Elucidating a Novel Exercise-Responsive Signaling Pathway for Metabolic Health in Muscle

• Applicant: Maximilian Kleinert, Ph.D.
• Subject Area: Endocrinology, Diabetology, Metabolism ; Anatomy and Physiology
• Term: from 2020 to 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 439290221

Skeletal muscle is the key organ for postprandial glucose disposal and insulin resistance of skeletal muscle is a major risk factor for the development of type 2 diabetes (T2D). Yet, skeletal muscle is an underappreciated organ in terms of the opportunity to prevent and treat metabolic diseases like T2D. This application tackles a novel aspect of skeletal muscle metabolism and biology to potentially identify new therapeutic molecular targets to treat metabolic diseases like T2D.Utilizing proteomics and phosphoproteomics, I have identified several novel exercise-responsive proteins that are conserved in human and mouse skeletal muscle. One of these is a protein called pantothenate kinase 4 (PanK4). Our preliminary work has demonstrated that PanK4 expression is enriched in skeletal muscle, that exercise activates PanK4 and that an increase in PanK4 abundance in muscle is sufficient to augment muscle glucose uptake. By taking advantage of three recently generated PanK4 loss-of-function mouse models, we will test the hypothesis that PanK4 is necessary for healthy muscle metabolism. This project has the potential to uncover a novel master regulator of skeletal muscle metabolism.

• DFG Programme: Research Grants