, Thymann T, Hammelev KP, Sangild PT, Hansen AK, Raun K, von Voss P, Eriksen T. Am J Transl Res. 2013 Sep.
The specific mechanisms behind weight loss and comorbidity improvements in obese patients after Roux-en-Y gastric bypass (RYGBP) are still poorly understood. The aim of this study was to establish and evaluate the feasibility of a long-term survival RYGBP model in super obese Göttingen minipigs in order to improve the translational potential relative to current animal models...

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Oxidative stability and chemical safety of mayonnaise enriched with grape seed extract. Altunkaya A, Hedegaard RV, Harholt J, Brimer L, Gökmen V, Skibsted LH. Food Funct. 2013 Sep.
Grape seed extract (GSE), a by-product from the wine industry, was explored for its use as enrichment to mayonnaise, due to its potential health effects. Mayonnaises were enriched with 0 mg GSE per mL, 0.5 mg GSE per mL (∼0.050%), 0.9 mg GSE per mL (∼0.10%) and 1.4 mg GSE per mL (∼0.15%) during preparation and stored in the dark at room temperature for 8 weeks...

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Exaggerated Glucagon-Like Peptide 1 Response Is Important for Improved β-Cell Function and Glucose Tolerance After Roux-en-Y Gastric Bypass in Patients With Type 2 Diabetes. Jørgensen NB, Dirksen C, Bojsen-Møller KN, Jacobsen SH, Worm D, Hansen DL, Kristiansen VB, Naver L, Madsbad S, Holst JJ. Diabetes. 2013 Sep.
β-Cell function improves in patients with type 2 diabetes in response to an oral glucose stimulus after Roux-en-Y gastric bypass (RYGB) surgery. This has been linked to the exaggerated secretion of glucagon-like peptide 1 (GLP-1), but causality has not been established. The aim of this study was to investigate the role of GLP-1 in improving β-cell function and glucose tolerance and regulating glucagon release after RYGB using exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R)-specific antagonist...

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Delineation of the GPRC6A receptor signaling pathways using a mammalian cell line stably expressing the receptor. Jacobsen SE, Norskov-Lauritsen L, Thomsen AR, Smajilovic S, Wellendorph P, Larsson NH, Lehmann A, Bhatia VK, Brauner-Osborne H. J Pharmacol Exp Ther. 2013 Sep.
The GPRC6A receptor is a recently deorphanized class C G protein-coupled receptor. We and others have shown that the receptor is co-activated by basic L-α-amino acids and divalent cations whereas other groups have also suggested osteocalcin and testosterone to be agonists. Likewise, the GPRC6A receptor has been suggested to couple to multiple G protein classes albeit via indirect methods...

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Oral L-arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice. Clemmensen C, Smajilovic S, Smith EP, Woods SC, Bräuner-Osborne H, Seeley RJ, D'Alessio DA, Ryan KK. Endocrinology. 2013 Aug.
Pharmacologic and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet-induced obesity, may provide an alternative therapeutic approach...

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The G protein-coupled receptor, class C, group 6, subtype A (GPRC6A) receptor: From cloning to physiological function. Clemmensen C, Smajilovic S, Wellendorph P, Bräuner-Osborne H. Br J Pharmacol. 2013 Aug.
GPRC6A (G protein-coupled receptor, class C, group 6, subtype A) is a class C G protein-coupled receptor, that has been cloned from human, mouse and rat. Several groups have shown that the receptor is activated by a range of basic and small aliphatic L-α-amino acids of which L-arginine, L-lysine and L-ornithine are the most potent compounds with EC50 values in the mid micromolar range...

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Effect of dietary advanced glycation end products on postprandial appetite, inflammation, and endothelial activation in healthy overweight individuals. Poulsen MW, Bak MJ, Andersen JM, Monošík R, Giraudi-Futin AC, Holst JJ, Nielsen J, Lauritzen L, Larsen LH, Bügel S, Dragsted LO. Eur J Nutr. 2013 Aug.
Advanced glycation end products (AGEs) formed in food during high-heat cooking may induce overeating and inflammation. We investigated whether AGE contents in a single meal affect postprandial appetite and markers of inflammation, endothelial activation, and oxidative stress...

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Consumption of a Diet Low in Advanced Glycation Endproducts for 4 weeks Improves Insulin Sensitivity in Overweight Women. Mark AB, Poulsen MW, Andersen S, Andersen JM, Bak MJ, Ritz C, Holst JJ, Nielsen J, de Courten B, Dragsted LO, Bügel S. Diabetes Care. 2013 Aug.
ObjectiveHigh heat cooking of food induces formation of advanced glycation endproducts (AGEs), which are thought to impair glucose metabolism in type 2 diabetic patients. High intake of fructose might additionally affect endogenous formation of AGEs...

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Promiscuous Seven Transmembrane Receptors Sensing L-a-amino Acids. Smajilovic S, Wellendorph P, Bräuner-Osborne H. Curr Pharm Des. 2013 Jul.
A number of nutrient sensing seven trans-membrane (7TM) receptors have been identified and characterized over the past few years. While the sensing mechanisms to carbohydrates and free fatty acids are well understood, the molecular basis of amino acid sensing has recently come to the limelight...

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Increased hepatic insulin clearance after Roux-en-Y gastric bypass. Bojsen-Møller KN, Dirksen C, Jørgensen NB, Jacobsen SH, Hansen DL, Worm D, Naver L, Kristiansen VB, Holst JJ, Madsbad S. J Clin Endocrinol Metab. 2013 Jun.
The objective of the investigation was to study changes in insulin clearance after RYGB...

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Enhanced voluntary wheel running in GPRC6A receptor knockout mice. Clemmensen C, Pehmøller C, Klein AB, Ratner C, Wojtaszewski JF, Bräuner-Osborne H. Physiol Behav. 2013 Jun 13. GPRC6A is an amino acid-sensing receptor highly expressed in the brain and in skeletal muscle. Although recent evidence suggests that genetically engineered GPRC6A receptor knockout (KO) mice are susceptible to develop subtle endocrine and metabolic disturbances, the underlying disruptions in energy metabolism are largely unexplored. Based on GPRC6A's expression pattern and ligand preferences, we hypothesize that the receptor may impact energy metabolism via regulating physical activity levels.

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N-acylation of phosphatidylethanolamine and its biological functions in mammals. Wellner N, Diep TA, Janfelt C, Hansen HS. Biochim Biophys Acta. 2013 Mar. This paper reviews the metabolism, occurrence and assay of NAPE and pNAPE, and discusses the putative biological functions in mammals of these phospholipids. This article is part of a Special Issue entitled Phospholipids and Phospholipid Metabolism.

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Effect of diet on tissue levels of palmitoylethanolamide. Hansen HS, CNS Neurol Disord Drug Targets. 2013 Feb. Palmitoylethanolamide (PEA) as well as the other N-acylethanolamines (NAEs), e.g. anandamide, oleoylethanolamide, stearoylethanolamide and linoleoylethanolamide, appear to exist in every mammalian cell at low levels, e.g. a few hundred pmol/g tissue for PEA. Their formation can be stimulated by cellular injury and inflammation. In the brain PEA and other NAEs may have neuroprotective functions.

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Advanced glycation endproducts in food and their effects on health. Poulsen MW, Hedegaard RV, Andersen JM, de Courten B, Bügel S, Nielsen J, Skibsted LH, Dragsted LO. Food Chem Toxicol. 2013 Jul 16;60C:10-37. doi: 10.1016/j.fct.2013.06.052. [Epub ahead of print]. Advanced glycation endproducts (AGEs) form by Maillard-reactions after initial binding of aldehydes with amines or amides in heated foods or in living organisms. The mechanisms of formation may include ionic as well as oxidative and radical pathways. The reactions may proceed within proteins to form high-molecular weight (HMW) AGEs or among small molecules to form low-molecular weight (LMW) AGEs. All free amino acids form AGEs, but lysine or arginine side chains dominate AGE formation within proteins...

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Formation of radicals during heating lysine and glucose in solution with an intermediate water activity. Yin J, Andersen ML, Thomsen MK, Skibsted LH, Hedegaard RV. Free Radic Res. 2013 Aug;47(8):643-50. doi: 10.3109/10715762.2013.812206. Epub 2013 Jun 28.Abstract Heating glucose with lysine under alkaline conditions (pH 7.0-10.0) was found to take place with consumption of oxygen together with formation of brown-colored compounds. Highly reactive intermediary radicals were detected when lysine and glucose were heated at intermediate water activity at pH 7.0 and 8.0. The detection was based on initial trapping of highly reactive radicals by ethanol followed by spin trapping of 1-hydroxyethylradicals with α-(4-pyridyl N-oxide)-N-tert-butylnitrone (POBN) and Electron Spin Resonance (ESR) spectroscopy...

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Antioxidant capacity versus chemical safety of wheat bread enriched with pomegranate peel powder. Altunkaya A, Hedegaard RV, Brimer L, Gökmen V, Skibsted LH. Food Funct. 2013 Apr  
Pomegranate peel powder (PP), a by-product of the pomegranate juice industry rich in polyphenols, was explored for use in bread production, due to its potential health effects. Wheat bread was prepared using different levels for replacement of flour with PP (0 to 10 g per 100 g flour) resulting in antioxidant levels expressed as Trolox equivalent antioxidant capacity values (TEAC) ranging from 1.8 to 6.8 μmol TEAC per g bread for fresh bread. TEAC remained constant during 5 days of storage in polyethylene bags at room temperature...

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Formation of Advanced Glycation End Products (AGEs) are Influenced by Lipids in Milk Powders Ling Liu, Rikke V. Hedegaard and Leif H. Skibsted Australian Journal of Chemistry. Advanced glycation end products (AGEs) were determined by a polyclonal ELISA method in three milk powders of varying lipid content, during storage in sealed containers at 65°C for up to 20 days. AGEs content correlated with increased water activity (aw), decreased glass transition temperature (Tg), increased lactose crystallisation, and browning in the three milk powders.

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Palatability and chemical safety of apple juice fortified with pomegranate peel extract. Dinçay A, Hedegaard R, Harholt J, Brimer L, Gökmen V and  Skibsted LH. Food Function, 2013, Accepted Manuscript DOI: 10.1039/C3FO60150A. Pomegranate peel extract (PPE), a by-product of pomegranate juice industry with potential health effects, was explored for use as fortification of reconstituted apple juice in the concentration range 0.5 to 2.0% (w/w). Radical scavenging capacity and antioxidative of the fortified apple juices was estimated using, (i) electron spin resonance (ESR) to quantify their ability to scavenge the stable radical Fremy’s salt, and (ii) the Trolox equivalent antioxidant capacity assay (TEAC) and compared to apple juice without fortification as control...

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Shelf-life of food powders R. V. Hedegaard and L. H. Skibsted Chapter 16 in “Handbook of food powders: Processes and properties” Edited by B Bhandari, N Bansal, University of Queensland, Australia, M Zhang, Jiangnan University, China and P Schuck, INRA, France.

Glucagon-Like Peptide-2 Induces Rapid Digestive Adaptation Following Intestinal Resection in Preterm Neonates. Vegge A, Thymann T, Lund P, Stoll B, Bering SB, Hartmann B, Jelsing J, Qvist N, Burrin DG, Jeppesen PB, Holst JJ, Sangild PT. Am J Physiol Gastrointest Liver Physiol, Jun 2013

Short bowel syndrome (SBS) is a frequent complication after intestinal resection in infants suffering from intestinal disease. We tested whether treatment with the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) increases intestinal volume and function in the period immediately following intestinal resection in preterm pigs. Preterm pigs were fed enterally for 48 hours before undergoing resection of 50% of the small intestine and establishment of a jejunostomy.

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Hypertrophy Dependent Doubling of L-Cells in Roux-en-Y Gastric Bypass Operated Rats. Hansen CF, Bueter M, Theis N, Lutz T, Paulsen S, Dalbøge LS, Vrang N, Jelsing J. PLoS One, Jun 2013

Roux-en-Y gastric bypass (RYGB) leads to a rapid remission of type 2 diabetes mellitus (T2DM), but the underlying mode of action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are thought to play a central role in the anti-diabetic effects of RYGB; therefore, an improved understanding of intestinal endocrine L-cell adaptability is considered pivotal.

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Novel insight into the distribution of L-cells in the rat intestinal tract. Hansen CF, Vrang N, Sangild PT, Jelsing J. Am J Transl Res, Apr 2013

Gut secreted incretin hormones and gastric bypass surgery currently provides some of the most successful treatments for diabetes and obesity respectively. However, despite the evident importance of the gut endocrine system no information exists on the total number and distribution of different types of endocrine cells in the gut. Here we have used the established preclinical Zucker Diabetic Fatty (ZDF) rat model...

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2-Heptyl-Formononetin Increases Cholesterol and Induces Hepatic Steatosis in Mice. Charlotte Andersen, Janne G. Schjoldager, Christian G. Tortzen, Andreas Vegge, Majbritt R. Hufeldt, Mette T. Skaanild, Finn K. Vogensen, Karsten Kristiansen, Axel K. Hansen, and John Nielsen. BioMed Research International. Mar 2013
Consumption of isoflavones may prevent adiposity, hepatic steatosis, and dyslipidaemia. However, studies in the area are few and primarily with genistein. This study investigated the effects of formononetin and its synthetic analogue, 2-heptyl-formononetin (C7F), on lipid and cholesterol metabolism in C57BL/6J mice. 

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Increased susceptibility to diet-induced obesity in GPRC6A receptor knockout mice. Clemmensen C, Smajilovic S, Madsen AN, Klein AB, Holst B, Bräuner-Osborne H. J Endocrinol. Feb 2013
The recently identified G protein-coupled receptor GPRC6A is activated by dietary amino acids and expressed in multiple tissues. Although the receptor is hypothesized to exert biological impact on metabolic and endocrine-related parameters the role of the receptor in obesity and metabolic complications is still elusive. In the present study, we investigated the impact of GPRC6A deficiency in a murine model of diet-induced obesity. Male GPRC6A knockout (KO) mice and wild-type (WT) littermates were subjected to a high-fat diet (HFD) for 25 weeks and exposed to...

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Gut hormones, early dumping and resting energy expenditure in patients with good and poor weight loss response after Roux-en-Y gastric bypass. Dirksen C, Jørgensen NB, Bojsen-Møller KN, Kielgast U, Jacobsen SH, Clausen TR, Worm D, Hartmann B, Rehfeld JF, Damgaard M, Madsen JL, Madsbad S, Holst JJ, Hansen DL. Int J Obes (Lond). Feb 2013
Objective:To identify factors contributing to the variation in weight loss after Roux-en-Y gastric bypass (RYGB).Design:Cross-sectional study of patients with good (excess body mass index lost (EBL) >60%) and poor weight loss response (EBL <50%) >12 months after RYGB and a lean control group matched for age and gender.Materials and methods:Sixteen patients with good weight loss...

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Fast pouch emptying, delayed small intestinal transit, and exaggerated gut hormone responses after Roux-en-Y gastric bypass. Dirksen C, Damgaard M, Bojsen-Møller KN, Jørgensen NB, Kielgast U, Jacobsen SH, Naver LS, Worm D, Holst JJ, Madsbad S, Hansen DL, Madsen JL. Neurogastroenterol Motil. Jan 2013
BACKGROUND:Roux-en-Y gastric bypass (RYGB) causes extensive changes in gastrointestinal anatomy and leads to reduced appetite and large weight loss, which partly is due to an exaggerated release of anorexigenic gut hormones. METHODS: To examine whether the altered passage of foods through the gastrointestinal tract after RYGB could be responsible for the changes in gut hormone release, we studied gastrointestinal motility with a scintigraphic technique as well as...

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Molecular structure of large-scale extracted β-glucan from barley and oat: Identification of a significantly changed block structure in a high β-glucan barley mutant. Mikkelsen MS, Jespersen BM, Larsen FH, Blennow A, Engelsen SB. Food Chem. 2013
Health effects of β-glucan are typically related to dose, size and viscosity without taking the specific molecular structure into account. High β-glucan mutant barley, mother barley and oat β-glucans were large-scale extracted by comparable protocols using hot water, enzyme assisted hydrolysis and ethanol precipitation leading to similar molecular masses (200-300kDa)....

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Bovine Colostrum to Children With Short Bowel Syndrome: A Randomized, Double-Blind, Crossover Pilot Study. Aunsholt L, Jeppesen PB, Lund P, Sangild PT, Ifaoui IB, Qvist N, Husby S. JPEN J Parenter Enteral Nutr. Dec 2012: Aim: The efficacy of bovine colostrum to improve intestinal function in children with SBS was evaluated by metabolic balance studies. Materials and Methods: Nine children with SBS were included in a randomized, double-blind, crossover study. Twenty percent of enteral fluid intake was replaced with bovine colostrum or a mixed milk diet for 4 weeks, separated by a 4-week washout period. Intestinal absorption of energy and wet weight was used to assess intestinal function and the efficacy of colostrum...

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Understanding adiponectin in dogs and cats: a work in progress. Verkest KR, Bjornvad CR. Vet J. 2012 Jul;193(1):4-5.  

