Project Details
Projekt
Coordination Funds
Applicant
Professor Dr. Henning Wackerhage
Subject Area
Endocrinology, Diabetology, Metabolism
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 536691227
Global skeletal muscle hypertrophy is associated with a loss of fat mass, improved glucose homeostasis, higher bone mineral density and may improve cancer outcomes. In contrast, skeletal muscle atrophy e.g., because of ageing (sarcopenia), immobilisation, cancer cachexia or critical illness has opposite effects. Most current research focuses on the DNA-RNA-protein system e.g., by identifying myokines such as myostatin or FGF21. However, there is little research that seeks to elucidate metabolic mechanisms using metabolic research methods. The aim of the HyperMet research unit is to use advanced methods of metabolic research to study how muscle hypertrophy and atrophy affect metabolic health. We will study this on three levels: 1) intramuscular metabolism, 2) metabolite exchange with the circulation, and 3) inter-organ metabolism. Specifically, P01 HyperEx will investigate how muscle hypertrophy and atrophy affect the metabolism of glucose, lactate, serine, valine, and taurine as well as the changes of metabolite exchange induced by resistance training-induced muscle hypertrophy and immobilisation-induced atrophy. It will also study how muscle hypertrophy affects the inter-organ metabolism of 13C glucose. P02 HyperBone focuses on the inter-organ metabolism of muscle, bone, and bone marrow fat to explain links between muscle mass and bone density. P03 HyperSteroid will investigate metabolic effects of steroid hormones that can either promote skeletal muscle hypertrophy or atrophy on fat and glucose homeostasis. P04 HyperPig will investigate how e.g., myostatin deficiency-induced muscle hypertrophy affects the metabolite exchange between muscle, fat, and other organs. The pig model is ideal for this, as the supplying arteries and draining veins of the respective tissues can be punctured to measure metabolite uptake and release. P05 HyperImaGene will compare the fat loss and muscle atrophy induced by semaglutide (Wegovy) with the fat loss, but muscle hypertrophy induced by myostatin deficiency. The project will especially use metabolic imaging for longitudinal analyses of the treated mice. P06 HyperCancer will study "inter-organ" metabolism between muscle and tumours in mice and humans with cancer cachexia. P07 HyperICU will study the metabolite exchange between muscle and blood as well as glucose metabolism in sarcopenia and critical illness. It also seeks to start developing a test for anabolic resistance. S08 HyperFlux is a service project that offers metabolic flux analysis using stable isotope-labelled tracers. S09 HyperGraph is a second service project that will analyse, synthesize, and visualize the data generated. Together, the HyperMet research unit will establish a critical mass of researchers that collaboratively use advanced methods of metabolic research and may contribute to muscle-focused treatments and interventions for diseases such as obesity, diabetes, osteoporosis, and cancer that affect billions of people.
DFG Programme
Research Units
