BACKGROUND: Metabolic diseases like type 2 diabetes and obesity share insulin resistance as a common feature, driven partly by mitochondrial dysfunction. Exercise-induced extracellular vesicles (EVs) have emerged as mediators of inter-organ communication in metabolic regulation. OBJECTIVE: To synthesize evidence on exercise-induced EVs in mitochondrial adaptation and insulin sensitivity, and propose an integrative framework linking EV-mediated communication to systemic metabolic benefits: METHODS: Narrative synthesis of mechanistic, animal, EV transfer/inhibition, translational, and human studies. RESULTS: -dependent, transcriptional, and post-transcriptional pathways to enhance mitochondrial biogenesis and oxidative metabolism. By improving substrate utilization and reducing lipotoxicity, mitochondrial ROS, ER stress, and inflammation, EV-mediated mitochondrial adaptation may boost insulin sensitivity and insulin signaling. EV transfer/inhibition studies support a contributory role for exercise-induced EVs in glucose homeostasis, though evidence remains context-dependent. CONCLUSIONS: Exercise-induced EVs may link exercise stimuli to mitochondrial adaptation and systemic insulin sensitivity. The proposed "exercise-EV-mitochondrial adaptation-insulin sensitivity" framework offers a conceptual basis for understanding systemic metabolic adaptation and highlights translational potential for metabolic diseases. Future work should clarify causality, tissue specificity, pharmacokinetics, and standardization.
Wang et al. (Sun,) studied this question.