Oleic acid protects saturated fatty acid mediated lipotoxicity in hepatocytes and rat of non-alcoholic steatohepatitis

Aim This study aims to demonstrate the protective effects of monounsaturated oleic acid (OA) against saturated palmitic acid (PA) induced cellular lipotoxicity in hepatocytes and rats with non-alcoholic steatohepatitis (NASH). Main methods Human hepatoma cell line HepG2 cells and neonatal rat primary hepatocytes were treated with PA or/and OA for 24 h. SD rats were fed with high fat diet (HFD) to induce NASH. From the 16th w, the HFD was full or half replaced by olive oil to observe the protective effects. Key findings In vitro, OA substantially alleviated PA induced cellular apoptosis, oxidative stress, ER stress, mitochondrial dysfunction, as well as inflammation in hepatocytes. In vivo, only olive oil supplementation had no detrimental effects, while HFD developed NASH in normal rats. Full replacement of HFD with olive oil had profoundly reversed NASH. Noteworthily, half replacement of HFD with olive oil (a mixed diet) has ameliorated NASH injury as well. It strikingly changed the hepatic histology from macrovesicular-steatosis into entire microvesicular-steatosis, and significantly reduced inflammation, ballooning and fibrosis. Significance Our study has demonstrated in both hepatocytes and NASH rats that oleic acids had great potential to combat the saturated fatty acids induced hepatic lipotoxicity. Only half replacement of HFD by monounsaturated fatty acids rich diet still had significant therapeutic outcome in NASH rats. Redirecting the toxic saturated fatty acids into triglyceride storage and reduction of cholesterol accumulation might be the possible explanation of OA driven protection in this scenario.