RMPC publications – University of Copenhagen

Food, Fitness & Pharma > Publications > RMPC publications

Publications from Rodent Metabolic Phenotyping Center

Rodent Metabolic Phenotyping Center is a core facility of the UNIK - Food, Fitness & Pharma initiative.

Follow the links below to read the full text and summaries of the scientific papers published by the Rodent Metabolic Phenotyping Center's scientists.

Original papers

Increased susceptibility to diet-induced obesity in GPRC6A receptor knockout mice J Endocrinol. Clemmensen C, Smajilovic S, Madsen AN, Klein AB, Holst B, Bräuner-Osborne H. 2013 Feb

The recently identified G protein-coupled receptor GPRC6A is activated by dietary amino acids and expressed in multiple tissues. Although the receptor is hypothesised 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 (DIO).

See full abstract

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.

See full abstract

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.

See full abstract

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. 2012 Oct

Reactive 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.

See full abstract

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. 2011 Dec 27

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. In addition, no studies have, to our knowledge, examined whether L: -Arg has beneficial effects as a dietary supplement in the mouse model. In the present study, we investigated the effects of L: -Arg supplementation to male C57BL/6 mice on an array of physiological parameters....

See full abstract

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....

See full abstract

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....

See full abstract

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.

See full abstract 

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....

See full abstract

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).... 

See full abstract 

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....

See full abstract

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....

See full abstract