Koganti, Siva

Significance Skeletal muscle is increasingly recognized as a secretory organ. Revealing the identity and function of myokines can improve our understanding of skeletal muscle function under sedentary or exercise conditions, as well as its coordination with other organs, tissues, and overall body metabolism. This study identifies musclin as an exercise-responsive myokine critical for skeletal muscle adaptation to physical activity. We develop a musclin-encoding gene ( Ostn ) knockout mouse, which allows us to determine a previously unrecognized physiologic function of musclin in regulation of skeletal muscle mitochondrial biogenesis and physical endurance. The demonstrated molecular mechanism for musclin-dependent skeletal muscle adaptation to exercise also transforms the perspective on natriuretic peptide signaling, particularly as it relates to physical activity and exercise-induced remodeling in different tissues.