Unraveling the metabolic action of polyamines on muscle homeostasis in health & obesity

• Applicant: Dr. Mario Ost
• Subject Area: Nutritional Sciences
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 506215937

Metabolic disorders such as obesity are linked to an impaired skeletal muscle homeostasis and a decreased muscle insulin action, one of the earliest metabolic abnormality preceding type 2 diabetes onset, contributing to the etiology of obesity and the decline in metabolic health. Within the present proposal, I aim at testing the hypothesis that a muscle-specific polyamine metabolism is crucial for regulation of muscle metabolism and integrity, with particular focus on spermidine as the most abundant polyamine in a majority of different tissues, that upon supplementation induces autophagy processes. By following both (1) a basic scientific genetic and (2) a polyamine-targeted therapeutic approach, I will address how the muscle-specific spermidine action is coupled to glucose homeostasis and insulin sensitivity, mitochondrial integrity and redox signaling, autophagy mechanisms as well as endocrine muscle crosstalk. Further, I aim to understand how this connection is modified by nutritional stress under obesogenic conditions. The experimental set-up for a comprehensive metabolic and molecular profiling will involve in vivo mouse experiments and synergistic nutritional intervention studies, complemented by ex vivo investigations on intact mouse muscle fibers. Ultimately, this will shed new light on the importance of polyamine action in a tissue-specific as well as endocrine manner, and help to identify strategic target tissues of spermidine treatment to combat obesity-related metabolic dysfunctions.

• DFG Programme: Research Grants
• Major Instrumentation: Respirometer
• Instrumentation Group: 3060 Atemgas- und Blutgas-Analysatoren