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Extracellular Ca2+ is a danger signal activating the NLRP3 inflammasome through G protein-coupled calcium sensing receptors. Manuela Rossol, Matthias Pierer, Nora Raulien, Dagmar Quandt, Undine Meusch, Kathrin Rothe, Kristin Schubert, Torsten Schöneberg, Michael Schaefer, Ute Krügel, Sanela Smajilovic, Hans Braüner-Osborne, Christoph Baerwald & Ulf Wagner. Nat Commun. Dec 2012
Activation of the NLRP3 inflammasome enables monocytes and macrophages to release high levels of interleukin-1β during inflammatory responses. Concentrations of extracellular calcium can increase at sites of infection, inflammation or cell activation. Here we show that increased extracellular calcium activates the NLRP3 inflammasome via stimulation of G protein-coupled calcium sensing receptors. Activation is mediated by signalling...

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A major lineage of enteroendocrine cells coexpress CCK, secretin, GIP, GLP-1, PYY, and neurotensin but not somatostatin. Egerod KL, Engelstoft MS, Grunddal KV, Nøhr MK, Secher A, Sakata I, Pedersen J, Windeløv JA, Füchtbauer EM, Olsen J, Sundler F, Christensen JP, Wierup N, Olsen JV, Holst JJ, Zigman JM, Poulsen SS, Schwartz TW. Endocrinology. Dec 2012

Enteroendocrine cells such as duodenal cholecystokinin (CCK cells) are generally thought to be confined to certain segments of the gastrointestinal (GI) tract and to store and release peptides derived from only a single peptide precursor. In the current study, however, transgenic mice expressing enhanced green fluorescent protein (eGFP) under...

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Antioxidant synergism between ethanolic Centella asiatica extracts and α-tocopherol in model systems. Thoo YY, Abas F, Lai OM, Ho CW, Yin J, Hedegaard RV, Skibsted LH, Tan CP. Food Chem, Epub Nov 2012.
The synergistic antioxidant effects of ethanolic extracts of Centella asiatica (CE), and α-tocopherol have been studied. The types of interactions exhibited by CE and α-tocopherol combined at different ratios were measured using three assays: 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulphonic acid) diammonium salt (ABTS) radical-scavenging capacity, the β-carotene bleaching system and liposome peroxidation assays. Fixed-fraction isobolographic analysis was used to detect...

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Acylation Type Determines Ghrelin's Effects on Energy Homeostasis in Rodents Endocrinology. Heppner KM, Chaudhary N, Müller TD, Kirchner H, Habegger KM, Ottaway N, Smiley DL, Dimarchi R, Hof-mann SM, Woods SC, Sivertsen B, Holst B, Pfluger PT, Perez-Tilve D, Tschöp MH. 2012 Oct
Ghrelin is a gastrointestinal polypeptide that acts through the ghrelin receptor (GHSR) to promote food intake and increase adiposity. Activation of GHSR requires the presence of a fatty-acid (FA) side chain on amino acid residue serine 3 of the ghrelin molecule. However, little is known about the role that the type of FA used for acylation plays in the biological action of ghrelin.

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Divalent metal transporter 1 regulates iron-mediated ROS and pancreatic β cell fate in response to cytokines. Hansen JB, Tonnesen MF, Madsen AN, Hagedorn PH, Friberg J, Grunnet LG, Heller RS, Nielsen AØ, Størling J, Baeyens L, Anker-Kitai L, Qvortrup K, Bouwens L, Efrat S, Aalund M, Andrews NC, Billestrup N, Karlsen AE, Holst B, Pociot F, Mandrup-Poulsen T. Cell Metab. Oct 2012
Cell MetabolismReactive oxygen species (ROS) contribute to target-cell damage in inflammatory and iron-overload diseases. Little is known about iron transport regulation during inflammatory attack. Through a combination of in vitro and in vivo studies, we show that the proinflammatory cytokine IL-1β induces divalent metal transporter 1 (DMT1) expression correlating with increased β cell iron content and ROS production. Iron chelation and siRNA and genetic knockdown of DMT1 expression...

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An Aromatic Region To Induce a Switch between Agonism and Inverse Agonism at the Ghrelin Receptor. Els S, Schild E, Petersen PS, Kilian TM, Mokrosinski J, Frimurer TM, Chollet C, Schwartz TW, Holst B, Beck-Sickinger AG. J Med Chem. 2012 Sep
The ghrelin receptor displays a high constitutive activity suggested to be involved in the regulation of appetite and food intake. Here, we have created peptides with small changes in the core binding motif -wFw- of the hexapeptide KwFwLL-NH(2) that can swap the peptide behavior from inverse agonism to agonism, indicating the importance of this sequence.

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L-Arginine improves multiple physiological parameters in mice exposed to diet-induced metabolic disturbances. Clemmensen C, Madsen AN, Smajilovic S, Holst B, Bräuner-Osborne H. Amino Acids. 2012 Sep
L-Arginine (L-Arg) is a conditionally essential amino acid and a natural constituent of dietary proteins. Studies in obese rats and type 2 diabetic humans have indicated that dietary supplementation with L-Arg can diminish gain in white adipose tissue (WAT) and improve insulin sensitivity. However, the effects of L-Arg on glucose homeostasis, body composition and energy metabolism remain unclear....

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Modulation of constitutive activity and signaling bias of the ghrelin receptor by conformational constraint in the second extracellular loop. Mokrosinski J, Frimurer TM, Sivertsen B, Schwartz TW, Holst B. J Biol Chem. 2012 Sep
Based on a rare, natural Glu for Ala-204(C+6) variant located six residues after the conserved Cys residue in extracellular loop 2b (ECL2b) associated with selective elimination of the high constitutive signaling of the ghrelin receptor, this loop was subjected to a detailed structure functional analysis. Introduction of Glu in different positions demonstrated that although the constitutive signaling was partly reduced when introduced in position 205(C+7) it was only totally eliminated in position 204(C+6)....

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Early life treatment with vancomycin propagates Akkermansia muciniphila and reduces diabetes incidence in the NOD mouse. Hansen CH, Krych L, Nielsen DS, Vogensen FK, Hansen LH, Sørensen SJ, Buschard K, Hansen AK.Diabetologia. 2012 Aug
Increasing evidence suggests that environmental factors changing the normal colonisation pattern in the gut strongly influence the risk of developing autoimmune diabetes. The aim of this study was to investigate, both during infancy and adulthood, whether treatment with vancomycin, a glycopeptide antibiotic specifically directed against Gram-positive bacteria, could influence immune homeostasis and the development of diabetic symptoms in the NOD mouse model for diabetes....

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GPR119 as a fat sensor. Hansen HS, Rosenkilde MM, Holst JJ, Schwartz TW. Trends Pharmacol Sci. 2012 Jul.
The GPR119 receptor is expressed predominantly in pancreatic β cells and in enteroendocrine cells. It is a major target for the development of anti-diabetic drugs that through GPR119 activation may stimulate both insulin and GLP-1 release...

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Changes in gastrointestinal hormone responses, insulin sensitivity, and beta-cell function within 2 weeks after gastric bypass in non-diabetic subjects. Jacobsen SH, Olesen SC, Dirksen C, Jørgensen NB, Bojsen-Møller KN, Kielgast U, Worm D, Almdal T, Naver LS, Hvolris LE, Rehfeld JF, Wulff BS, Clausen TR, Hansen DL, Holst JJ, Madsbad S. Obes Surg. 2012 Jul
Roux-en-Y gastric bypass (RYGB) surgery causes profound changes in secretion of gastrointestinal hormones and glucose metabolism. We present a detailed analysis of the early hormone changes after RYGB in response to three different oral test meals designed to provide this information without causing side effects (such as dumping)....

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The L: -α-amino acid receptor GPRC6A is expressed in the islets of Langerhans but is not involved in L: -arginine-induced insulin release. Smajilovic S, Clemmensen C, Johansen LD, Wellendorph P, Holst JJ, Thams PG, Ogo E, Bräuner-Osborne H. Amino Acids. 2012 Jun
GPRC6A is a seven-transmembrane receptor activated by a wide range of L: -α-amino acids, most potently by L: -arginine and other basic amino acids. The receptor is broadly expressed, but its exact physiological role remains to be elucidated. It is well established that L: -arginine stimulates insulin secretion; therefore, the receptor has been hypothesized to have a role in regulating glucose metabolism....

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GPR119 as a fat sensor. Hansen HS, Rosenkilde MM, Holst JJ, Schwartz TW. Trends Pharmacol Sci. 2012 May 2.
The GPR119 receptor is expressed predominantly in pancreatic β cells and in enteroendocrine cells. It is a major target for the development of anti-diabetic drugs that through GPR119 activation may stimulate both insulin and GLP-1 release. GPR119 can be activated by oleoylethanolamide and several other endogenous lipids containing oleic acid: these include N-oleoyl-dopamine, 1-oleoyl-lysophosphatidylcholine, generated in the tissue, and 2-oleoyl glycerol generated in the gut lumen. Thus, the well-known stimulation of GLP-1 release by dietary fat is probably not only mediated by free fatty acids acting through, for example, GPR40, but is also probably mediated in large part through the luminal formation of 2-monoacylglycerol acting on the 'fat sensor' GPR119....

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Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass. Dirksen C, Jørgensen NB, Bojsen-Møller KN, Jacobsen SH, Hansen DL, Worm D, Holst JJ, Madsbad S. Diabetologia. 2012 Apr 27.
Roux-en-Y gastric bypass (RYGB) greatly improves glycaemic control in morbidly obese patients with type 2 diabetes, in many even before significant weight loss. Understanding the responsible mechanisms may contribute to our knowledge of the pathophysiology of type 2 diabetes and help identify new drug targets or improve surgical techniques. This review summarises the present knowledge based on pathophysiological studies published during the last decade....

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Acute and long-term effects of Roux-en-Y gastric bypass on glucose metabolism in subjects with type 2 diabetes and normal glucose tolerance. Jorgensen NB, Jacobsen SH, Dirksen C, Bojsen-Moller KN, Naver L, Hvolris L, Clausen TR, Wulff BS, Worm D, Hansen DL, Madsbad S, Holst JJ. Am J Physiol Endocrinol Metab. 2012 Apr 24. 
Aims: To study the potential mechanisms responsible for the improvement in glucose control in type 2 diabetes (T2D) within days after Roux-en-Y gastric bypass (RYGB). Method: Thirteen obese subjects with T2D and twelve matched subjects with normal glucose tolerance (NGT) were examined during a liquid meal before (pre), one week (1 wk), 3 months and 1 year after RYGB. Glucose, insulin, C-peptide, GLP-1, GIP and glucagon concentrations were measured. Insulin resistance (HOMA-IR), beta cell glucose sensitivity (β-GS) and disposition index (D(β-GS): β-GS x 1/HOMA-IR) were calculated....

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Patterns of early gut colonization shape future immune responses of the host. Hansen CH, Nielsen DS, Kverka M, Zakostelska Z, Klimesova K, Hudcovic T, Tlaskalova-Hogenova H, Hansen AK. PLoS One. 2012;7(3):e34043. Epub 2012 Mar 27. 
The most important trigger for immune system development is the exposure to microbial components immediately after birth. Moreover, targeted manipulation of the microbiota can be used to change host susceptibility to immune-mediated diseases. Our aim was to analyze how differences in early gut colonization patterns change the composition of the resident microbiota and future immune system reactivity....

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L-Arginine improves multiple physiolog-ical parameters in mice exposed to diet-induced metabolic disturbances. Clemmensen C, Madsen AN, Smajilovic S, Holst B, Bräuner-Osborne H. Amino Acids. 2011 Dec
L-Arginine (L-Arg) is a conditionally essential amino acid and a natural constituent of dietary proteins. Studies in obese rats and type 2 diabetic humans have indicated that dietary supplementation with L-Arg can diminish gain in white adipose tissue (WAT) and improve insulin sensitivity. However, the effects of L-Arg on glucose homeostasis, body composition and energy metabolism remain unclear.

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Chemogenomic discovery of allosteric antagonists at the GPRC6A receptor. Gloriam DE, Wellendorph P, Johansen LD, Thomsen AR, Phonekeo K, Pedersen DS, Bräuner-Osborne H. Chem Biol. 2011 Nov
GPRC6A is a Family C G protein-coupled receptor recently discovered and deorphanized by our group. This study integrates chemogenomic ligand inference, homology modeling, compound synthesis, and pharmacological mechanism-of-action studies to disclose two noticeable results of methodological and pharmacological character.... 

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Deficiency of the GPR39 receptor is associated with obesity and altered adipocyte metabolism. Petersen PS, Jin C, Madsen AN, Rasmussen M, Kuhre R, Egerod KL, Nielsen LB, Schwartz TW, Holst B. FASEB J. 2011 Nov
GPR39, a constitutively active 7TM receptor important for glucose-induced insulin secretion and maturation of pancreatic β-cell function, is up-regulated in adipose tissue on abstinence from food and chemically induced diabetes. In the present study, we investigated the effect of GPR39 deficiency on body weight and adipocyte metabolism....

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Gastric bypass and duodenal and gastric feeding: a comment to Hansen et al. Jorgensen NB, Dirksen C, Holst JJ, Madsbad S. 2011 Nov
Comment on Role of the foregut in the early improvement in glucose tolerance and insulin sensitivity following Roux-en-Y gastric bypass surgery.

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Convenient Synthesis of Nε-(Carboxymethyl)lysine, a Key Advanced Glycation Endproduct Biomarker. Jeanette M. Andersen, Thomas Hjelmgaard, Lars O. Dragsted, John Nielsen. October 2011
Advanced glycation endproducts (AGEs) are formed when sugars react with peptides and proteins without the help of enzymes and by thermal processing of food such as baking and frying. AGEs and especially Nε-(carboxymethyl)lysine (CML) has been used as general key biomarkers for oxidative stress and a number of diseases associated with poor lifestyle. Herein we present the first synthetic pathway to the free zwitter ion of CML via a protected intermediate.... 

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Studies on the anorectic effect of N-acylphosphatidylethanolamine and phosphatidylethanolamine in mice. Wellner N, Tsuboi K, Madsen AN, Holst B, Diep TA, Nakao M, Tokumura A, Burns MP, Deutsch DG, Ueda N, Hansen HS. Biochim Biophys Acta. 2011 Sep
N-acyl-phosphatidylethanolamine is a precursor phospholipid for anandamide, oleoylethanolamide, and other N-acylethanolamines, and it may in itself have biological functions in cell membranes. Recently, N-palmitoyl-phosphatidylethanolamine (NAPE) has been reported to function as an anorectic hormone secreted from the gut and acting on the brain (Gillum et al., [5]). In the current study, two of our laboratories independently investigated whether NAPE metabolites may be involved in mediating the anorectic action of NAPE i.p. injected in mice....

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2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans.
Hansen KB, Rosenkilde MM, Knop FK, Wellner N, Diep TA, Rehfeld JF, Andersen UB, Holst JJ, Hansen HS. J Clin Endocrinol Metab. 2011 Sep
Dietary fat is thought to stimulate release of incretin hormones via activation of fatty acid receptors in the intestine. However, dietary fat (triacylglycerol) is digested to 2-monoacylglycerol and fatty acids. Activation of G protein-coupled receptor 119 (GPR119) stimulates glucagon-like peptide-1 (GLP-1) release from the intestinal L-cells. We aimed to investigate if 2-oleoyl glycerol (2OG) can activate GPR119 in vitro and stimulate GLP-1 secretion in vivo....

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Safety, tolerability and sustained weight loss over 2 years with the once-daily human GLP-1 analog, liraglutide. Astrup A, Carraro R, Finer N, Harper A, Kunesova M, Lean ME, Niskanen L, Rasmussen MF, Rissanen A, Rössner S, Savolainen MJ, Van Gaal L. 2011 Aug 16
The paper evaluates safety, tolerability and long-term efficacy of the GLP_1 analog, liraglutide, for sustaining weight loss over 2 years. The study is based in more than 500 adults from 19 European clinical research centers, and concludes that Liraglutide is well tolerated, sustains weight loss over 2 years and improves cardiovascular risk factors....

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Unique interaction pattern for a functionally biased ghrelin receptor agonist. Sivertsen B, Lang M, Frimurer TM, Holliday ND, Bach A, Els S, Engelstoft MS, Petersen PS, Madsen AN, Schwartz TW, Beck-Sickinger AG, Holst B.  J Biol Chem. 2011 Jun 10;286(23):20845-60.
Based on the conformationally constrained D-Trp-Phe-D-Trp (wFw) core of the prototype inverse agonist [D-Arg(1),D-Phe(5),D-Trp(7,9),Leu(11)]substance P, a series of novel, small, peptide-mimetic agonists for the ghrelin receptor were generated. By using various simple, ring-constrained spacers connecting the D-Trp-Phe-D-Trp motif with the important C-terminal carboxyamide group, 40 nm agonism potency was obtained and also in one case (wFw-Isn-NH(2), where Isn is isonipecotic acid) ~80% efficacy. However, in contrast to all previously reported ghrelin receptor agonists, the piperidine-constrained wFw-Isn-NH(2) was found to be a functionally biased agonist....

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Manipulation of the gut microbiota in C57BL/6 mice changes glucose tolerance without affecting weight development and gut mucosal immunity. Bech-Nielsen GV, Hansen CH, Hufeldt MR, Nielsen DS, Aasted B, Vogensen FK, Midtvedt T, Hansen AK. Res Vet Sci. 2011 May
Inflammatory diseases such as type 2 diabetes (T2D) in humans and mice are under the influence of the composition of the gut microbiota (GM). It was previously demonstrated that treating Lep(ob) mice with antibiotics improved glucose tolerance. However, wild type C57BL/6J mice may also exhibit plasma glucose intolerance reminiscent of human T2D. We hypothesized that antibiotic treatment in C57BL/6 mice would have an impact on glucose tolerance without affecting weight and gut immunology....

