Soybean‐Derived Exosome‐Like Nanovesicles Regulate Lipid Metabolism via Mitochondrial Biogenesis and UCP1/PGC‐1 <i>α</i> Mediated Thermogenesis

ABSTRACT Obesity has become an important public health concern in modern society. Plant‐derived exosome‐like nanovesicles are emerging as candidates for obesity intervention. The lipid‐lowering effect of soybean‐derived exosome‐like nanovesicles (SELNs) remains unknown. The aim is to explore the effect of SELNs on the lipid metabolism and its anti‐obesity mechanism. SELNs were isolated and characterized. Proteomic analysis showed that among the 1% top‐ranking proteins in SELNs, 173 proteins were predicted to be involved in the lipid metabolism. SELNs were stable in the stomach acid environment and ruptured in the intestinal fluid. SELNs boosted mitochondrial function and inhibited lipid droplet formation in sodium palmitate‐induced high‐fat Caenorhabditis elegans and palmitate‐induced HepG2 cells. The triglyceride content of differentiated 3T3‐L1 adipocytes was decreased when the dosage of SELNs increased. The key proteins/genes related to lipid metabolism of 3T3‐L1 adipocytes after SELNs pretreatment were analyzed by western blot and polymerase chain reaction. The data showed that SELNs significantly upregulated the uncoupling protein 1 (UCP‐1)‐mediated thermogenesis pathway, as well as lipolysis and fatty acid β ‐oxidation at 1 × 10 10 particles/mL. SELNs also promoted the mitochondrial biogenesis of adipocytes. In addition, protein cargos in SELNs play a vital role in inhibiting the lipid accumulation in adipocytes, not lipids or RNAs. These findings indicate that protein cargos in SELNs have the potential to regulate lipid metabolism, reduce lipid deposition, and improve the mitochondrial function of adipocytes. This study will provide a fundamental theory of SELNs for obesity intervention.