Nobiletin Modulates Adipocyte-Derived Exosomal miRNA to Improve Liver Lipid Metabolism in Obese Mice

This study examines the antiobesity properties of nobiletin through its influence on extracellular vesicles, particularly exosomes. Nob-ELVs (nobiletin with adipocyte-derived extracellular vesicles) significantly reduce fat accumulation in adipocytes without compromising cell viability. In vitro studies showed that introducing Nob-ELVs to 3T3-L1 preadipocytes led to marked reductions in fat accumulation. RNA sequencing indicated that Nobiletin alters the exosomal miRNA profile, downregulating miR-802-5p and others while upregulating miR-574-5p and related miRNAs. In a high-fat diet mouse model, Nob-ELVs prevented significant weight gain and improved food conversion efficiency. Mice receiving Nob-ELVs exhibited reduced hepatic lipid droplet accumulation and altered protein expressions, enhancing SIRT1 and FGF21 while suppressing ACC, FASN, and CD36. These findings suggest that Nob-ELVs inhibit fat accumulation and enhance lipid metabolism by modulating exosomal miRNAs, offering insights for new obesity treatment strategies.