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Manipulation of the gut microbiota in C57BL/6 mice changes glucose tolerance without affecting weight development and gut mucosal immunity. Bech-Nielsen GV, Hansen CH, Hufeldt MR, Nielsen DS, Aasted B, Vogensen FK, Midtvedt T, Hansen AK. Res Vet Sci. 2011 May 2
We hypothesized that antibiotic treatment in C57BL/6 mice would have an impact on glucose tolerance without affecting weight and gut immunology. When compared to mice treated with erythromycin or the controls, treatment for five weeks with ampicillin improved glucose tolerance without significantly affecting the weight or the number of gut mucosal regulatory T cells, tolerogenic dendritic cells or T helper cells type 1....

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Long-acting lipidated analogue of human pancreatic polypeptide is slowly released into circulation. Bellmann-Sickert K, Elling CE, Madsen AN, Little PB, Lundgren K, Gerlach LO, Bergmann R, Holst B, Schwartz TW, Beck-Sickinger AG. J Med Chem. 2011 Apr 28;54(8):2658-67
The main disadvantages of peptide pharmaceuticals are their rapid degradation and excretion, their low hydrophilicity, and low shelf lifes. These bottlenecks can be circumvented by acylation with fatty acids (lipidation) or polyethylene glycol (PEGylation). Here, we describe the modification of a human pancreatic polypeptide analogue specific for the human (h)Y(2) and hY(4) receptor with PEGs of different size and palmitic acid....

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Investigations of the human endocannabinoid system in two subcutaneous adipose tissue depots in lean subjects and in obese subjects before and after weight loss. Bennetzen MF, Wellner N, Ahmed SS, Ahmed SM, Diep TA, Hansen HS, Richelsen B, Pedersen SB. Int J Obes (Lond). 2011 Feb 15
Endocannabinoids (ECs) have a role in obesity by affecting appetite and through peripheral effects. Obesity is associated with a dysregulation of the endocannabinoid system (ECS). Objective: We aimed to determine the ECS in subcutaneous adipose tissue (AT) in obese subject and investigate the influence of diet-induced weight loss on this system....

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Dietary fat decreases intestinal levels of the anorectic lipids through a fat sensor. Diep TA, Madsen AN, Holst B, Kristiansen MM, Wellner N, Hansen SH, Hansen HS. FASEB J. 2011 Feb.
This study was undertaken to investigate the link between dietary fat content and intestinal levels of anorectic N-acylethanolamines (NAEs), including oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA).... 

 

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International Union of Basic and Clinical Pharmacology. LXXIX. Cannabinoid receptors and their ligands: beyond CB₁ and CB₂. Pertwee RG, Howlett AC, Abood ME, Alexander SP, Di Marzo V, Elphick MR, Greasley PJ, Hansen HS, Kunos G, Mackie K, Mechoulam R, Ross RA. Pharmacol Rev. 2010 Dec
This review summarizes current data indicating the extent to which cannabinoid receptor ligands undergo orthosteric or allosteric interactions with non-CB(1), non-CB(2) established GPCRs, deorphanized receptors such as GPR55, ligand-gated ion channels, transient receptor potential (TRP) channels, and other ion channels or peroxisome proliferator-activated nuclear receptors....

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Pitfalls in the sample preparation and analysis of N-acylethanolamines. Skonberg C, Artmann A, Cornett C, Hansen SH, Hansen HS. J.Lipid Res. 2010 Oct
N-acylethanolamines (NAEs) are a group of lipid mediators synthesized in response to a number of physiological and pathological stimuli. Because of the low tissue concentrations of NAEs, analyses often include liquid extraction followed by solid-phase extraction and subsequent quantitation by LC/MS or GC/MS. Reported levels of NAEs vary considerably, however, and often no explanation is given for these discrepancies....

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The emerging role of promiscuous 7TM receptors as chemosensors for food intake. Wellendorph P, Johansen LD, Bräuner-Osborne H. Vitam Horm. 2010
In recent years, several highly promiscuous seven transmembrane (7TM) receptors have been cloned and characterized of which many are activated broadly by amino acids, proteolytic degradation products, carbohydrates, or free fatty acids (FFAs) and are expressed in taste tissue, the gastrointestinal (GI) tract, endocrine glands, adipose tissue, and/or kidney. This has led to the hypothesis that these receptors may act as sensors of food intake modulating, for example, release of incretin hormones from the gut, insulin/glucagon from the pancreas, and leptin from adipose tissue....

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Dietary fat decreases intestinal levels of the anorectic lipids through a fat sensor. Diep TA, Madsen AN, Holst B, Kristiansen MM, Wellner N, Hansen SH, Hansen HS. 2010 Oct 19.
This study was undertaken to investigate the link between dietary fat content and intestinal levels of anorectic N-acylethanolamines (NAEs), including oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA). Male rats were fed high-fat diets (HFDs) with variable percentages of fat [20-45% of total energy (E%)] for 1-7 d; afterward, the jejunums were isolated, and jejunal NAE levels were measured by liquid-chromatography mass spectrometry....

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The endocannabinoid system and its relevance for nutrition. Maccarrone M, Gasperi V, Catani MV, Diep TA, Dainese E, Hansen HS, Avigliano L. Annu Rev Nutr. 2010 Aug
In this review, the main features of the ECS are summarized in order to put in better focus our current knowledge of the nutritional relevance of endocannabinoid signaling and of its role in obesity, cardiovascular pathologies, and gastrointestinal diseases. The central and peripheral pathways that underlie these effects are discussed, as well as the possible exploitation of ECS components as novel drug targets for therapeutic intervention in eating disorders....

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Palmitoylethanolamide and other anandamide congeners. Proposed role in the diseased brain. Hansen HS. Exp Neurol. 2010 Jul;224(1):48-55.
Acylethanolamides are formed in the brain "on demand" from membrane phospholipids called N-acylated phosphatidylethanolamines. The acylethanolamides are signaling molecules of lipid nature, and this lipofilicity suggests an autocrine function....

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Postprandial diabetic glucose tolerance is normalized by gastric bypass feeding as opposed to gastric feeding and is associated with exaggerated GLP-1 secretion: a case report. Dirksen C et al. Diabetes Care. 2010 Feb;33(2): 375-7.
OBJECTIVE: To examine after gastric bypass the effect of peroral versus gastroduodenal feeding on glucose metabolism.
RESEARCH DESIGN AND METHODS: A type 2 diabetic patient was examined on 2 consecutive days 5 weeks after gastric bypass. A standard liquid meal was given on the first day into the bypassed gastric remnant and on the second day perorally. Plasma glucose, insulin, C-peptide, glucagon, incretin hormones, peptide YY, and free fatty acids were measured....

 

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In vivo characterization of high Basal signaling from the ghrelin receptor. Petersen PS, Woldbye DP, Madsen AN, Egerod KL, Jin C, Lang M, Rasmussen M, Beck-Sickinger AG, Holst B. Endocrinology. 2009 Nov;150(11):4920-30. 
The receptor for the orexigenic peptide, ghrelin, is one of the most constitutively active 7TM receptors known, as demonstrated under in vitro conditions. Change in expression of a constitutively active receptor is associated with change in signaling independent of the endogenous ligand. In the following study, we found that the expression of the ghrelin receptor in the hypothalamus was up-regulated approximately 2-fold in rats both during 48-h fasting and by streptozotocin-induced hyperphagia....

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GPR39 deficiency is associated with pancreatic islet cell dysfunction. B.Holst, K.L.Egerod, C.Jin, P.S.Petersen, M.V.Østergaard, J.Hald, J.Størling, T.Mandrup-Poulsen, J.J.Holst, P.Thams, C.Ørskov. N.Wierup, F.Sundler, O.D.Madsen and T.W.Schwartz. Endocrinology 2009 150: 2577-85

 G protein-coupled receptor (GPR)-39 is a seven-transmembrane receptor expressed mainly in endocrine and metabolic tissues that acts as a Zn(++) sensor signaling mainly through the G(q) and G(12/13) pathways. The expression of GPR39 is regulated by hepatocyte nuclear factor (HNF)-1alpha and HNF-4alpha, and in the present study, we addressed the importance of GPR39 for glucose homeostasis and pancreatic islets function. The expression and localization of GPR39 were characterized in the endocrine pancreas and pancreatic cell lines....

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Reviews 

Effect of sibutramine on cardiovascular outcomes in over-weight and obese subjects. James WP et al. N Engl J Med. 2010 Sep 2;363(10):905-17.[Astrup and colleagues]
The long-term effects of sibutramine treatment on the rates of cardiovascular events and cardiovascular death among subjects at high cardiovascular risk have not been established. We enrolled in our study 10,744 overweight or obese subjects, 55 years of age or older, with preexisting cardiovascular disease, type 2 diabetes mellitus, or both to assess the cardiovascular consequences of weight management with and without sibutramine in subjects at high risk for cardiovascular events....

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The endocannabinoid system and its relevance for nutrition. Maccarrone M, Gasperi V, Catani MV, Diep TA, Dainese E, Hansen HS, Avigliano L. Annu Rev Nutr. 2010 Aug 21;30:423-40.
Endocannabinoids bind to cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. The biological actions of these polyunsaturated lipids are controlled by key agents responsible for their synthesis, transport and degradation, which together form an endocannabinoid system (ECS). In the past few years, evidence has been accumulated for a role of the ECS in regulating food intake and energy balance, both centrally and peripherally....

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The emerging role of promiscuous 7TM receptors as chemosensors for food intake. Wellendorph P, Johansen LD, Bräuner-Osborne H. Vitam Horm. 2010
In recent years, several highly promiscuous seven transmembrane (7TM) receptors have been cloned and characterized of which many are activated broadly by amino acids, proteolytic degradation products, carbohydrates, or free fatty acids (FFAs) and are expressed in taste tissue, the gastrointestinal (GI) tract, endocrine glands, adipose tissue, and/or kidney....

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Preproglucagon derived peptides GLP-1, GLP-2 and oxyntomodulin in the CNS: Role of peripherally secreted and centrally produced peptides. Vrang N, Larsen PJ. Prog Neurobiol. 2010 Jul 16. PMID: 20638440.
The scientific understanding of preproglucagon derived peptides has provided people with type 2 diabetes with two novel classes of glucose lowering agents, the dipeptidyl peptidase IV (DPP-IV) inhibitors and GLP-1 receptor agonists. For the scientists, the novel GLP-1 agonists, and DPP-IV inhibitors have evolved as useful tools to understand the role of the preproglucagon derived peptides in normal physiology and disease....

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Glucagon and glucagon-like peptides 1 and 2. Holst JJ; Results Probl Cell Differ. 2010;50:121-35.
The glucagon gene is expressed not only in the alpha cells of the pancreatic islets but also in the endocrine cells of the intestinal epithelium (so-called L-cells), and in certain neurons of the brain stem....

 

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An enteroendocrine full package solution. Schwartz TW, Holst B.;Cell Metab. 2010 Jun 9;11(6):532-42.(see figure below)
The regulatory repertoire of the enteroendocrine L cell is now supplemented by Cox et al. (2010) with a two-way paracrine loop to the neighboring enterocytes. A picture of a close local interplay in the intestine between lipid and peptide messenger systems, both exploiting paracrine, endocrine, and neuronal pathways, is emerging....

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Til toppenFitness and Muscle theme

Original papers

Three months of strictly controlled daily endurance exercise reduces thrombin generation and fibrinolytic risk markers in younger moderately overweight men. Gram AS, Bladbjerg EM, Skov J, Ploug T, Sjödin A, Rosenkilde M, Madsen DE, Stallknecht BM. Eur J Appl Physiol. 2015 Jun. Physical activity is associated with a decreased risk of cardiovascular disease, but dose dependency of long-term physical exercise on biomarkers within coagulation and fibrinolysis is unknown. We aimed to investigate effects of two doses of daily endurance exercise on biomarkers of the haemostatic balance in overweight men. Our results demonstrate an effect of 3 months of daily endurance exercise on biomarkers of the haemostatic balance in the direction of reduced cardiovascular risk, independent of exercise dose.

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Six weeks' aerobic retraining after two weeks' immobilization restores leg lean mass and aerobic capacity but does not fully rehabilitate leg strenght in young and older men. Vigelsø A, Gram M, Wiuff C, Andersen JL, Helge JW, Dela F. J Rehabil Med. 2015 Apr. OBJECTIVE: To determine the effect of aerobic retraining as rehabilitation after short-term leg immobilization on leg strength, leg work capacity, leg lean mass, leg muscle fibre type composition and leg capillary supply, in young and older men. CONCLUSION: Short-term leg immobilization had marked effects on leg strength, and work capacity and 6 weeks' retraining was sufficient to increase, but not completely rehabilitate, muscle strength, and to rehabilitate aerobic work capacity and leg lean mass (in the young men).

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A novel method for determining human ex vivo submaximal skeletal muscle mitochondrial function. Hey-Mogensen M, Gram M, Jensen MB, Lund MT, Jensen CN, Scheibye-Knudsen M, Bohr VA, Dela F (2015). J. Physiol (in press)

Independent effects of endurance training and weight loss on peak fat oxidation in moderately overweight men: a randomized controlled trial. Nordby P, Rosenkilde M, Ploug T, Westh K, Feigh M, Nielsen NB, Helge JW, Stallknecht B. J Appl Physiol (1985). 2015 Apr. Endurance training increases peak fat oxidation (PFO) during exercise, but whether this is independent of changes in body weight is not known. The aim of the present study was to investigate the effects of endurance training with or without weight loss or a diet-induced weight loss on PFO and on key skeletal muscle mitochondrial proteins involved in fat oxidation.

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Skeletal muscle mitochondrial H2O2 emission increases with immobilization and decreases after aerobic training in young and older men. Gram M , Vigelso A, Yokota T, Dela F, Hey-Mogensen M (2015) J. Physiol (in press)

GAPDH and β-actin protein decreases with aging, making Stain-Free technology a superior loading control in Western blotting of human skeletal muscle. Vigelsø A, Dybboe R, Hansen CN, Dela F, Helge JW, Guadalupe Grau A. J Appl Physiol (1985). 2015 Feb 1;118(3):386-94. Reference proteins (RP) or the total protein (TP) loaded is used to correct for uneven loading and/or transfer in Western blotting. However, the signal sensitivity and the influence of physiological conditions may question the normalization methods. Therefore, three widely used reference proteins [β-actin, glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and α-tubulin], as well as TP loaded measured by Stain-Free technology (SF) as normalization tool were tested.

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The Effect of Reduced Physical Activity and Retraining on Blood Lipids and Body Composition in Young and Older Adult Men. Nørregaard J, Gram M, Vigelsoe A, Wiuff C, Kuhlman AB, Helge JW, Dela F. J Aging Phys Act. 2014 Nov. We studied the effect of physical inactivity and subsequent re-training on cardiovascular risk factors in seventeen young (Y; 23.4±0.5) and fifteen older adult (O; 68.1±1.1 yrs.) men who underwent 14 days of one leg immobilization followed by six weeks of training. Body weight remained unchanged. Daily physical activity decreased by 31±9 (Y) and 37±9 (O) % (P<0.001). Maximal oxygen uptake decreased with inactivity (Y) and always increased with training. Visceral fat mass decreased (P<0.05) with training. Concentrations of lipids in blood were always highest in the older adults. FFA and glycerol increased with reduced activity (P<0.05), but reverted with training. Training resulted in increases in HDL-C (P<0.05) and a decrease in LDL-C and TC:HDL-C ratio (P<0.05). A minor reduction in daily physical activity for two weeks increases blood lipids in both Y and O men. Six weeks of training improved blood lipids along with loss of visceral fat.

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Two weeks of one-leg immobilization decreases skeletal muscle respiratory capacity equally in young and elderly men. Gram M, Vigelsø A, Yokota T, Hansen CN, Helge JW, Hey-Mogensen M, Dela F. Exp Gerontol. 2014 Oct;58:269-78. Physical inactivity affects human skeletal muscle mitochondrial oxidative capacity but the influence of aging combined with physical inactivity is not known. This study investigates the effect of two weeks of immobilization followed by six weeks of supervised cycle training on muscle oxidative capacity in 17 young (23±1years) and 15 elderly (68±1years) healthy men.

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Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release. Jensen TE, Sylow L, Rose AJ, Madsen AB, Angin Y, Maarbjerg SJ and Richter EA. Molecular Metabolism 2014. This review summarizes the evidence supporting the Ca2+ feed-forward paradigm and its proposed signaling links to glucose transport regulation in skeletal muscle and other cell types. The literature is contrasted against our recent findings suggesting that SR Ca2+ release is neither essential nor adequate to stimulate muscle glucose transport. Instead, feedback signals through AMPK and mechanical stress are likely to account for most of contraction-stimulated glucose transport.

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Acute mTOR inhibition induces insulin resistance and alters substrate utilization. Kleinert M, Sylow L, Fazakerley DJ, Krycer JR, Thomas KC, Oxboll AJ, Jordy AB, Jensen TE, Yang G, Schjerling P, Kiens B, James DE, Ruegg MA and Richter EA. Mol Metab 3: 630-641, 2014. The effect of acute inhibition of both mTORC1 and mTORC2 on metabolism is unknown. A single injection of the mTOR kinase inhibitor, AZD8055, induced a transient, yet marked increase in fat oxidation and insulin resistance in mice, whereas the mTORC1 inhibitor rapamycin had no effect.

