FOR 5795:  HyperMet: Effects of skeletal muscle hypertrophy and atrophy on metabolic health

• Subject Area: Medicine ; Biology
• Term: since 2024
• Website: Homepage
• 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

Projects

• Coordination Funds (Applicant Wackerhage, Henning )
• HyperBone. Metabolic crosstalk between muscle, bone, and bone marrow adipocytes (Applicant Taipaleenmäki, Ph.D., Hanna )
• HyperCancer. Investigating the metabolic consequences of muscle-tumour interplay (Applicant Rohm, Maria )
• HyperEx. Effect of skeletal muscle hypertrophy and atrophy on metabolism, metabolite exchange and the organ fate of glucose (Applicants Kafka, André ;  Wackerhage, Henning )
• HyperICU. Effect of muscle wasting on global metabolite release and glucose homeostasis in patients with sarcopenia and critical illness (Applicants Blobner, Manfred ;  Wackerhage, Henning )
• HyperImaGene. Metabolic mechanisms that cause fat loss due to semaglutide versus muscle hypertrophy (Applicants Dragano, Ph.D., Nathalia ;  Hrabe de Angelis, Martin ;  Schilling, Franz )
• HyperSteroids. Effects of steroid hormone-related muscle hypertrophy and atrophy on systemic glucose homeostasis and adiposity (Applicants Dyar, Ph.D., Kenneth A. ;  Tokarz, Janina )
• P04 HyperPig. Metabolic health effects associated with muscle hypertrophy in pigs (Applicants Hinrichs, Arne ;  Wolf, Eckhard )
• S08 HyperFlux. Metabolic flux analysis to determine the effects of muscle hypertrophy and atrophy on metabolic health (Applicant Hiller, Karsten )
• S09 HyperGraph. Computational integration of molecular interactions to elucidate metabolic mechanisms of muscle hypertrophy and atrophy (Applicants Kastenmüller, Gabi ;  Lutter, Dominik )

• Spokesperson: Professor Dr. Henning Wackerhage