Cross-Platform Transcriptomic Analysis of 40 Human and Rodent Skeletal Muscle Exerkines

Animal and human studies show that exercise induces organism-wide molecular adaptations that are partly mediated by exerkines which are secreted factors that enable inter-organ 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 including MetaMEx, Extrameta and the MoTrPAC 6-month-old rat training dataset. We reviewed exerkine-specific regulation in humans, mice and rats across acute and chronic exercise and inactivity. We determined conserved, non-conserved, and discordant exerkines across species and whether they were dependent on exercise modality or sex. Our review reveals substantial heterogeneity in skeletal muscle transcriptomic exerkine regulation with only a small subset showing conserved changes across species. Additionally, a key limitation is that our analysis was limited to transcriptomic data and may not reflect protein-level abundance, secretion, or uptake by recipient tissues. Therefore, we highlight a need for multi species and multi condition approaches when selecting exerkines as biomarkers or surrogate therapeutic targets.