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The relationship between skeletal muscle mitochondrial citrate synthase activity and whole body oxygen uptake adaptations in response to exercise training. Vigelsø A*, Andersen NB*, Dela F. Int J Physiol Pathophysiol Pharmacol. 12;6(2):84-101, 2014. Citrate synthase (CS) activity is a validated biomarker for mitochondrial density in skeletal muscle. CS activity is also used as a biochemical marker of the skeletal muscle oxidative adaptation to a training intervention, and a relationship between changes in whole body aerobic capacity and changes in CS activity is often assumed. However, this relationship and absolute values of CS and maximal oxygen uptake (V.O2max) has never been assessed across different studies. A systematic PubMed search on literature published from 1983 to 2013 was performed.

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Physical inactivity and muscle oxidative capacity in humans. Gram, M., R. Dahl, and F. Dela. Eur J Sport Sci, 2014. 14(4): p. 376-83. Physical inactivity is associated with a high prevalence of type 2 diabetes and is an independent predictor of mortality. It is possible that the detrimental effects of physical inactivity are mediated through a lack of adequate muscle oxidative capacity. This short review will cover the present literature on the effects of different models of inactivity on muscle oxidative capacity in humans.

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The effect of high-intensity training on mitochondrial fat oxidation in skeletal muscle and subcutaneous adipose tissue. Larsen S, Danielsen JH, Sondergard SD, Sogaard D, Vigelsø A, Dybboe R, Skaaby S, Dela F, and Helge JW. Scandinavian journal of medicine & science in sports 2014. Scand J Med Sci Sports May 2014.  High-intensity interval training (HIT) is known to increase mitochondrial content in a similar way as endurance training [60-90% of maximal oxygen uptake (VO2peak )]. Whether HIT increases the mitochondria's ability to oxidize lipids is currently debated. We investigated the effect of HIT on mitochondrial fat oxidation in skeletal muscle and adipose tissue.

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Biomarkers of coagulation, fibrinolysis, endothelial function, and inflammation in arterialized venous blood. Gram, A.S., Skov, J., Ploug, T., Sidelmann, J.J., Stallknecht, B.M. and Bladbjerg, E.M. Blood Coagul Fibrinolysis. 2014 Jan 14. Effects of venous blood arterialization on cardiovascular risk markers are still unknown. We evaluated biomarkers of inflammation, coagulation, fibrinolysis, and endothelial function in arterialized compared with regular venous blood. Cubital venipunctures were obtained from 10 healthy volunteers.

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Calibrated Image Derived Input Functions for the Determination of the Metabolic Uptake Rate of Glucose with [18F]-FDG PET. Christensen, A.N., Reichkendler, M.H., Larsen, R., Auerbach, P.L., Hoejgaard, L., Nielsen, H.B., Ploug, T., Stallknecht, B. and Holm, S. Nucl Med Commun. 2014 Apr. We investigated the use of a simple calibration method to remove bias in previously proposed approaches to image-derived input functions (IDIFs) when used to calculate the metabolic uptake rate of glucose (K(m)) from dynamic [(18)F]-FDG PET scans of the thigh. Our objective was to obtain nonbiased, low-variance K(m) values without blood sampling.

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The effect of immobilization on exercise-induced interleukin-6 and tumor necrosis factor-&[alpha] release from the leg. Reihmane, D., Hansen A.V., Gram M., Kuhlman A.B., Nørregaard J., Pedersen H.P., Helge J.W., and Dela F. ExpPhysiol;98: 778-783, 2013.

Human skeletal muscle perilipin 2 and 3 expression varies with insulin sensitivity. Vigelsø A, Prats C, Ploug T, Dela F, and Helge JW. Journal of Biomedical Science and Engineering, 2013 6: 65-72. 

Changes in peak fat oxidation in response to different doses of endurance training. Rosenkilde, M., Reichkendler, M.H., Auerbach, P., Bonne, T.C., Sjödin, A., Ploug, T. and Stallknecht, B. Scand J Med Sci Sports. 2013 Dec 18. The effect of different doses of endurance training on the capacity to oxidize fat during exercise in sedentary, overweight men and assessment of variables associated with changes in peak fat oxidation (PFO) were evaluated. 

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Careful science? Bodywork and care practices in randomised clinical trials. Jespersen AP, Bønnelycke J and Eriksen HH. Sociology of Health and Illness, Nov 6, 2013. This article is based on our participation in FINE, a multidisciplinary Danish research project. The core methodology of FINE was a randomised controlled trial in which 61 moderately overweight men were put into different exercise groups. In this article we analyse the scientific work of the trial as representing entangled processes of bodywork, where data are extracted and objectified bodies are manipulated and care practices address the emotional, social and mundane aspects of the participants' everyday lives.

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Endotrophin Triggers Adipose Tissue Fibrosis, Inflammation and Metabolic Dysfunction. Sun, K., Park, J., Gupta, O., Holland, W.L., Auerbach, P.L., Zhang, N., Marangoni, R.G., Nicoloro, S.M., Czech, M.P., Varga, J., Ploug, T., An, Z. and Scherer, P. E. Nat Commun. 2014 Mar 19. We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonstrate that endotrophin plays a pivotal role in shaping a metabolically unfavourable microenvironment in adipose tissue during consumption of a high-fat diet (HFD). 

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Dose-response effects of endurance training on plasma adiponectin multimers in younger, moderately overweight men. Stallknecht, B., Auerbach, P.L., Reichkendler, M.H., Rosenkilde, M., Sjödin, A. and Ploug, T. Am J Physiol Regul Integr Comp Physiol. 2013 Sep. Regular physical exercise decreases overall morbidity in obese subjects, which may be due to modulations of inflammatory pathways. In this randomized clinical trial we investigated the separate effects of endurance training-induced weight loss, diet-induced weight loss, and endurance training per se (without weight loss) on plasma adiponectin multimer composition (Western blotting) and adipose tissue macrophage content (immunohistochemistry) in young, moderately overweight men.

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Impairments in Site-Specific AS160 Phosphorylation and Effects of Exercise Training. Consitt LA, Van Meter J, Newton CA, Collier DN, Dar MS, Wojtaszewski JF, Treebak JT, Tanner CJ, Houmard JA. Diabetes. 2013 Oct.
The purpose of this study was to determine if site-specific phosphorylation at the level of Akt substrate of 160 kDa (AS160) is altered in skeletal muscle from sedentary humans across a wide range of the adult life span (18-84 years of age) and if endurance- and/or strength-oriented exercise training could rescue decrements in insulin action and skeletal muscle AS160 phosphorylation...

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Appetite regulation in overweight, sedentary men after different amounts of endurance exercise - a randomized controlled trial. Rosenkilde M, Reichkendler MH, Auerbach P, Toräng S, Gram AS, Ploug T, Holst JJ, Sjödin A, Stallknecht BM. J Appl Physiol (1985). 2013 Sep.
Weight loss induced by endurance exercise is often disappointing, possibly due to a increase in energy intake mediated through greater appetite. The aim of this study was to evaluate fasting, postprandial and post-exercise appetite regulation after an intervention prescribing two amounts of endurance exercise...

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Compliance with physical exercise: Using a multidisciplinary approach within a dose-dependent exercise study of moderately overweight men. Gram AS, Bønnelycke J, Rosenkilde M, Reichkendler M, Auerbach P, Sjödin A, Ploug T, Jespersen A, Stallknecht B. Scand J Public Health. 2013 Sep.
Aims: Sixty-one healthy, sedentary, moderately overweight young men participated in a randomised controlled trial to examine the effects of two different doses of endurance exercise on health behaviour and exercise compliance. Methods: Participants were randomised to a sedentary control group, a moderate (MOD; 300 kcal/day) or a high-dose (HIGH; 600 kcal/day) endurance exercise group for 12 weeks...

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Exercise training favors increased insulin-stimulated glucose uptake in skeletal muscle in contrast to adipose tissue: A randomized study using FDG PET imaging. Reichkendler, M., P. Auerbach, M. Rosenkilde, A. Christensen, S. Holm, M.B. Petersen, A. Lagerberg, H. Larsson, E. Rostrup, T. Mosbech, A. Sjödin, A. Kjær, T. Ploug, L. Højgaard, and B.M. Stallknecht. Am.J.Physiol.Endocrinol.Metab., Aug 2013. We investigated the effect of aerobic exercise training on insulin-stimulated glucose uptake in five individual femoral muscle groups and four different adipose tissue regions using dynamic (femoral region) and static (abdominal region) 2-deoxy-2-(18F)fluoro-D-glucose (FDG) PET/CT methodology during steady state insulin infusion (40 mU*m-2*min-1)...

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Differential effects of endurance training and weight loss on plasma adiponectin multimers and adipose tissue macrophages in younger, moderately overweight men. Auerbach, P., P. Nordby, L.Q. Bendtsen, J.L. Mehlsen, S.K. Basnet, H. Vestergaard, T. Ploug, and B.M. Stallknecht. Am.J.Physiol.Regul.Integr.Comp.Physiol., Sep. 2013. In this randomized clinical trial we investigated the separate effects of endurance training-induced weight loss, diet-induced weight loss and endurance training per se (without weight loss) on plasma adiponectin multimer composition (Western blotting) and adipose tissue macrophage content (immunohistochemistry) in young, moderately overweight men. Weight loss and endurance training per se decreased whole body fat percentage in an additive manner...

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Exercise, GLUT4, and skeletal muscle glucose uptake. Richter EA, Hargreaves M. Physiol Rev. 2013 Jul.
Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporter which translocates from intracellular storage depots to the plasma membrane and T-tubules upon muscle contraction...

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Effect of birth weight and 12 weeks of exercise training on exercise-induced AMPK signaling in human skeletal muscle. Mortensen B, Hingst JR, Frederiksen N, Hansen RW, Christiansen CS, Iversen N, Friedrichsen M, Birk JB, Pilegaard H, Hellsten Y, Vaag A, Wojtaszewski JF. Am J Physiol Endocrinol Metab. 2013 Jun.
Subjects with a low birth weight (LBW) display increased risk of developing type 2 diabetes (T2D). We hypothesized that this is associated with defects in muscle adaptations following acute and regular physical activity, evident by impairments in the exercise-induced activation of AMPK signaling...

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Rac1 signaling is required for insulin-stimulated glucose uptake and is dysregulated in insulin-resistant murine and human skeletal muscle. Sylow L, Jensen TE, Kleinert M, Højlund K, Kiens B, Wojtaszewski J, Prats C, Schjerling P, Richter EA. Diabetes. 2013 Jun.
The actin cytoskeleton-regulating GTPase Rac1 is required for insulin-stimulated GLUT4 translocation in cultured muscle cells. However, involvement of Rac1 and its downstream signaling in glucose transport in insulin-sensitive and insulin-resistant mature skeletal muscle has not previously been investigated...

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AMPK and insulin action--responses to ageing and high fat diet. Frøsig C, Jensen TE, Jeppesen J, Pehmøller C, Treebak JT, Maarbjerg SJ, Kristensen JM, Sylow L, Alsted TJ, Schjerling P, Kiens B, Wojtaszewski JF, Richter EA. PLoS One. 2013 May
The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact role of AMPK is not well understood...

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LKB1 regulates lipid oxidation during exercise independently of AMPK. Jeppesen J, Maarbjerg SJ, Jordy AB, Fritzen AM, Pehmøller C, Sylow L, Serup AK, Jessen N, Thorsen K, Prats C, Qvortrup K, Dyck JR, Hunter RW, Sakamoto K, Thomson DM, Schjerling P, Wojtaszewski JF, Richter EA, Kiens B. Diabetes. 2013 May.
Lipid metabolism is important for health and insulin action, yet the fundamental process of regulating lipid metabolism during muscle contraction is incompletely understood. Here, we show that liver kinase B1 (LKB1) muscle-specific knockout (LKB1 MKO) mice display decreased fatty acid (FA) oxidation during treadmill exercise...

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Rac1 is a novel regulator of contraction-stimulated glucose uptake in skeletal muscle. Sylow L, Jensen TE, Kleinert M, Mouatt JR, Maarbjerg SJ, Jeppesen J, Prats C, Chiu TT, Boguslavsky S, Klip A, Schjerling P, Richter EA. Diabetes. 2013 Apr.
In skeletal muscle, the actin cytoskeleton-regulating GTPase, Rac1, is necessary for insulin-dependent GLUT4 translocation. Muscle contraction increases glucose transport and represents an alternative signaling pathway to insulin...

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Akt2 influences glycogen synthase activity in human skeletal muscle through regulation of NH₂-terminal (sites 2 + 2a) phosphorylation. Friedrichsen M, Birk JB, Richter EA, Ribel-Madsen R, Pehmøller C, Hansen BF, Beck-Nielsen H, Hirshman MF, Goodyear LJ, Vaag A, Poulsen P, Wojtaszewski JF. Am J Physiol Endocrinol Metab. 2013 Mar.
Type 2 diabetes is characterized by reduced muscle glycogen synthesis. The key enzyme in this process, glycogen synthase (GS), is activated via proximal insulin signaling, but the exact molecular events remain unknown. Previously, we demonstrated that phosphorylation of Thr³⁰⁸ on Akt (p-Akt-Thr³⁰⁸), Akt2 activity, and GS activity in muscle were positively associated with insulin sensitivity...

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Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation, and ceramide content in skeletal muscles of men but not women. Høeg LD, Sjøberg KA, Lundsgaard AM, Jordy AB, Hiscock N, Wojtaszewski JF, Richter EA, Kiens B. J Appl Physiol (1985). 2013 Mar.
Adiponectin is an adipokine that regulates metabolism and increases insulin sensitivity. Mechanisms behind this insulin-sensitizing effect have been investigated in rodents, but little is known in humans, especially in skeletal muscle. Women have higher serum concentrations of adiponectin than men and are generally more insulin sensitive in skeletal muscle than men...

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Exercise-induced AMPK activity in skeletal muscle: role in glucose uptake and insulin sensitivity. Friedrichsen M, Mortensen B, Pehmøller C, Birk JB, Wojtaszewski JF. Mol Cell Endocrinol. 2013 Feb.
The energy/fuel sensor 5'-AMP-activated protein kinase (AMPK) is viewed as a master regulator of cellular energy balance due to its many roles in glucose, lipid, and protein metabolism...

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Immobilisation increases interleukin-6, but not tumor necrosis factor-α, release from the leg during exercise in humans. Reihmane D, Hansen AV, Gram M, Kuhlman AB, Norregaard J, Pedersen HP, Lund MT, Helge JW and Dela F. Exp Physiol. 2013 Jan 18. [Epub ahead of print]
Data on interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) release during acute exercise are not conclusive and lack information about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL-6 and TNF-α release during exercise. We have now studied the temporal relationship of leg IL-6 and TNF-α release before and during ...

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Two weeks of metformin treatment enhances mitochondrial respiration in skeletal muscle of AMPK kinase dead but not wild type mice. Kristensen JM, Larsen S, Helge JW, Dela F, Wojtaszewski JF. PLoS One. 2013.
Metformin is used as an anti-diabetic drug. Metformin ameliorates insulin resistance by improving insulin sensitivity in liver and skeletal muscle. Reduced mitochondrial content has been reported in type 2 diabetic muscles and it may contribute to decreased insulin sensitivity characteristic for diabetic muscles...

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EMG-normalised kinase activation during exercise is higher in human gastrocnemius compared to soleus muscle. Jensen TE, Leutert R, Rasmussen ST, Mouatt JR, Christiansen ML, Jensen BR, Richter EA. PLoS One. 2012.
In mice, certain proteins show a highly confined expression in specific muscle groups. Also, resting and exercise/contraction-induced phosphorylation responses are higher in rat skeletal muscle with low mitochondrial content compared to muscles with high mitochondrial content, possibly related to differential reactive oxygen species (ROS)-scavenging ability or resting glycogen content...

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Enhanced fatty acid oxidation and FATP4 protein expression after endurance exercise training in human skeletal muscle. Jeppesen J, Jordy AB, Sjøberg KA, Füllekrug J, Stahl A, Nybo L, Kiens B. PLoS One. 2012.
FATP1 and FATP4 appear to be important for the cellular uptake and handling of long chain fatty acids (LCFA). These findings were obtained from loss- or gain of function models. However, reports on FATP1 and FATP4 in human skeletal muscle are limited. Aerobic training enhances lipid oxidation; however, it is not known whether this involves up-regulation of FATP1 and FATP4 protein...

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Only minor metabolic health benefits of high as opposed to moderate dose physical exercise in young, moderately overweight men. M H Reichkendler, M Rosenkilde, P L Auerbach, J Agerschou, M B Nielsen, A Kjaer, L Hoejgaard, A Sjödin, T Ploug and B Stallknecht. Obesity, 2012 Dec
Objective: To examine the dose-response effects of exercise training on insulin sensitivity, metabolic risk and quality of life. Design and methods: Sixty-one healthy, sedentary (VO2max: 35±5 mL/kg/min), moderately overweight (BMI: 27.9±1.8), young (age: 29±6 yrs) men were randomized to sedentary living (CON; n=18), moderate (MOD; 300 kcal/day, n=21) or high (HIGH; 600 kcal/day, n=22) dose physical exercise for 11 weeks. Results: The return rate for post intervention ...

