Lipid metabolism and lipid signaling in extracellular vesicles ontogeny: from biogenesis to functional execution.

This review explores the bidirectional relationship between lipids and extracellular vesicles (EVs) throughout the EV lifecycle. Lipid metabolism and lipid signaling influence EV biogenesis, cargo sorting, release, and targeting. EVs are key mediators of intercellular and interorgan communication. The cargoes carried by EVs can affect lipid metabolism and signaling pathways in target organs, thereby regulating diverse physiological and pathological processes. Recent studies indicate that EVs play critical roles in the pathological progression of various lipid metabolism-related diseases, such as obesity, type 2 diabetes (T2DM), non-alcoholic fatty liver disease (NAFLD), atherosclerosis, and cancer. Importantly, disease states induce characteristic alterations in the lipid composition of circulating EVs. These disease-specific EVs show great promise as non-invasive diagnostic biomarkers. As detailed in this review, understanding the intricate interplay between lipid metabolism, lipid signaling, and EV is essential for elucidating fundamental EV biology and developing novel EV-based diagnostic and therapeutic strategies.