Extracellular Vesicles in Nonalcoholic Fatty Liver Disease: Mechanisms and Therapeutic Opportunities

ABSTRACT Against the backdrop of the global rise in living standards, nonalcoholic fatty liver disease (NAFLD), a globally prevalent metabolic disorder, has become a major global health challenge. Its pathogenesis involves the intricate interplay of dysregulated lipid metabolism, inflammation, and fibrosis, underpinning the absence of targeted therapies. Extracellular vesicles (EVs), nanoscale mediators of intercellular communication, contribute to NAFLD progression by transporting bioactive molecules (proteins, nucleic acids, and lipids) for interorgan signaling, while holding therapeutic promise through targeting their biogenesis pathways. This review systematically summarizes how diverse EV cargos orchestrate metabolic imbalance, inflammatory responses, and fibrogenesis, while outlining emerging therapeutic strategies leveraging EVs as natural bioactives or drug delivery vectors. EVs exhibit stage‐dependent plasticity in origin and composition, mediating crosstalk among hepatocytes, adipocytes, and immune cells. Exploiting their biocompatibility and engineering potential, EVs can deliver anti‐inflammatory/antioxidant molecules or drugs targeting key signaling pathways. In conclusion, integrating multiomics analyses with advanced engineering approaches is critical to unravel EV‐mediated mechanisms and advance targeted therapies for NAFLD.