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Exercise Alleviates Lipid-Induced Insulin Resistance in Human Skeletal Muscle-Signaling Interaction at the Level of TBC1 Domain Family Member 4. Pehmøller C, Brandt N, Birk JB, Høeg LD, Sjøberg KA, Goodyear LJ, Kiens B, Richter EA, Wojtaszewski JF. Diabetes. 2012 Nov
Excess lipid availability causes insulin resistance. We examined the effect of acute exercise on lipid-induced insulin resistance and TBC1 domain family member 1/4 (TBCD1/4)-related signaling in skeletal muscle. In eight healthy young male subjects, 1 h of one-legged knee-extensor exercise was followed by 7 h of saline or intralipid infusion....

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Effect of Different Doses of Exercise on Sleep Duration, Sleep Efficiency and Sleep Quality in Sedentary, Overweight Men. Jonas S. Kjeldsen, Mads Rosenkilde, Signe W. Nielsen, Michala Reichkendler, Pernille Auerbach, Thorkil Ploug, Bente Stallknecht, Anders M. Sjödin and Jean-Philippe Chaput. Bioenergetics. 2012 Oct
Objective: To evaluate the dose-response on aerobic exercise on sleep duration, sleep efficiency and sleep quality in previously sedentary, moderately overweight men. Methods: In a randomized, controlled trial, 53 sedentary Caucasian men aged between 20 and 40 years...

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Body fat loss and compensatory mechanisms in response to different doses of aerobic exercise--a randomized controlled trial in overweight sedentary males. Rosenkilde M, Auerbach P, Reichkendler MH, Ploug T, Stallknecht BM, Sjödin A. Am J Physiol Regul Integr Comp Physiol. 2012 Sep
The amount of weight loss induced by exercise is often disappointing. A diet-induced negative energy balance triggers compensatory mechanisms, e.g., lower metabolic rate and increased appetite. However, knowledge about potential compensatory mechanisms triggered by increased aerobic exercise is limited....

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Changes in insulin sensitivity precede changes in body composition during 14 days of step reduction combined with overfeeding in healthy young men. Knudsen SH, Hansen LS, Pedersen M, Dejgaard T, Hansen J, Hall GV, Thomsen C, Solomon TP, Pedersen BK, Krogh-Madsen R. J Appl Physiol. 2012 Jul
A lifestyle characterized by inactivity and a high-calorie diet is a known risk factor for impaired insulin sensitivity and development of Type 2 diabetes mellitus. To investigate possible links, nine young healthy men (24 ± 3 yr; body mass index of 21.6 ± 2.5 kg/m(2)) completed 14 days of step reduction (10,000 to 1,500 steps/day) and overfeeding (+50% kcal)....

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Mechanisms of improved glycaemic control after Roux-en-Y gastric bypass. Dirksen C, Jørgensen NB, Bojsen-Møller KN, Jacobsen SH, Hansen DL, Worm D, Holst JJ, Madsbad S. Diabetologia. 2012
Roux-en-Y gastric bypass (RYGB) greatly improves glycaemic control in morbidly obese patients with type 2 diabetes, in many even before significant weight loss. Understanding the responsible mechanisms may contribute to our knowledge of the pathophysiology of type 2 diabetes and help identify new drug targets or improve surgical techniques....

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Hyperglycaemia normalises insulin action on glucose metabolism but not the impaired activation of AKT and glycogen synthase in the skeletal muscle of patients with type 2 diabetes.Vind BF, Birk JB, Vienberg SG, Andersen B, Beck-Nielsen H, Wojtaszewski JF, Højlund K.Diabetologia. 2012 May
In type 2 diabetes, reduced insulin-stimulated glucose disposal, primarily glycogen synthesis, is associated with defective insulin activation of glycogen synthase (GS) in skeletal muscle. Hyperglycaemia may compensate for these defects, but to what extent it involves improved insulin signalling to glycogen synthesis remains to be clarified.... 

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GLUT4 and Glycogen Synthase Are Key Players in Bed Rest-Induced Insulin Resistance. Biensø RS, Ringholm S, Kiilerich K, Aachmann-Andersen NJ, Krogh-Madsen R, Guerra B, Plomgaard P, van Hall G, Treebak JT, Saltin B, Lundby C, Calbet JA, Pilegaard H, Wojtaszewski JF. Diabetes. 2012 May
To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both legs before and after a 3-h hyperinsulinemic euglycemic clamp performed 3 h after a 45-min, one-legged exercise. Blood samples were obtained from one femoral artery and both femoral veins before and during the clamp....

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Effects of lipopolysaccharide infusion on arterial levels and transcerebral exchange kinetics of glutamate and glycine in healthy humans. Ronan M. G. Berg,Sarah Taudorf, Damian M. Bailey, Carsten Lundby, Fin S. Larsen, Bente K. Pedersen, Kirsten Møller. Article first published online: 11 APR 2012

An imbalance between glutamate and glycine signalling may contribute to sepsis-associated encephalopathy by causing neuronal excitotoxicity. In this study, we therefore investigated the transcerebral exchange kinetics of glutamate and glycine in a human-experimental model of systemic inflammation.... 

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Muscle-derived expression of the chemokine CXCL1 attenuates diet-induced obesity and improves fatty acid oxidation in the muscle. Pedersen L, Olsen CH, Pedersen BK, Hojman P. Am J Physiol Endocrinol Metab. 2012 Apr.
Serum levels and muscle expression of the chemokine CXCL1 increase markedly in response to exercise in mice. Because several studies have established muscle-derived factors as important contributors of metabolic effects of exercise, this study aimed at investigating the effect of increased expression of muscle-derived CXCL1 on systemic and intramuscular metabolic parameters, with focus on fatty acid oxidation and oxidative metabolism in skeletal muscle....

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Endurance Training Per Se Increases Metabolic Health in Young, Moderately Overweight Men. Nordby P, Auerbach PL, Rosenkilde M, Kristiansen L, Thomasen JR, Rygaard L, Groth R, Brandt N, Helge JW, Richter EA, Ploug T, Stallknecht B. Obesity (Silver Spring). 2012 Mar 22.
Health benefits of physical activity may depend on a concomitant weight loss. In a randomized, controlled trial, we compared the effects of endurance training with or without weight loss to the effect of weight loss induced by an energy-reduced diet in 48 sedentary, moderately overweight men who completed a 12-week intervention program of training (T), energy-reduced diet (D), training and increased diet (T-iD), or control (C)....

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Regulation and limitations to fatty acid oxidation during exercise. Jacob Jeppesen, Bente Kiens. The Journal of Physiology, Volume 590, Issue 5, March 2012.
Fatty acids (FAs) as fuel for energy utilization during exercise originate from different sources: FAs transported in the circulation either bound to albumin or as triacylglycerol (TG) carried by very low density lipoproteins and FAs from lipolysis of muscle TG stores. Despite a high rate of energy expenditure during high intensity exercise the total FA oxidation is suppressed to below that observed during moderate intensity exercise. Although this has been known for many years, the mechanisms behind this phenomenon are still not fully elucidated....

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Kroppe i laboratoriet. Individuelle kroppe, forsøgskroppe og samfundskroppe i kliniske forsøg med overvægt. Astrid Pernille Jespersen. Kulturstudier 2011
In the last years a lot has been said and written about a global epidemic of obesity. In Denmark alone, between 30 and 40 per cent of the adult population is estimated to be overweight or obese. Obesity is regarded as one of the major threats to the health of populations, and it ranks high on the agenda of both politicians and researchers. The present article describes a clinical trial with moderately overweight, inactive males, who, through a twelve week intervention period, were prescribed a training schedule of 0, 30 and 60 minutes per day respectively....

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Regulation of glucose and glycogen metabolism during and after exercise. Jensen TE, Richter EA. J Physiol. 2012 Mar 1;590(Pt 5):1069-76. Epub 2011 Dec 23.
Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport is increased in the contracting muscle followed by a discussion of glycogen mobilization and synthesis by the action of glycogen phosphorylase and glycogen synthase, respectively....

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Increased shelterin mRNA expression in peripheral blood mononuclear cells and skeletal muscle following an ultra-long-distance running event. Laye MJ, Solomon TP, Karstoft K, Pedersen KK, Nielsen SD, Pedersen BK. J Appl Physiol. 2012 Mar;112(5):773-81. Epub 2011 Dec 8.
Located at the end of chromosomes, telomeres are progressively shortened with each replication of DNA during aging. Integral to the regulation of telomere length is a group of proteins making up the shelterin complex, whose tissue-specific function during physiological stress is not well understood. In this study, we examine the mRNA and protein levels of proteins within and associated with the shelterin complex in subjects (n = 8, mean age = 44 yr) who completed a physiological stress of seven marathons in 7 days....

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Regulation and limitations to fatty acid oxidation during exercise. Jeppesen J, Kiens B. J Physiol. 2012 Mar 1;590(Pt 5):1059-68. Epub 2012 Jan 23.
Fatty acids (FAs) as fuel for energy utilization during exercise originate from different sources: FAs transported in the circulation either bound to albumin or as triacylglycerol (TG) carried by very low density lipoproteins and FAs from lipolysis of muscle TG stores. Despite a high rate of energy expenditure during high intensity exercise the total FA oxidation is suppressed to below that observed during moderate intensity exercise.... 

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Skeletal muscle PGC-1α is required for maintaining an acute LPS-induced TNFα response.Olesen J, Larsson S, Iversen N, Yousafzai S, Hellsten Y, Pilegaard H.PLoS One. 2012;7(2):e32222. Epub 2012 Feb 27.  
Many lifestyle-related diseases are associated with low-grade inflammation and peroxisome proliferator activated receptor γ coactivator (PGC)-1α has been suggested to be protective against low-grade inflammation. However, whether these anti-inflammatory properties affect acute inflammation is not known. The aim of the present study was therefore to investigate the role of muscle PGC-1α in acute inflammation....

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Role of PGC-1α in exercise and fasting-induced adaptations in mouse liver.
Haase TN, Ringholm S, Leick L, Biensø¸ RS, Kiilerich K, Johansen S, Nielsen MM, Wojtaszewski JF, Hidalgo J, Pedersen PA, Pilegaard H. Am J Physiol Regul Integr Comp Physiol. 2011 Nov.
The transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-γ coactivator (PGC)-1α plays a role in regulation of several metabolic pathways. By use of whole body PGC-1α knockout (KO) mice, we investigated the role of PGC-1α in fasting, acute exercise and exercise training-induced regulation of key proteins in gluconeogenesis and metabolism in the liver....

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Insulin Resistance after a 72 hour Fast is Associated with Impaired AS160 Phosphorylation and Accumulation of Lipid and Glycogen in Human Skeletal Muscle. Vendelbo MH, Clasen BF, Treebak JT, Møller L, Krusenstjerna-Hafstrøm T, Madsen M, Nielsen TS, Stødkilde-Jørgensen H, Pedersen SB, Jørgensen JO, Goodyear LJ, Wojtaszewski JF, Møller N, Jessen N. Am J Physiol Endocrinol Metab. 2011 Oct 25.
During fasting human skeletal muscle depends on lipid oxidation for its energy substrate metabolism. This is associated with the development of insulin resistance and a subsequent reduction of insulin-stimulated glucose uptake. The underlying mechanisms controlling insulin action on skeletal muscle under these conditions are unresolved. In a randomized design, we investigated 8 healthy subjects after a 72 hour fast as compared to a 10 hour overnight fast....

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Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle. Ringholm S, Biensø RS, Kiilerich K, Guadalupe-Grau A, Aachmann-Andersen NJ, Saltin B, Plomgaard P, Lundby C, Wojtaszewski JF, Calbet JA, Pilegaard H. Am J Physiol Endocrinol Metab. 2011 Oct
The aim was to test the hypothesis that 7 days of bed rest reduces mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after bed rest....

 

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Factors regulating fat oxidation in human skeletal muscle. Kiens B, Alsted TJ, Jeppesen J. Obes Rev. 2011 Oct
In modern societies, oversupply of calories leads to obesity and chronic metabolic stress, which may lead to development of disease. Oversupply of calories is often associated with elevated plasma lipid concentrations and accumulation of lipids in skeletal muscle leading to decreased insulin sensitivity. Consequently, enhanced fat oxidation might be beneficial in counteracting lipid accumulation....

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AMP-activated protein kinase (AMPK) beta1beta2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. O'Neill HM, Maarbjerg SJ, Crane JD, Jeppesen J, Jørgensen SB, Schertzer JD, Shyroka O, Kiens B, van Denderen BJ, Tarnopolsky MA, Kemp BE, Richter EA, Steinberg GR. 2011 Sep 20
AMP-activated protein kinase (AMPK) β1 or β2 subunits are required for assembling of AMPK heterotrimers and are important for regulating enzyme activity and cellular localization. In skeletal muscle, α2β2γ3-containing heterotrimers predominate. However, compensatory up-regulation and redundancy of AMPK subunits in whole-body AMPK α2, β2, and γ3 null mice has made it difficult to determine the physiological importance of AMPK in regulating muscle metabolism, because these models have normal mitochondrial content, contraction-stimulated glucose uptake, and insulin sensitivity....

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Bimodal effect on pancreatic β-cells of secretory products from normal or insulin-resistant human skeletal muscle. Bouzakri K, Plomgaard P, Berney T, Donath MY, Pedersen BK, Halban PA. Diabetes. Apr 2011
OBJECTIVE: Type 2 diabetes is characterized by insulin resistance with a relative deficiency in insulin secretion. This study explored the potential communication between insulin-resistant human skeletal muscle and primary (human and rat) β-cells. RESEARCH DESIGN AND METHODS: Human skeletal muscle cells were cultured for up to 24 h with tumor necrosis factor (TNF)-α to induce insulin resistance, and mRNA expression for cytokines was analyzed and compared with controls (without TNF-α). Conditioned media were collected and candidate cytokines were measured by...

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Molecular mechanism by which AMP-activated protein kinase activation promotes glycogen accumulation in muscle. Hunter RW, Treebak JT, Wojtaszewski JF, Sakamoto K. Diabetes. 2011 Mar
During energy stress, AMP-activated protein kinase (AMPK) promotes glucose transport and glycolysis for ATP production, while it is thought to inhibit anabolic glycogen synthesis by suppressing the activity of glycogen synthase (GS) to maintain the energy balance in muscle. Paradoxically, chronic activation of AMPK causes an increase in glycogen accumulation in skeletal and cardiac muscles, which in some cases is associated with cardiac dysfunction. The aim of this study was to elucidate the molecular mechanism by which AMPK activation promotes muscle glycogen accumulation....

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Exercise-induced myokines and their role in chronic diseases.
Pedersen BK. Brain Behav Immun. 2011 Feb 25.
Physical inactivity has recently been identified as a major and independent risk factor for the development of dementia and cognitive decline. In addition to the effect of exercise with regard to protection against neurodegenerative diseases, it is well-established that physical inactivity increases the risk of type 2 diabetes, cardiovascular diseases (CVD), colon cancer and postmenopausal breast cancer. These diseases constitute a network of related diseases, also called "the diseasome of physical inactivity"....

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Impaired insulin-induced site-specific phosphorylation of TBC1 domain family, member 4 (TBC1D4) in skeletal muscle of type 2 diabetes patients is restored by endurance exercise-training. Vind BF, Pehmøller C, Treebak JT, Birk JB, Hey-Mogensen M, Beck-Nielsen H, Zierath JR, Wojtaszewski JF, Højlund K. Diabetologia. 2011 Jan
Insulin-mediated glucose disposal rates (R(d)) are reduced in type 2 diabetic patients, a process in which intrinsic signalling defects are thought to be involved. Phosphorylation of TBC1 domain family, member 4 (TBC1D4) is at present the most distal insulin receptor signalling event linked to glucose transport. In this study, we examined insulin action on site-specific phosphorylation of TBC1D4 and the effect of exercise training on insulin action and signalling to TBC1D4 in skeletal muscle from type 2 diabetic patients....

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Lipid-induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signaling. Høeg LD, Sjøberg KA, Jeppesen J, Jensen TE, Frøsig C, Birk JB, Bisiani B, Hiscock N, Pilegaard H, Wojtaszewski JF, Richter EA, Kiens B. Diabetes. 2011 Jan
We have previously shown that overnight fasted women have higher insulin-stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid-induced insulin resistance....

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Exercise induces a marked increase in plasma follistatin: evidence that follistatin is a contraction-induced hepatokine.
Hansen J, Brandt C, Nielsen AR, Hojman P, Whitham M, Febbraio MA, Pedersen BK, Plomgaard P. Endocrinology. 2011 Jan;152(1):164-71.

Follistatin is a member of the TGF-β super family and inhibits the action of myostatin to regulate skeletal muscle growth. The regulation of follistatin during physical exercise is unclear but may be important because physical activity is a major intervention to prevent age-related sarcopenia. First, healthy subjects performed either bicycle or one-legged knee extensor exercise. Arterial-venous differences were assessed during the one-legged knee extensor experiment....

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Exercise-induced liver CXCL-1 expression is linked to muscle derived IL-6 expression.
Pedersen L, Pilegaard H, Hansen J, Brandt C, Adser H, Hidalgo J, Olesen J, Pedersen BK, Hojman P.J Physiol. 2011 Jan 4.

Background: The chemokine CXC ligand-1 (CXCL-1) is a small cytokine that elicits effects by signalling through the chemokine receptor CXCR2. CXCL-1 has neutrophil chemoattractant activity, is involved in the processes of angiogenesis, inflammation, and wound healing, and may possess neuroprotective effects. The aim of this study was to unravel the mechanisms whereby CXCL-1 is regulated by exercise in mice....

