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

作者：Siu-Yi Leung, Ngan-Fong Ho, Chi‐Tang Ho, Min‐Hsiung Pan · 发表于：Journal of Agricultural and Food Chemistry · 年份：2025 · DOI：10.1021/acs.jafc.5c06392 · 被引用次数：5 · 研究领域：Bioactive Compounds in Plants、Atherosclerosis and Cardiovascular Diseases、Curcumin's Biomedical Applications

High Resolution Image Download MS PowerPoint Slide 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.