Resveratrol Attenuates High-Fat Diet–Induced Hepatic Lipotoxicity by Upregulating Bmi-1 Expression

作者：Weigang Yuan, Mi Zhang, Chunxu Wang, Bin Li, Lei Li, Feng Ye, Chuanrui Xu · 发表于：Journal of Pharmacology and Experimental Therapeutics · 年份：2022 · DOI：10.1124/jpet.121.001018 · 被引用次数：23 · 研究领域：Liver Disease Diagnosis and Treatment、Genomics, phytochemicals, and oxidative stress、Sirtuins and Resveratrol in Medicine

Resveratrol (RES), a natural polyphenol phytoalexin, has been reported to attenuate nonalcoholic fatty liver disease (NAFLD). However, its roles on protection of liver from lipotoxicity and underlying mechanism are not fully understood. In this study, we investigated the impacts of RES on alleviating hepatic lipotoxicity and corresponding molecular mechanism. Impacts of RES on oleic acid (OA)-induced lipotoxicity were assessed in L02 cells and C57BL/6J mice, respectively. In L02 cells, lipotoxicity was assessed by detection of apoptosis, mitochondrial function, oxidative stress and ROS-related signaling. In mice, lipotoxicity was evaluated by detecting hepatic function, serum enzyme activity, and reactive oxygen species (ROS) levels. We found that RES reduced OA-induced apoptosis, mitochondrial dysfunction, ROS generation, and DNA damage in L02 cells. RES also decreased expression of cleaved caspase-3 and p53 and increased expression of B-cell lymphoma 2 (Bcl-2). Importantly, RES protected mice from high-fat diet-induced hepatic lipotoxicity, demonstrated by reduced ROS levels and lipid peroxidation. Mechanically, B lymphoma Mo-MLV insertion region 1 (Bmi-1) expression and antioxidative superoxide dismutase were increased after RES treatment. Further mechanistic analysis indicated that protection effects of RES against OA-induced lipotoxicity were abrogated by Bmi-1 small interference RNA (siRNA) in L02 cells. SIGNIFICANCE STATEMENT: Results from clinical studies about the ef...