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Exercise-induced TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle. Frøsig C, Pehmøller C, Birk JB, Richter EA, Wojtaszewski JF. J Physiol. 2010 Nov 15;
TBC1D1 is a Rab-GTPase activating protein involved in regulation of GLUT4 translocation in skeletal muscle. We here evaluated exercise-induced regulation of TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle....

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Lipid induced insulin resistance affects women less than men and is not accompanied by inflammation or impaired proximal insulin signalling. Høeg LD, Sjøberg KA, Jeppesen J, Jensen TE, Frøsig C, Birk JB, Bisiani B, Hiscock N, Pilegaard H, Wojtaszewski JF, Richter EA, Kiens B. Diabetes. 2010 Oct 18.
We have previously shown that overnight fasted women have higher insulin stimulated whole body and leg glucose uptake despite a higher intramyocellular triacylglycerol concentration than men. Women also express higher muscle mRNA levels of proteins related to lipid metabolism than men. We therefore hypothesized that women would be less prone to lipid induced insulin resistance....

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Exercise-induced TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle.
Frøsig C, Pehmøller C, Birk JB, Richter EA, Wojtaszewski JF. J Physiol. 2010 Sep 13.

BC1D1 is a Rab-GTPase activating protein involved in regulation of GLUT4 translocation in skeletal muscle. We here evaluated exercise-induced regulation of TBC1D1 Ser237 phosphorylation and 14-3-3 protein binding capacity in human skeletal muscle. In separate experiments healthy men performed all-out cycle exercise lasting either 30 sec, 2 min or 20 min....

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Muscle Specific MicroRNAs are regulated by Endurance Exercise in Human Skeletal Muscle. Nielsen S, Scheele C, Yfanti C, Akerstrom TC, Nielsen AR, Pedersen BK, Laye MJ. J Physiol. 2010 Aug 19.
Muscle specific miRNAs, myomiRs, have been shown to control muscle development in vitro and are differentially expressed at rest in diabetic skeletal muscle. Therefore, we investigated the expression of these myomiRs, including miR-1, miR-133a, miR-133b and miR-206 in muscle biopsies from vastus lateralis of healthy young males (n=10) in relation to a hyperinsulinemic-euglycemic clamp as well as acute endurance exercise before and after 12 weeks of endurance training....

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PGC-1{alpha} Increases PDH Content But Does Not Change Acute PDH Regulation In Mouse Skeletal Muscle. Kiilerich K, Adser H, Jakobsen AH, Pedersen PA, Hardie DG, Wojtaszewski JF, Pilegaard H. Am J Physiol Regul Integr Comp Physiol. 2010 Aug 18.
The aim was to test if the transcriptional coactivator peroxisome proliferator-activated receptor (PPAR)-gamma coactivator (PGC)1alpha regulates the content of pyruvate dehydrogenase (PDH)-E1alpha and influences PDH activity through regulation of PDK4 expression and subsequently PDH phosphorylation. PGC-1alpha whole body knockout (KO), muscle specific PGC-1alpha overexpressing mice (MCK PGC-1alpha) and littermate wild type (WT) mice underwent two interventions known to affect PDH.... 

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PGC-1alpha-mediated adaptations in skeletal muscle. Olesen J, Kiilerich K, Pilegaard H. Pflugers Arch. 2010 Jun;460(1):153-62.
Lifestyle-related diseases are rapidly increasing at least in part due to less physical activity. The health beneficial effects of regular physical activity include metabolic adaptations in skeletal muscle, which are thought to be elicited by cumulative effects of transient gene responses to each single exercise, but how is this regulated? A potential candidate in this is the transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1alpha, which has been identified as a master regulator of mitochondrial biogenesis, but also been shown to regulate proteins involved in angiogenesis and the anti-oxidant defence as well as to affect expression of inflammatory markers....

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A 2-wk reduction of ambulatory activity attenuates peripheral insulin sensitivity.Krogh-Madsen R, Thyfault JP, Broholm C, Mortensen OH, Olsen RH, Mounier R, Plomgaard P, van Hall G, Booth FW, Pedersen BK. J Appl Physiol. 2010 May
US adults take between approximately 2,000 and approximately 12,000 steps per day, a wide range of ambulatory activity that at the low range could increase risk for developing chronic metabolic diseases. Dramatic reductions in physical activity induce insulin resistance; however, it is uncertain if and how low ambulatory activity would influence peripheral insulin sensitivity.... 

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Differential aetiology and impact of phosphoinositide 3-kinase (PI3K) and Akt signalling in skeletal muscle on in vivo insulin action. Friedrichsen M, Poulsen P, Richter EA, Hansen BF, Birk JB, Ribel-Madsen R, Stender-Petersen K, Nilsson E, Beck-Nielsen H, Vaag A, Wojtaszewski JF. Diabetologia. 2010 Sep;53(9):1998-2007. Epub 2010 May 29.
Insulin resistance in skeletal muscle is a key factor in the development of type 2 diabetes and although some studies indicate that this could be partly attributed to reduced content and activity of various proximal and distal insulin signalling molecules, consensus is lacking. We therefore aimed to investigate the regulation of proximal insulin signalling in skeletal muscle and its effect on glucose metabolism in a large non-diabetic population....

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Increased rate of whole body lipolysis before and after 9 days of bed rest in healthy young men born with low birth weight.
Alibegovic AC, Højbjerre L, Sonne MP, van Hall G, Alsted TJ, Kiens B, Stallknecht B, Dela F, Vaag A. Am J Physiol Endocrinol Metab. 2010 Mar;298(3):E555-64.

Individuals born with low birth weight (LBW) are at risk of developing type 2 diabetes mellitus (T2D), which may be precipitated by physical inactivity. Twenty-two LBW subjects and twenty-three controls were studied before and after bed rest by the hyperinsulinemic euglycemic clamp combined with indirect calorimetry and infusion of stable isotope tracers and preceded by an intravenous glucose tolerance test....

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Reviews 

Muscular interleukin-6 and its role as an energy sensor. Pedersen BK. Med Sci Sports Exerc. 2012 Mar;44(3):392-6.
During recent years, accumulating data have shown that muscle cells are able to produce and secrete several hundred myokines. The finding that muscles produce and release myokines provides a conceptual basis for understanding some of the molecular mechanisms underlying organ cross talk, including muscle-liver and muscle-fat cross talk....

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Social Sciences and Humanities 

Original papers 

English obesity policies: To govern and not to govern. Vallgårda S. Health Policy. 2015 Jun. Problem definitions constitute a crucial part of the policy process. In 2008 the Labour Government presented a plan to reduce the obesity prevalence in England. Only three years later the Conservative-Liberal Government introduced a plan on the same topic, which it presented as new and innovative. The aim of this study is to analyse the respective governments' problematisations of obesity and to identify similarities and differences. Despite the different hues of the two governments, the programmes are surprisingly similar.

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The EU pledge for responsible marketing of food and beverages to children: implementation in food companies. Jensen JD, Ronit K. Eur J Clin Nutr. 2015 Apr. Increasing political pressure on the food industry's marketing activities stimulated the formation of the collective EU Pledge for responsible marketing of foods and beverages to children. The objective of the study is to evaluate the commitments made by companies in joining the pledge for the purpose of assessing its effectiveness in regulating signatory companies' marketing activities.

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Eating practices and diet quality: a population study of four Nordic countries. Holm L, Lund TB, Niva M. Eur J Clin Nutr. 2015. Daily practices related to eating are embedded in the social and cultural contexts of everyday life. How are such factors associated with diet quality relative to motivational factors? And, are associations universal or context-specific? We analyze the relationship between diet quality and the following practices: social company while eating, the regularity and duration of eating and the activity of watching TV while eating.

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Backward- and forward-looking responsibility for obesity: policies from WHO, the EU and England. Vallgårda S, Nielsen ME, Hartlev M, Sandøe P. European Journal of Public Health, 2015 Apr. In assigning responsibility for obesity prevention a distinction may be drawn between who is responsible for the rise in obesity prevalence ('backward-looking responsibility'), and who is responsible for reducing it ('forward-looking responsibility').

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The Danish tax on saturated fat: why it did not survive. Vallgårda S, Holm L, Jensen JD. Eur J Clin Nutr. 2015 Feb. 69, 223-226. Health promoters have repeatedly proposed using economic policy tools, taxes and subsidies, as a means of changing consumer behaviour. As the first country in the world, Denmark introduced a tax on saturated fat in 2011. It was repealed in 2012. In this paper, we present arguments and themes involved in the debates surrounding the introduction and the repeal.

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Explaining consumer choice: a critique of the theory of planned behaviour,". Gronow, J. & Holm, L. In The Consumer in Society. A Tribute to Eivind Stø, P. Strandbakken & J. Gronow, eds., Oslo: Abstrakt forlag,2015, pp. 123-148.

Obesity, International Food and Beverage Industries and Self-regulation: The Fragmentation of Information Strategies. Ronit K, Jensen JD. World Medical and Health Policy 2015.

Stigmatisation as a Public Health Tool against Obesity – A Health and Human Rights Perspective. Hartlev M. European Journal of Health Law 21 (2014), pp. 365-386.

Qualitative research building real-life interventions: user-involving development of a mindfulness-based lifestyle change support program for overweight citizens. Hansen NV, Brændgaard P, Hjørnholm C, la Cour S. Eur J Clin Nutr. 2014 Jun. This study is an experiment of putting social sciences to work in developing a support intervention for healthy lifestyle changes that would be attractive and manageable in real-life settings. Starting with a hypothesis that a class of intervention methods based on an unconventional 'low-tension' strategy may offer an effective support of stable, long-term changes well integrated in everyday life, difficult to maintain with conventional dieting and self-control approaches, this study focuses on designing and optimizing an intervention model combining several low-tension methods: mindfulness, small steps and group support.

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Are young people caught in the time bind? A sociological analysis of how young people in an upper secondary school view the issue of finding time to do sports or exercise in their spare time. Friis Thing L, Frydendal Nielsen S & Ottesen L, Annals of Leisure Research 2014. New research shows that even young people, who are still undertaking an education, have difficulties with getting school, work, and family and leisure life to form a synthesis. The article reveals that young people's relationship to sport and physical activity in leisure time is related to the young people's experience of time pressure in the everyday life.

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Obesity and industry self-regulation of food and beverage marketing: a literature review. Ronit K, Jensen JD. Eur J Clin Nutrition April 2014.
Obesity is a growing concern at national and international levels, and it is increasingly recognised that the industry has a role in and hence needs to be involved in halting the obesity epidemic. The objective of this study is to describe, analyse and evaluate research on industry self-regulation regarding food and beverage marketing and nutrition labelling...

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Young people's perspectives on health, risks and physical activity in a Danish secondary school. Friis Thing L & Ottesen L. Health, Risk & Society, 2013. In this article, we examine how risk discourses related to health and physical activity are used and understood by the young people in a Danish school setting. We aim to give a detailed account of students’ experiences and to present their views on how they understand and comprehend matters concerning their own health.

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Should we Hold the Obese Responsible? Some Key Issues. Nielsen MEJ and Andersen MM. Cambridge Quarterly of Healthcare Ethics 2013. It is a common belief that obesity is wholly or partially a question of personal choice and personal responsibility. It is also widely assumed that when individuals are responsible for some unfortunate state of affairs, society bears no burden to compensate them. This article focuses on two conceptualizations of responsibility: backward-looking and forward-looking conceptualizations.

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Bioethics in Denmark. Nielsen MEJ and Andersen MM. Cambridge Quarterly of Healthcare Ethics 2013. This article examines two current debates in Denmark--assisted suicide and the prioritization of health resources--and proposes that such controversial bioethical issues call for distinct philosophical analyses: first-order examinations, or an applied philosophy approach, and second-order examinations, what might be called a political philosophical approach.

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Obesity as a showcase for transdisciplinary research. Holm L, Børker Nielsen P, Sandøe P, Juul Nielsen ME. Obes Facts. 2013.
Obesity is one of the main health problems in the world with high societal and individual costs. To tackle the obesity epidemic, we need to collaborate across scientific boarders to fundamentally broaden the perspectives on the obesity epidemic as a complex phenomenon...

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Is it acceptable to use animals to model obese humans? – A critical discussion of two arguments against the use of animals in obesity research. Lund TB, Sørensen TI, Olsson IA, Hansen AK and Sandøe P.J Med Ethics, 2013. Animal use in medical research is widely accepted on the basis that it may help to save human lives and improve their quality of life. Recently, however, objections have been made specifically to the use of animals in scientific investigation of human obesity. This paper discusses two arguments for the view that this form of animal use, unlike some other forms of animal-based medical research, cannot be defended...

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The Danish tax on saturated fat – Short run effects on consumption, substitution patterns and consumer prices of fats. Jørgen Dejgård Jensen & Sinne Smed. Food Policy, Volume 42, October 2013

Denmark introduced a tax on saturated fat in food products with effect from October 2011. The objective of this paper is to make an effect assessment of this tax for some of the product categories most significantly affected by the new tax, namely fats such as butter, butter-blends, margarine and oils. 

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Food Industry Firms' Economic Incentives to Provide Nutritional Information to the Market: European Breakfast Cereals, Snacks, and Soft Drinks Industries, Jensen JD & Ronit K. Journal of International Food & Agribusiness Marketing, 2013

Information asymmetries between producers and consumers exist with respect to nutritional characteristics of foods and beverages. This article aims to analyze firms' methods to supply nutritional information, focusing on 3 specific food industries: breakfast cereals, snacks, and soft drinks. A theoretical model is developed and tested empirically on European firm-level data obtained from company websites.

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Should we Equalize Status in order to Equalize Health? - Morten Ebbe Juul Nielsen (Martin Marchman, Xavier Landes). Journal of Public Health Ethics, 2013

If it is true, as suggested by Sir Michael Marmot and other researchers, that status impacts health and therefore accounts for some of the social gradient in health, then it seems to be the case that it would be possible to bring about more equality in health by equalizing status. The purpose of this article is to analyze this suggestion. First, we suggest a working definition of what status precisely is. Second, following a luck egalitarian approach to distributive justice, we consider whether and to which extent individuals are responsible themselves for their position in a status hierarchy. Third, we consider...

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Healthy Ageing — A Patients' Rights Perspective. Hartlev, Mette. European Journal of Health Law, Volume 19, Number 2, 2012 , pp. 141-155(15).
The demographic development is a challenge for the European healthcare systems, and to meet these challenges it is crucial to develop efficient health preventive strategies to ensure that the population is, and stays fit as long as possible. However, along with demographic development, Europe is also facing a boom in lifestyle diseases which constitute an impediment for healthy ageing....

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Obesity in Europe: The Strategy of the European Union from a Public Health Law Perspective. Faeh, Andrea. European Journal of Health Law, Volume 19, Number 1, 2012 , pp. 69-86(18).
In 2007 the European Commission published a White Paper on a “Strategy on nutrition, overweight and obesity“, proposing measures to impede the current trend towards a steady gain in weight by Union citizens. In this article, these ideas are discussed critically in the light of the competences of the Union and from a public health law perspective, in order to scrutinise the effectiveness of the measures and to identify shortcomings in the White Paper....

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Nudge-A new and better way to improve health? Vallgårda S. Health Policy , vol 104, nr. 2, s. 200-203, 2012
Nudging, or libertarian paternalism, is presented as a new and ethically justified way of improving people's health. It has proved influential and is currently taken up by the governments in the US, the UK and France. One may question the claim that the approach is new, in any case it has many similarities with the idea of "making healthy choices easier". Whether the approach is better from an ethical perspective depends on the ethical principles one holds. From a paternalistic perspective there could be no objections, but from a libertarian, there are several. Contrary to what the authors state, libertarian paternalism is an oxymoron.

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Sundhed - et frit valg? Anne Sundby, Mette Hartlev. I "Frit valg. Velfærd i Den Europæiske Union". Sune Troels Poulsen & Stine Jørgensen (red.). Jurist- og Økonomforbundets Forlag. 2011.

 

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The ethnics of prevention. Vallgårda S. Bibl Læger 2011;203:252-74.
In this article ethical dilemmas in public health are discussed, and three approaches to public health ethics are described. The moral theories in focus are liberalism, paternalism and community-orientated theories; the latter divided into a republican and a socialistic variant. The understanding of humans and society and the underlying ethical principles of the three approaches are discussed, as is the criticism raised by other approaches. The presentation is mainly based on scholarly literature from the USA, where public health ethics have been discussed and analysed much more in depth than in Europe. It is concluded that none of the principles are (or should be) consistently followed in public health policy, and that the present Danish health policy is based on a combination of all three positions....

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Unges syn på idræt, bevægelse og sundhed i gymnasieskolen. En kvantitativ undersøgelse af Rysensteen Gymnasium. Stine Frydendal Nielsen, Marianne Brandt-Hansen, Glen Nielsen, Laila Ottesen, Lone Friis Thing. 2011.

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Why the concept ‘‘lifestyle diseases'' should be avoided. Vallgårda S. Scand J Public Health Sep 2011 39: 773-775.
The concept lifestyle disease is used about a number of different diseases such as coronary heart disease, diabetes, lung cancer etc. The concept indicates that people's behaviours cause the diseases. This is only partly true. All diseases, both so-called lifestyle diseases and infectious diseases, have multiple causes.

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Åbne Fodboldbaner i Dagtimerne. Igangsættelse af Motionstiltag for Inaktive Grupper: Hvidbog om sundhedsfremme i kommunalt regi, Krustrup, BR , Nielsen, SF & Ottesen, L 2011.

