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
Dongdong Wu, Peiyu Zhong, Yizhen Wang, Qianqian Zhang, Jian‐Mei Li, Zhengguo Liu, Ailing Ji, Yanzhang Li
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.