This review examines how skeletal muscle secretes bioactive factors (exerkines) during endurance exercise, defining a 'local-systemic secretome axis' that governs how these signals travel from muscle tissue to circulation.
The authors synthesize evidence from transcriptomics, proteomics, interstitial fluid, and extracellular vesicle studies to show that circulating exerkine levels are shaped by spatial organization, stimulus-specific programs, temporal dynamics, extracellular processing, and paracrine circuitry — not simple direct secretion from muscle.
As a narrative/expert review, it does not report original experimental data or effect sizes. Conclusions depend on the quality and heterogeneity of the synthesized studies.
Clinicians and researchers should not interpret circulating exerkine levels as straightforward proxies of muscle secretion — multiple regulatory layers intervene. This has direct implications for using exerkines as exercise biomarkers or therapeutic targets.
