Project Details
Projekt
HyperSteroids. Effects of steroid hormone-related muscle hypertrophy and atrophy on systemic glucose homeostasis and adiposity
Applicants
Kenneth A. Dyar, Ph.D.; Dr. Janina Tokarz
Subject Area
Endocrinology, Diabetology, Metabolism
Term
since 2024
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 536691227
Hypertrophy and atrophy of skeletal muscle and adipose tissue are controlled by opposing actions of sexually dimorphic steroid hormones like androgens and glucocorticoids. In men, androgens promote muscle hypertrophy, insulin sensitivity, and reduce adiposity. In contrast, androgens in women promote insulin resistance, and increase visceral adiposity and type 2 diabetes risk. High physiological or pharmacological levels of glucocorticoids promote muscle atrophy, impair insulin sensitivity, and increase adiposity. Molecular mechanisms mediating these effects are not yet fully elucidated. Both androgens and glucocorticoids play various genomic and non-genomic roles regulating skeletal muscle glucose uptake, but our understanding of this biology is incomplete. One important way steroid hormones control tissue metabolism is by regulating the number and coupling of ß-adrenergic receptors, thereby sensitizing tissues to the effects of catecholamines. While studies have established a clear bi-directional synergy between steroids and catecholamines, specific metabolic mechanisms for how this occurs remain largely unknown. In this project we will close these knowledge gaps using advanced methods of metabolic research. These include organ fate assays, arteriovenous metabolomics, and stable isotope metabolic flux analyses in skeletal muscles and adipose tissues from male and female mice, C2C12 myotubes, and primary myotubes during steroid-induced muscle hypertrophy (testosterone) and atrophy (corticosterone) compared to ß2-adrenergic-mediated hypertrophy. Since this biology is largely shared between mice and humans, we expect our project will help us understand precise metabolic mechanisms explaining how skeletal muscle hypertrophy and atrophy impacts metabolic health as a basis for future interventions in patients with e.g., obesity or type 2 diabetes mellitus.
DFG Programme
Research Units
