HyperEx. Effect of skeletal muscle hypertrophy and atrophy on metabolism, metabolite exchange and the organ fate of glucose

• Applicants: Dr. Rainer Okrojek; Professor Dr. Henning Wackerhage
• Subject Area: Endocrinology, Diabetology, Metabolism
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 536691227

Global skeletal muscle hypertrophy commonly has anti-obesity and anti-diabetes effects, whereas global muscle atrophy worsens metabolic health. The aim of the project is to elucidate the underlying metabolic mechanisms using advanced methods of metabolic research on three levels. The three levels are intramuscular metabolism, metabolite exchange with the circulation, and inter-organ metabolism. First, we will use 13C stable isotope tracers to determine how hypertrophying and atrophying myotubes metabolize glucose, lactate, serine, valine, and taurine. We will also learn how these metabolites are used to generate biomass. In another experiment, we will perform a metabolic inhibitor screen to identify metabolic enzymes or transporters that limit muscle hypertrophy. Second, we will study how hypertrophying and atrophying human leg muscles alter their metabolite uptake and release when compared to leg muscles in a size steady state. Third, we will study in myotube-adipocyte co-culture and pigs how muscle hypertrophy (and atrophy in cell culture) alters the organ/cell fate of 13C glucose. This research will help to develop muscle-focused therapies for obesity and diabetes mellitus.

• DFG Programme: Research Units
• Subproject of: FOR 5795: HyperMet: Effects of skeletal muscle hypertrophy and atrophy on metabolic health
• Co-Investigator: Dr. Martin Schönfelder