Extracellular Vesicles Derived from Adipose Tissue Macrophages in Obesity: Functional Heterogeneity and miRNA-Mediated Regulation of Skeletal Muscle Insulin Sensitivity

Remodeling of adipose tissue macrophages (ATMs) during obesity is closely linked to insulin resistance. In addition to soluble mediators, extracellular vesicles (EVs) released by ATMs and their microRNA (miRNA) cargo have been implicated in metabolic communication between adipose tissue and skeletal muscle. Previous studies have shown that EV cargo profiles and metabolic effects can vary across ATM states, adipose depots, and macrophage populations, with some EVs promoting insulin resistance and others improving insulin sensitivity. Among the mechanisms relevant to skeletal muscle, the miR-29a–PPARδ relationship has relatively direct experimental support from ATM-EV studies. The miR-210-3p–GLUT4 relationship is supported by changes in ATM-EV cargo, findings from myocytes and other recipient-cell models, and experiments involving exogenously administered macrophage EVs. However, this relationship has not been fully validated within a single ATM-EV–skeletal muscle experimental system. Studies involving miR-690 also suggest that EVs from certain macrophage populations can improve insulin sensitivity, although the molecular annotation of miR-690, its reported direct targeting mechanism, and the applicability of these findings to humans remain under debate. Overall, these findings implicate ATM-derived EVs in metabolic regulation, while their physiological effects on skeletal muscle in humans remain uncertain.