Food, Fitness & Pharma > Research > Fitness and Muscle

Fitness and Muscle

Main hypothesis:

Physical activity elicits its health promoting qualities and prevention of disease by activating specific molecular mechanisms within muscle as well as through cross-talk between muscle and other organs.

State of the art:

In Denmark, physical inactivity is considered the number two actual cause of death and physically inactive people have a life span which is 5 years shorter than physically active. Exercise elicits changes in gene expression, substrate oxidation, insulin sensitivity and turns on muscle as an endocrine organ.

Recent scientific advances have highlighted the role of signalling pathways and changes in gene expression in muscle and other tissues through which the beneficial effects of exercise arise. However, we need to generate more knowledge about the mechanisms whereby exercise mediates its health promoting effects.
 

This part of the UNIK is about:

• We will apply a unique research concept, in which we will perform in-depth mechanistic studies in humans, applying invasive techniques to secure arterial and venous blood samples and muscle and fat biopsies at rest and during exercise. To further unravel molecular mechanisms cell culture studies and genetically modified rodent models will be studied.

• Human studies will address the molecular mechanisms of ‘muscle signals’ and insulin sensitivity induced by diet composition, changes in energy status, physical activity and in-activity as well as gastric bypass surgery.

• Human studies will also address optimal dose-response effects of physical training in various groups with regard both to prophylaxis and treatment. 

• Human studies will address the effect of diet and physical activity that may be dependent on age, genetic disposition as well as the molecular mechanisms behind such effects.

• Animal models addressing the cellular, molecular and genetic mechanisms behind the effects of physical activity.
  

This part of the UNIK is expected to lead to:

• Identification of  the intracellular molecular and signalling pathways that mediate the effects of exercise in muscle and other tissues and unravel underlying mechanisms behind tissue interactions such as muscle-fat, muscle-pancreas, muscle-gut, muscle-liver and  muscle-brain cross-talk applying models.

• Elucidating how these mechanisms are optimally activated by various types of physical
  activity.

• Identification of the signalling mechanisms stimulating release of fatty acids and cytokines (adipokines) from adipose tissue during exercise and fasting;

• Establishing whether mutations affecting any of the signalling pathways involved in effects of exercise could predispose to Type 2 diabetes, obesity or the metabolic syndrome in humans;

• Characterization of the basis for the large individual variability in adaptation to repeated physical
  activity.

• Characterization of the interrelationships between diet, energy status and physical activity on insulin sensitivity and fat oxidation.

• Characterization of possible interactions between GI signals and muscle signals involved in prevention and curing of lifestyle diseases and the molecular mechanisms behind these effects 

• Delineation of patterns of expression of genes and proteins in humans at risk of developing Type 2 diabetes and in cohorts of monozygotic and dizygotic twins of known health status.

• Validation of potential new drug targets identified during the research, using small molecule inhibitors or activators, expression of constitutively active or dominant negative mutants, siRNA technology, or gene targeting. 

Impact/Implementation
Lifestyle recommendations, drug leads