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Attitudes to Publicly Funded Obesity Treatment and Prevention.
Lund TB, Sandøe P, Lassen J. SourceDepartment of Human Nutrition, Faculty of Life Sciences, University of Copenhagen, Frederiksberg, Denmark.

The aim of this study was to investigate the Danish public's support for publicly funded obesity treatment and prevention. It was also examined whether levels of support could be explained by dislike of obese people and/or the belief that those who are obese are personally responsible for their condition....

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Addressing individual behaviours and living conditions: Four Nordic public health policies. Vallgårda S. Scandinavian Journal of Public Health. 2011;39 (6 suppl.):6-10. 
Aims: To identify characteristics of the public health policies of four Nordic countries concerning how they present the causes of ill health, the best ways to deal with these causes, and where to place responsibility; additionally, to investigate whether there is a common Nordic policy. Methods: Analyses of recent public health programmes in Denmark, Finland, Norway, and Sweden....

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Appeals to autonomy and obedience. Continuity and change in governing technologies in health promotion. Vallgårda S. Medical History. 2011;55/1:27-40.
The increasingly used concept new public health indicates that a fundamental change has occurred in the goals and methods of disease prevention and health promotion. The change is often said to imply less expert-driven governing of citizens. In this article, governing technologies in the field of public health in Denmark and Sweden are analysed to investigate whether substantial changes have taken place in the governing efforts....

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Republicanism as a Paradigm for Public Health - Some Comments
Morten Ebbe Juul Nielsen Public Health Ethics 2011; doi: 10.1093/phe/phr003

Some theorists, worried about liberalism's potential as a foundation for public health ethics, suggest that republicanism provides a better background of justification for public health policies, interventions, etc. In this article, this suggestion is put to the test, and it is argued that (i) contemporary (civic) republicanism and liberalism are not nearly as opposed as it is sometimes suggested, and that (ii) the kind of republicanism which one leading scholar in the field, Bruce Jennings, as an alternative to liberalism, does not reflect the contemporary understanding of republicanism as held by, e.g. Phillip Pettit et al....

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Prioritering og social retfærdighed. I Størup et al (red): Det sunde valg. Sundhedsstyrelsen. Morten EJ Nielsen(2010)

 

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Is the focus on health-related behaviours a new phenomenon? Vallgårda S. Social Studies of Science. 2010:40(4):609-14.
In his article ‘Origins of the Problem of Health-related Behaviours: A Genealogical Study', David Armstrong claims that the idea about ‘changeable behaviour is a relatively recent phenomenon'. In this paper it is argued that this conclusion is not valid....

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Ida spielt ihr eigenes Spiel - "doing gender" im Sportunterricht ', Pfister, Gertrud & With-Nielsen, Ninna (2010), Spectrum der Sportwissenschaften , vol 22, nr. 2, s. 43-63.  

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Social class and body management. A qualitative exploration of differences in perceptions and practices related to health and personal body weight. Smith LH, Holm L. Appetite. Oct. 2010;55:311-8.
To deepen our understanding of the relationship between social class and obesity, the study compares the ways in which conceptions of health and personal body weight are enmeshed in the everyday lives of people with disparate socio-cultural backgrounds and weight status. We ask how perceptions and enactments of health and personal body weight are related to social structures and practices at work, in spare time, and in family life....

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The development of social capital through soccer and running: The experience of a 16 weeks intervention programme for inactive, inexperienced women. Laila Ottesen, R. Jeppesen, B. Krustrup. Scandinavian Journal of Medicine & Science in Sports. Vol.20. supplement 1, april 2010, p.118-131.
This article examines the development of social capital through the use and dynamics of different types of stories ("I,""we" and "they") as described by Robert D. Putnam. The data come from a research project in which inactive women participated in a 16-week intervention program of physical exercise, either in the form of football or running. The study shows a positive development of social capital in the two different types of physical activity. The I-stories show themselves to be central to bonding within the two groups and bridging outside the groups (developing and/or creating networks). The study also points to the importance of the activity itself for internal bonding illustrated through we- and they-stories. Our data indicate that team sports, such as football, may have an advantage over individual sports in the development of social capital....

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Til toppenGenetic-Epidemiology theme

Original papers 

Gender and obesity specific microRNA expression in adipose tissue from lean and obese pigs. Mentzel CMJ, Anthon C, Jacobsen MJ, Karlskov-Mortensen P, Bruun CS, Jørgensen CB , Gorodkin J, Cirera S and Fredholm M. 2015. In press.

Stable intergenerational associations of childhood overweight during the development of the obesity epidemic. Ajslev TA, Ängquist L, Silventoinen K, Baker JL, Sørensen TI. Obesity (Silver Spring). 2015. This investigation examined whether the intergenerational resemblances in childhood overweight changed across the development of the obesity epidemic in groups of children born to parents with and without childhood overweight. Parent-child resemblance in childhood overweight showed small changes during the development of the obesity epidemic, suggesting that the obesogenic environment inducing the epidemic in Denmark influenced children irrespective of their familial predisposition.

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Comparative Analyses of QTLs influencing Obesity and Metabolic Phenotypes in Pigs and Humans. Pant SD, Karlskov-Mortensen P, Jacobsen MJ, Cirera S, Kogelman LJA, Bruun CS, Mark T, Jørgensen CB, Grarup N, Appel EVR, Galjatovic EAA, Hansen T, Pedersen O, Guerin M, Huby T, Lesnik P, Meuwissen THE, Kadarmideen HN and Fredholm M. Submitted to Plos One.

Altered methylation profile of lymphocytes is concordant with perturbation of the inflammatory response in obesity. Jacobsen MJ, Mentzel CMJ, Olesen AS, Huby T, Jørgensen CB, Barres R, Fredholm M and Simar D. Journal of Diabetes Research. Ankarfeldt MZ, Larsen SC, Ängquist L, Husemoen LL, Roswall N, Overvad K, Jakobsen MU, Halkjær J, Tjønneland A, Linneberg A, Toft U, Hansen T, Pedersen O, Heitmann BL, Astrup A, Sørensen TI. PLoS One. 2014. BACKGROUND: Genetic predisposition to adiposity may interact with dietary protein in relation to changes of anthropometry.OBJECTIVE: To investigate the interaction between genetic predisposition to higher body mass index (BMI), waist circumference (WC) or waist-hip ratio adjusted for BMI (WHRBMI) and dietary protein in relation to subsequent change in body weight (ΔBW) or change in WC (ΔWC). CONCLUSION: This study indicates that the genetic predisposition to general and abdominal adiposity, assessed by gene-scores, does not seem to modulate the influence of dietary protein on ΔBW or ΔWC.

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Interaction between genetic predisposition to obesity and dietary calcium in relation to subsequent change in body weight and waist circumference. Larsen SC, Ängquist L, Ahluwalia TS, Skaaby T, Roswall N, Tjønneland A, Halkjær J, Overvad K, Pedersen O, Hansen T, Linneberg A, Husemoen LL, Toft U, Heitmann BL, Sørensen TI. Am J Clin Nutr. 2014. The objective was to examine whether genetic predisposition to higher body mass index (BMI), WC, or waist-hip ratio (WHR) interacts with dietary calcium in relation to subsequent annual change in BW (ΔBW) and WC (ΔWC). Our study suggests that dietary calcium relates weakly to BW loss. We found no evidence of a general association between calcium and ΔWC, but calcium may reduce WC among people genetically predisposed to a high WC. However, further replication of this finding is needed.

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Interaction between genetic predisposition to adiposity and dietary protein in relation to subsequent change in body weight and waist circumference.

Systems genetics analysis of obesity using RNA-Seq data in an F2 pig ressource population. Kogelman L, Zhernakova DV, Westra H-J, Cirera S, Fredholm M, Franke L, Kadarmideen HN. Proceeding 10th World Congress, 2014. Obesity is a complex problem, Associated with many diseases. Microarray gene expression data have been extensively used to detect differentially expressed (DE) genes and expression quantitative trait loci (eQTL, however, RNA-Sequencing data have the potential to reveal novel genes involved in complex traits. The objective was to elucidate biological pathways and potential biomarkers for obesity in a porcine model, by systems genetics approaches using RNA-Sequencing data.

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Systems genetics of obesity in an F2 pig model by genome-wide association, genetic network and pathway analyses. Lisette Kogelman ; Sameer Dinkar Pant ; Merete Fredholm ; Haja Kadarmideen. Frontiers in Genetics, section Systems Biology, Vol. 5, 07.2014, s. 214. Here, the aim was to perform an integrative genomic analysis in an F2 pig resource population that was constructed with an aim to maximize genetic variation of obesity-related phenotypes and genotyped using the 60K SNP chip.

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Trends in parent-child correlations of childhood body mass index during the development of the obesity epidemic. Ajslev TA, Ängquist L, Silventoinen K, Baker JL, Sørensen TI. PLoS One. 2014. This study investigates trends in intergenerational correlations of childhood body mass index (BMI; kg/m2) during the emergence of the obesity epidemic. During the obesity epidemics development, the intergenerational resemblance with mothers remained stable, whereas the father-child BMI resemblance increased, possibly reflecting changes in family relationships, and unlikely to have influenced the epidemic.

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Association between Mediterranean and Nordic diet scores and changes in weight and waist circumference: influence of FTO and TCF7L2 loci. Roswall N, Angquist L, Ahluwalia TS, Romaguera D, Larsen SC, Ostergaard JN, Halkjaer J, Vimaleswaran KS, Wareham NJ, Bendinelli B, Palli D, Boer JM, van der AD, Boeing H, Loos RJ, Sørensen TI, Tjonneland A. Am J Clin Nutr 2014. Several studies have shown that adherence to the Mediterranean Diet measured by using the Mediterranean diet score (MDS) is associated with lower obesity risk. The newly proposed Nordic Diet could hold similar beneficial effects. Because of the increasing focus on the interaction between diet and genetic predisposition to adiposity, studies should consider both diet and genetics

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Interactions of dietary protein and adiposity measures in relation to subsequent changes in body weight and waist circumference. Ankarfeldt MZ, Angquist L, Jakobsen MU, Overvad K, Tjonneland A, Halkjaer J, Astrup A, Sørensen TI. Obesity (Silver Spring) 2014. To investigate if dietary protein and degree of adiposity interacts in relation to change in body weight and waist circumference (WC) in the general population.

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Dietary protein and urinary nitrogen in relation to 6-year changes in fat mass and fat-free mass. Ankarfeldt MZ, Gottliebsen K, Angquist L, Astrup A, Heitmann BL, Sørensen TI. Int J Obes (Lond) 2014. Background:In contrast to the physiological expectation, observational studies show that greater protein intake is associated with subsequent body weight (BW) gain. An increase in fat-free mass (FFM) due to the anabolic effects of protein could explain this.Objective:To examine associations between protein intake and subsequent changes in fat mass (FM) and FFM in longitudinal, observational data.

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Body composition, dietary protein and body weight regulation. Reconciling conflicting results from intervention and observational studies? Ankarfeldt MZ, Angquist L, Stocks T, Jakobsen MU, Overvad K, Halkjaer J, Saris WH, Astrup A, Sørensen TI.  PLoS One 2014, 9: e101134. Physiological evidence indicates that high-protein diets reduce caloric intake and increase thermogenic response, which may prevent weight gain and regain after weight loss. Clinical trials have shown such effects, whereas observational cohort studies suggest an association between greater protein intake and weight gain. In both types of studies the results are based on average weight changes, and show considerable diversity in both directions. This study investigates whether the discrepancy in the evidence could be due to recruitment of overweight and obese individuals into clinical trials.

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Consumption of pre-defined 'Nordic' dietary items in 10 European countries - an investigation in the EPIC Cohort. Roswall N, Olsen A, Boll K, Christensen J, Halkjær J, Sørensen TIA et al. Public Health Nutr. 2014 Mar 3:1-10. The present study describes the intake of seven a priori defined healthy food items (apples/pears, berries, cabbages, dark bread, shellfish, fish and root vegetables) across ten countries participating in the European Prospective Investigation into Cancer and Nutrition (EPIC) and examines their consumption across Europe.

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Risk of Childhood Overweight after Exposure to Tobacco Smoking in Prenatal and Early Postnatal Life. Møller SE, Ajslev TA, Andersen CS, Dalgård C, Sørensen TI. 2014. To investigate the association between exposure to mothers smoking during prenatal and early postnatal life and risk of overweight at age 7 years, while taking birth weight into account. Mother's perinatal smoking increased child's OR of overweight at age 7 years irrespective of birth weight, and with higher OR if exposed both during pregnancy and in early postnatal life. Clear dose-response relationships were observed, which emphasizes the need for prevention of any tobacco exposure of infants.

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Variation in genes related to hepatic lipid metabolism and changes in waist circumference and body weight. Meidtner K, Fisher E, Angquist L, Holst C, Vimaleswaran KS, Boer JM, Halkjær J, Masala G, Ostergaard JN, Mortensen LM, van der A DL, Tjønneland A, Palli D, Overvad K, Wareham NJ, Loos RJ, Sørensen TI, Boeing H. Genes Nutr. 2014 Mar;9(2):385. We analysed single nucleotide polymorphisms (SNPs) tagging the genetic variability of six candidate genes (ATF6, FABP1, LPIN2, LPIN3, MLXIPL and MTTP) involved in the regulation of hepatic lipid metabolism, an important regulatory site of energy balance for associations with body mass index (BMI) and changes in weight and waist circumference. We also investigated effect modification by sex and dietary intake.

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Compass: a hybrid method for clinical and biobank data mining. Krysiak-Baltyn K, Pedersen TN, Audouze K, Jørgensen N, *Ängquist L, Brunak S.  Journal of Biomedical Informatics; 2014 Feb;47:160-70. We describe a new method for identification of confident associations within large clinical data sets. The method is a hybrid of two existing methods; Self-Organizing Maps and Association Mining. We utilize Self-Organizing Maps as the initial step to reduce the search space, and then apply Association Mining in order to find association rules.

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Dietary ascorbic acid and subsequent change in body weight and waist circumference: associations may depend on genetic predisposition to obesity - a prospective study of three independent cohorts. Larsen SC, Ängquist L, Ahluwalia TS, Skaaby T, Roswall N, Tjønneland A, Halkjær J, Overvad K, Pedersen O, Hansen T, Linneberg A, Husemoen LL, Toft U, Heitmann BL and Sørensen TIA.  Nutrition Journal 2014, 13:43. Cross-sectional data suggests that a low level of plasma ascorbic acid positively associates with both Body Mass Index (BMI) and Waist Circumference (WC). This leads to questions about a possible relationship between dietary intake of ascorbic acid and subsequent changes in anthropometry, and whether such associations may depend on genetic predisposition to obesity.

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Change in proportional protein intake in a 10-weeks energy-restricted low- or high-fat diet, in relation to changes in body size and metabolic factors. Stocks T, Taylor MA, Ängquist L, MacDonald I.A, Arner P, Holst C, Oppert J-M, Martinez JA, Rössner S, Polak J, Langin D, Saris W.H.M, Astrup A, Sørensen T.I.A.  Obesity Facts 2013; 6(3):217-27. To investigate in a secondary analysis of a randomised trial the effects of a low-/high-fat diet and reported change from baseline in energy% from protein (prot%), in relation to changes in body size and metabolic factors.

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24h urinary sodium excretion and subsequent change in weight, waist circumference and body composition. Larsen SC, Ängquist L, Sørensen TIA, Heitmann BL. PLoS ONE 2013: 8(7): e69689. BACKGROUND: In the same period as the increasing obesity epidemic, there has been an increased consumption of highly processed foods with a high salt content, and a few studies have suggested that a diet with a high salt content may be associated with obesity. OBJECTIVE: To investigate the association between 24 h urinary sodium excretion and subsequent change in body weight (BW), waist circumference (WC), body fat (BF) and fat free mass (FFM) among adults.

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Pleiotropic genes for metabolic syndrome and inflammation. Kraja AT, Chasman DI, North KE, Reiner AP, Yanek LR, Kilpeläinen TO, Smith JA, Dehghan A, Dupuis J, Johnson AD, Feitosa MF, Tekola-Ayele F, Chu AY, Nolte IM, Dastani Z, Morris A, Pendergrass SA, Sun YV, Ritchie MD, Vaez A, Lin H, Ligthart S, Marullo L, Rohde R, Shao Y, Ziegler MA, Im HK, Cross Consortia Pleiotropy (XC-Pleiotropy) Group, the Cohorts for Heart and Aging Research in Genetic Epidemiology (CHARGE), the Genetic Investigation of Anthropometric Traits (GIANT) Consortium, the Global Lipids Genetics Consortium (GLGC), the Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), the Global BPgen (GBPG) Consortium, The ADIPOGen Consortium, the Women’s Genome Health Study (WGHS), the Howard University Family Study (HUFS), Schnabel RB, Jørgensen T, Jørgensen ME, Hansen T, Pedersen O, Stolk RP, Snieder H, Hofman A, Uitterlinden AG, Franco OH, Ikram MA, Richards JB, Rotimi C, Wilson JG, Lange L, Ganesh SK, Nalls M, Rasmussen-Torbik LJ, Pankow JS, Coresh J, Tang W, Kao WHL, Boerwinkle E, Morrison AC, Ridker PM, Becker DM, Rotter JI, Kardia SLR, Loos RJF, Larson MG, Hsu YH, Province MA, Tracy R, Voight BF, Vaidya D, O’Donnell C, Benjamin EJ, Alizadeh BZ, Prokopenko I, Meigs JB, Borecki IB. Mol Genet Metab Aug 2014. Our study hypothesis is that additional to genes influencing individual MetS risk factors, genetic variants exist that influence MetS and inflammatory markers forming a predisposing MetS genetic network.

