Transcriptomic analysis of 40 human and rodent skeletal muscle exerkines

Animal and human studies show that exercise induces organism wide molecular adaptations, many of which are mediated by exerkines which are secreted factors that enable communication between tissues such as skeletal muscle, adipose tissue, liver and the brain. However, the tissue specific responsiveness of individual exerkines and how these responses differ across species, exercise conditions and sexes remain poorly understood. To address this gap, we systematically analyzed skeletal muscle transcriptomic responses of 40 exerkines using three publicly available datasets which include MetaMEx, Extrameta and the MoTrPAC rat training study. We analyzed exerkine specific regulation in humans, mice and rats across acute and chronic exercise as well as inactivity, and determined which responses were conserved, species specific, sex dependent or dependent on exercise duration. Our analysis reveals substantial heterogeneity in skeletal muscle exerkine regulation with only a small subset showing conserved changes across species, while many exerkines exhibited human exclusive, rodent exclusive, acute specific or chronic specific patterns. These results provide a ranked overview of the most exercise responsive skeletal muscle exerkines and highlight the need for multi species and multi condition approaches when selecting exerkines as biomarkers or therapeutic targets.