Hydrogen Sulfide Attenuates High-Fat Diet-Induced Non-Alcoholic Fatty Liver Disease by Inhibiting Apoptosis and Promoting Autophagy via Reactive Oxygen Species/Phosphatidylinositol 3-Kinase/AKT/Mammalian Target of Rapamycin Signaling Pathway

硫化氢通过活性氧/磷脂酰肌醇3-激酶/AKT/雷帕霉素靶蛋白信号通路抑制细胞凋亡并促进自噬,从而减轻高脂饮食诱导的非酒精性脂肪肝疾病。

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Abstract

Non-alcoholic fatty liver disease (NAFLD) is a common chronic liver disease worldwide. Hydrogen sulfide (H(2)S) is involved in a wide range of physiological and pathological processes. Nevertheless, the mechanism of action of H(2)S in NAFLD development has not been fully clarified. Here, the reduced level of H(2)S was observed in liver cells treated with oleic acid (OA). Administration of H(2)S increased the proliferation of OA-treated cells. The results showed that H(2)S decreased apoptosis and promoted autophagy through reactive oxygen species (ROS)-mediated phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) cascade in OA-treated cells. In addition, administration of H(2)S relieved high-fat diet (HFD)-induced NAFLD via inhibition of apoptosis and promotion of autophagy. These findings suggest that H(2)S could ameliorate HFD-induced NAFLD by regulating apoptosis and autophagy through ROS/PI3K/AKT/mTOR signaling pathway. Novel H(2)S-releasing donors may have therapeutic potential for the treatment of NAFLD.

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