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Whole-exome sequencing of 2,000 Danish individuals and the role of rare coding variants in type 2 diabetes. Lohmueller KE, Sparsø T, Li Q, Andersson E, Korneliussen T, Albrechtsen A, Banasik K, Grarup N, Hallgrimsdottir I, Kiil K, Kilpeläinen TO, Krarup NT, Pers TH, Sanchez G, Hu Y, Degiorgio M, Jørgensen T, Sandbæk A, Lauritzen T, Brunak S, Kristiansen K, Li Y, Hansen T, Wang J, Nielsen R, Pedersen O. Am J Hum Genet 2013;93:1072-86.  It has been hypothesized that, in aggregate, rare variants in coding regions of genes explain a substantial fraction of the heritability of common diseases. We sequenced the exomes of 1,000 Danish cases with common forms of type 2 diabetes (including body mass index > 27.5 kg/m(2) and hypertension) and 1,000 healthy controls to an average depth of 56×.

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Expression studies of six human obesity-related genes in seven tissues from divergent pig breeds. Cirera S, Jensen MS, Elbrønd VS, Moesgaard SG, Christoffersen BO, Kadarmideen HN, Skovgaard K, Bruun CV, Karlskov-Mortensen P, Jørgensen CB, Fredholm M. Anim Genet. 2013 Aug.
Obesity has reached epidemic proportions globally and has become the cause of several major health risks worldwide. Presently, more than 100 loci have been related to obesity and metabolic traits in humans by genome-wide association studies...

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Genetic architecture of vitamin B12 and folate levels uncovered applying deeply sequenced large datasets. Grarup N, Sulem P, Sandholt CH, Thorleifsson G, Ahluwalia TS, Steinthorsdottir V, Bjarnason H, Gudbjartsson DF, Magnusson OT, Sparsø T, Albrechtsen A, Kong A, Masson G, Tian G, Cao H, Nie C, Kristiansen K, Husemoen LL, Thuesen B, Li Y, Nielsen R, Linneberg A, Olafsson I, Eyjolfsson GI, Jørgensen T, Wang J, Hansen T, Thorsteinsdottir U, Stefánsson K, Pedersen O. PLoS Genet. 2013 Jun.
Genome-wide association studies have mainly relied on common HapMap sequence variations. Recently, sequencing approaches have allowed analysis of low frequency and rare variants in conjunction with common variants, thereby improving the search for functional variants and thus the understanding of the underlying biology of human traits and diseases...

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Exome sequencing-driven discovery of coding polymorphisms associated with common metabolic phenotypes. Albrechtsen A, Grarup N, Li Y, Sparsø T, Tian G, Cao H, Jiang T, Kim SY, Korneliussen T, Li Q, Nie C, Wu R, Skotte L, Morris AP, Ladenvall C, Cauchi S, Stančáková A, Andersen G, Astrup A, Banasik K, Bennett AJ, Bolund L, Charpentier G, Chen Y, Dekker JM, Doney AS, Dorkhan M, Forsen T, Frayling TM, Groves CJ, Gui Y, Hallmans G, Hattersley AT, He K, Hitman GA, Holmkvist J, Huang S, Jiang H, Jin X, Justesen JM, Kristiansen K, Kuusisto J, Lajer M, Lantieri O, Li W, Liang H, Liao Q, Liu X, Ma T, Ma X, Manijak MP, Marre M, Mokrosiński J, Morris AD, Mu B, Nielsen AA, Nijpels G, Nilsson P, Palmer CN, Rayner NW, Renström F, Ribel-Madsen R, Robertson N, Rolandsson O, Rossing P, Schwartz TW; D.E.S.I.R. Study Group, Slagboom PE, Sterner M; DIAGRAM Consortium, Tang M, Tarnow L, Tuomi T, van't Riet E, van Leeuwen N, Varga TV, Vestmar MA, Walker M, Wang B, Wang Y, Wu H, Xi F, Yengo L, Yu C, Zhang X, Zhang J, Zhang Q, Zhang W, Zheng H, Zhou Y, Altshuler D, 't Hart LM, Franks PW, Balkau B, Froguel P, McCarthy MI, Laakso M, Groop L, Christensen C, Brandslund I, Lauritzen T, Witte DR, Linneberg A, Jørgensen T, Hansen T, Wang J, Nielsen R, Pedersen O. Diabetologia. 2013 Feb.
Human complex metabolic traits are in part regulated by genetic determinants. Here we applied exome sequencing to identify novel associations of coding polymorphisms at minor allele frequencies (MAFs) >1% with common metabolic phenotypes...

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An f2 pig resource population as a model for genetic studies of obesity and obesity-related diseases in humans: design and genetic parameters. Kogelman LJ, Kadarmideen HN, Mark T, Karlskov-Mortensen P, Bruun CS, Cirera S, Jacobsen MJ, Jørgensen CB, Fredholm M. Front Genet, 2013

Obesity is a rising worldwide public health problem. Difficulties to precisely measure various obesity traits and the genetic heterogeneity in human have been major impediments to completely disentangle genetic factors causing obesity. The pig is a relevant model for studying human obesity and obesity-related (OOR) traits.

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Being an only or last-born child increases later risk of obesity. Haugaard LK, Ajslev TA, Zimmermann E, Angquist L, Sørensen TI. PLoS One, Epub Feb 2013
BACKGROUND: Studies have suggested that number of siblings and birth order is associated with obesity. However, studies combining these exposures are needed. This study aimed at investigating obesity in children and young adults in regard to different combinations of family size and birth order. METHODS: TWO COHORTS SELECTED FROM THE GENERAL POPULATION WERE INVESTIGATED: The Copenhagen School Health Records Register (CSHRR) and a Draft Board (DB) sample...

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TFAP2B -Dietary Protein and Glycemic Index Interactions and Weight Maintenance after Weight Loss in the DiOGenes Trial. Stocks T, Angquist L, Hager J, Charon C, Holst C, Martinez JA, Saris WH, Astrup A, Sørensen TI, Larsen LH. Hum Hered. 2013.
TFAP2B rs987237 is associated with obesity and has shown interaction with the dietary fat-to-carbohydrate ratio, which has an effect on weight loss. We investigated interactions between rs987237 and protein-to-carbohydrate ratio or glycemic index (GI) in relation to weight maintenance after weight loss...

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TFAP2B influences the effect of dietary fat on weight loss under energy restriction. Stocks T, Angquist L, Banasik K, Harder MN, Taylor MA, Hager J, Arner P, Oppert JM, Martinez JA, Polak J, Rousseau F, Langin D, Rössner S, Holst C, MacDonald IA, Kamatani Y, Pfeiffer AF, Kunesova M, Saris WH, Hansen T, Pedersen O, Astrup A, Sørensen TI. PLoS One, 2012
BACKGROUND: Numerous gene loci are related to single measures of body weight and shape. We investigated if 55 SNPs previously associated with BMI or waist measures, modify the effects of fat intake on weight loss and waist reduction under energy restriction. METHODS AND FINDINGS: Randomized controlled trial of 771 obese adults. (Registration: ISRCTN25867281.) One SNP was selected for...

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Modifiable environmental influences on body mass index shared by young adult brothers. Rokholm B, Silventoinen K, Tynelius P, Sørensen TI, Rasmussen F. Int J Obes (Lond). 2012 Sep.
OBJECTIVES:Twin and adoption studies suggest that family environment has little, if any, influence on body mass index (BMI) in adulthood. We investigated the hypothesis that the differences in the years of birth between siblings influence their similarity in BMI at comparable ages, which would give evidence for a possibly modifiable influence of the environment shared by family members....

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Assortative marriages by body mass index have increased simultaneously with the obesity epidemic. Ajslev TA, Angquist L, Silventoinen K, Gamborg M, Allison DB, Baker JL, Sørensen TI. Front Genet. 2012 Jul.
Background: The genetic predisposition to obesity may have contributed to the obesity epidemic through assortative mating. We investigated whether spouses were positively assorted by body mass index (BMI; = kg/m(2)) in late childhood, and whether changes in assorted marriage by upper BMI-percentiles occurred during the obesity epidemic....

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Dietary factors impact on the association between CTSS variants and obesity related traits. Hooton H, Angquist L, Holst C, Hager J, Rousseau F, Hansen RD, Tjønneland A, Roswall N, van der A DL, Overvad K, Jakobsen MU, Boeing H, Meidtner K, Palli D, Masala G, Bouatia-Naji N, Saris WH, Feskens EJ, Wareham NJ, Vimaleswaran KS, Langin D, Loos RJ, Sørensen TI, Clément K. PLoS One. 2012 Jul
Cathepsin S, a protein coded by the CTSS gene, is implicated in adipose tissue biology--this protein enhances adipose tissue development. Our hypothesis is that common variants in CTSS play a role in body weight regulation and in the development of obesity and that these effects are influenced by dietary factors--increased by high protein, glycemic index and energy diets....

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Haploinsufficiency of CELF4 at 18q12.2 is associated with developmental and behavioral disorders, seizures, eye manifestations, and obesity. Halgren C, Bache I, Bak M, Myatt MW, Anderson CM, Brøndum-Nielsen K, Tommerup N. Eur J Hum Genet. 2012 May 23
Only 20 patients with deletions of 18q12.2 have been reported in the literature and the associated phenotype includes borderline intellectual disability, behavioral problems, seizures, obesity, and eye manifestations. Here, we report a male patient with a de novo translocation involving chromosomes 12 and 18, with borderline IQ, developmental and behavioral disorders, myopia, obesity, and febrile seizures in childhood....

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Analyses of single nucleotide polymorphisms in selected nutrient-sensitive genes in weight-regain prevention: the DIOGENES study.Larsen LH, Angquist L, Vimaleswaran KS, Hager J, Viguerie N, Loos RJ, Handjieva-Darlenska T, Jebb SA, Kunesova M, Larsen TM, Martinez JA, Papadaki A, Pfeiffer AF, van Baak MA, Sørensen TIa, Holst C, Langin D, Astrup A, Saris WH. Am J Clin Nutr. 2012 May.
BACKGROUND: Differences in the interindividual response to dietary intervention could be modified by genetic variation in nutrient-sensitive genes. OBJECTIVE: This study examined single nucleotide polymorphisms (SNPs) in presumed nutrient-sensitive candidate genes for obesity and obesity-related diseases for main and dietary interaction effects on weight, waist circumference, and fat mass regain over 6 mo....

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Food composition of the diet in relation to changes in waist circumference adjusted for body mass index. Romaguera D, Ängquist L, Du H, Jakobsen MU, Forouhi NG, Halkjær J, Feskens EJ, van der A DL, Masala G, Steffen A, Palli D, Wareham NJ, Overvad K, Tjønneland A, Boeing H, Riboli E, Sørensen TI. PLoS One. 2011 Aug.
Dietary factors such as low energy density and low glycemic index were associated with a lower gain in abdominal adiposity. A better understanding of which food groups/items contribute to these associations is necessary....

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Increasing Genetic Variance of Body Mass Index during the Swedish Obesity Epidemic. Benjamin Rokholm, Karri Silventoinen, Per Tynelius, Michael Gamborg, Thorkild I. A. Sørensen, Finn Rasmussen. PLoS One. 2011
There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin and family studies suggest that genetic differences are responsible for the major part of the variation in adiposity within populations. Recent studies show that the genetic effects on body mass index (BMI) may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that the genetic variance of BMI has increased during the obesity epidemic....

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Increased genetic variance of BMI with a higher prevalence of obesity. Rokholm B, Silventoinen K, Ängquist L, Skytthe A, Kyvik KO, Sørensen TI. PLoS One. 2011 Jun.
There is no doubt that the dramatic worldwide increase in obesity prevalence is due to changes in environmental factors. However, twin studies suggest that genetic differences are responsible for the major part of the variation in body mass index (BMI) and other measures of body fatness within populations. Several recent studies suggest that the genetic effects on adiposity may be stronger when combined with presumed risk factors for obesity. We tested the hypothesis that a higher prevalence of obesity and overweight and a higher BMI mean is associated with a larger genetic variation in BMI....

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Genetic polymorphisms in the hypothalamic pathway in relation to subsequent weight change--the DiOGenes study. Du H, Vimaleswaran KS, Angquist L, Hansen RD, van der A DL, Holst C, Tjønneland A, Overvad K, Jakobsen MU, Boeing H, Meidtner K, Palli D, Masala G, Bouatia-Naji N, Saris WH, Feskens EJ, Wareham NJ, Sørensen TI, Loos RJ. PLoS One. 2011 Feb
Single nucleotide polymorphisms (SNPs) in genes encoding the components involved in the hypothalamic pathway may influence weight gain and dietary factors may modify their effects....

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The levelling off of the obesity epidemic since the year 1999--a review of evidence and perspectives. Rokholm B, Baker JL, Sørensen TI. Obes Rev. 2010 Dec.
The purpose was to investigate a possible levelling off in the obesity epidemic, by systematically reviewing literature and web-based sources. Eligible studies and data sources were required to have at least two measures of obesity prevalence since 1999. A literature and Internet search resulted in 52 studies from 25 different countries....

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Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Heid I et al. et al. Nat Genet. 2010 Oct 10.
Waist-hip ratio (WHR) is a measure of body fat distribution and a predictor of metabolic consequences independent of overall adiposity. WHR is heritable, but few genetic variants influencing this trait have been identified. We conducted a meta-analysis of 32 genome-wide association studies for WHR adjusted for body mass index (comprising up to 77,167 participants), following up 16 loci in an additional 29 studies (comprising up to 113,636 subjects)....

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Resequencing of 200 human exomes identifies an excess of low-frequency non-synonymous coding variants. Li Y et al. Nat Genet. 2010 Oct 3. . [OB Pedersen in LuCamp]
Targeted capture combined with massively parallel exome sequencing is a promising approach to identify genetic variants implicated in human traits. We report exome sequencing of 200 individuals from Denmark with targeted capture of 18,654 coding genes and sequence coverage of each individual exome at an average depth of 12-fold. On average, about 95% of the target regions were covered by at least one read. We identified 121,870 SNPs in the sample population, including 53,081 coding SNPs (cSNPs)....

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Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Speliotes EK, et al incl Loos RJ. Nat Genet. 2010 Oct 10.
Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ∼2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R,POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation....

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A genome-wide association study in the Japanese population identifies susceptibility loci for type 2 diabetes at UBE2E2 and C2CD4A-C2CD4B. Yamauchi T, et al Nat Genet. 2010 Sep 5.
We conducted a genome-wide association study of type 2 diabetes (T2D) using 459,359 SNPs in a Japanese population with a three-stage study design (stage 1, 4,470 cases and 3,071 controls; stage 2, 2,886 cases and 3,087 controls; stage 3, 3,622 cases and 2,356 controls)....

 

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Dietary determinants of changes in waist circumference adjusted for body mass index - a proxy measure of visceral adiposity. Romaguera D, Angquist L, Du H, Jakobsen MU, Forouhi NG, Halkjaer J, Feskens EJ, van der A DL, Masala G, Steffen A, Palli D, Wareham NJ, Overvad K, Tjønneland A, Boeing H, Riboli E, Sørensen TI. PLoS One. 2010 Jul.
Given the recognized health effects of visceral fat, the understanding of how diet can modulate changes in the phenotype "waist circumference for a given body mass index (WC(BMI))", a proxy measure of visceral adiposity, is deemed necessary. Hence, the objective of the present study was to assess the association between dietary factors and prospective changes in visceral adiposity as measured by changes in the phenotype WC(BMI....

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Twelve type 2 diabetes susceptibility loci identified through large-scale association analysis. Voight BF et al.; Nat Genet. 2010 Jul;42(7):579-89.
By combining genome-wide association data from 8,130 individuals with type 2 diabetes (T2D) and 38,987 controls of European descent and following up previously unidentified meta-analysis signals in a further 34,412 cases and 59,925 controls, we identified 12 new T2D association signals with combined P<5x10(-8)....

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MTNR1B G24E variant associates with BMI and fasting plasma glucose in the general population in studies of 22,142 Europeans. Andersson EA, Holst B, Sparsø T, Grarup N, Banasik K, Holmkvist J, Jørgensen T, Borch-Johnsen K, Egerod KL, Lauritzen T, Sørensen TI, Bonnefond A, Meyre D, Froguel P, Schwartz TW, Pedersen O, Hansen T. Diabetes. 2010 Jun;59(6):1539-48.
Common variants in the melatonin receptor type 1B (MTNR1B) locus have been shown to increase fasting plasma glucose (FPG) and the risk of type 2 diabetes. The aims of this study were to evaluate whether nonsynonymous variants in MTNR1B associate with monogenic forms of hyperglycemia, type 2 diabetes, or related metabolic traits....

 

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Reviews 

Obesity as a clinical and public health problem: is there a need for a new definition based on lipotoxicity effects? Sørensen TI, Virtue S, Vidal-Puig A.Biochim Biophys Acta. 2010 Mar;1801(3):400-4.
The risk functions for obesity (defined as the quantitative relation between degree of obesity throughout its range and the risk of health problems) have been used to define 'obesity' as an excess storage of fat in the body to such an extent that it causes health problems leading to increased mortality. The lipotoxicity theory implies that the fat stored in droplets of triglycerides in the cells are biologically inert and that the metabolic dysfunctions are primarily due to the increased exposure of the cells to fatty acids....

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