Oleuropein mitigates non-alcoholic fatty liver disease (NAFLD) and modulates liver metabolites in high-fat diet-induced obese mice via activating PPARα

BACKGROUND: This study aimed to elucidate the mechanism of oleuropein (OLE) ameliorates non-alcoholic fatty liver disease (NAFLD) and its underlying mechanisms. RESULTS: Male C57BL/6J mice were fed either a low-fat diet (LFD), a high-fat diet (HFD), or a HFD supplemented with 0.03% (w/w) OLE for 16 weeks. OLE supplementation decreased body weight and liver weight, improved serum lipid profiles, and ameliorated HFD-induced hepatic dysfunction. Liver metabolomics analysis revealed that OLE increased the levels of nicotinamide, tauroursodeoxycholic acid, taurine, and docosahexaenoic acid, which were beneficial for lipid homeostasis and inflammation regulation. OLE exerted its protective effects by activating peroxisome proliferator-activated receptor alpha (PPAR alpha), a key transcription factor that regulates fibroblast growth factor 21 (FGF21) expression and modulates lipid oxidation, lipogenesis and inflammation pathways. Importantly, OLE supplementation did not significantly affect body weight or liver weight in PPAR alpha knockout (PPAR alpha KO) mice, indicating that PPAR alpha is essential for OLE-mediated NAFLD prevention. CONCLUSION: Our results suggest that OLE alleviates NAFLD in mice by activating PPAR alpha and modulating liver metabolites. (c) 2024 Society of Chemical Industry.