Exercise and Skeletal Muscle‐Derived Extracellular Vesicles: Their Cargo, Release, and Role in Metabolic Regulation

The health benefits of exercise are well established in the prevention and management of metabolic disorders such as obesity and diabetes. Emerging evidence indicates that extracellular vesicles (EVs) may contribute to the beneficial effects of exercise. These membrane-bound nanoparticles carry bioactive molecules, such as proteins, lipids, and RNAs, and facilitate intercellular communication. Of note, exercise has been shown to significantly influence EV release and cargo, enhancing their ability to mediate metabolic benefits across various tissue types. Recent investigations have demonstrated that skeletal muscle-derived EVs (SkM-EVs) can improve insulin sensitivity, promote glucose homeostasis, and modulate lipid metabolism in recipient cells and tissues. Additionally, exercise-induced SkM-EVs are enriched in specific proteins and microRNAs that activate key signaling pathways essential for glucose homeostasis, thereby providing protective effects against insulin resistance, inflammation, and other hallmarks of metabolic dysfunction. In this review, we summarise the current understanding of the effects of exercise on SkM-EV release, molecular cargo, and the potential mechanisms by which they exert metabolic benefits. By doing so, we highlight the potential of SkM-EVs as therapeutic tools for treating diabetes and related metabolic disorders.