Extracellular Vesicle-Mediated Local and Systemic Communication in Metabolic Diseases.

Extracellular vesicles (EVs) have emerged as key mediators of intercellular communication, shuttling bioactive proteins, lipids, and nucleic acids between organs to maintain metabolic homeostasis. In this review, we provide an overview of recent advances in EV-mediated local and systemic communication across four interconnected metabolic diseases: diabetes, obesity, metabolic dysfunction-associated steatotic liver disease (MASLD), and sarcopenia, with a focus on the mechanistic roles of EVs in disease onset, adaptation, and progression. We highlight how EVs from the pancreas, adipose tissue, liver, and skeletal muscle propagate metabolic dysfunction across organs, and identify some shared cargo signatures, including miR-27a, miR-155, miR-146a-5p, miR-690, CXCL10, RBP4, ceramides, adipokine composition, and mitochondrial components, which may represent common pathogenic mechanisms. Current EV-based therapeutic strategies are discussed, and future efforts should prioritize the standardization of EV isolation and characterization to improve reproducibility, thereby facilitating clinical translation.