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ORIGINAL RESEARCH ARTICLE

Hydrogen sulfide ameliorates non-alcoholic fatty liver disease in mice

Hanyue Zhuang1† ,  Jiangzhe Si1† ,  Zewei Yang2 ,  Waner Wang2 ,  Zimo Ge2 ,  Yuhan Wang2 ,  Jingjing Li2 ,  Na Chen1* ,  Tieshan Teng1*
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1 Department of General Surgery, Huaihe Hospital of Henan University and School of Basic Medical Sciences, Henan University, Kaifeng, Henan, China
2 Faculty of Basic Medical Subjects, Zhengzhou Shuqing Medical College, Zhengzhou, Henan, China
GPD 2024, 3(3), 3409 https://doi.org/10.36922/gpd.3409
Submitted: 11 April 2024 | Accepted: 30 May 2024 | Published: 11 September 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Non-alcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive accumulation of intrahepatic fat and elevated hepatic metabolic enzyme levels, leading to hepatocellular vesicular steatosis. The global prevalence of this liver disease has been steadily increasing, closely associated with lifestyle factors such as obesity, hypertension, and hyperlipidemia. Notably, there is currently no approved pharmaceutical treatment for NAFLD. Hydrogen sulfide (H2S) is considered a vital gaseous signaling molecule in mammalian cells, playing a crucial role in various physiological and pathological processes. Numerous recent studies have demonstrated that H2S is involved in modulating a diverse array of biological functions. In vitro and in vivo research often utilizes various readily soluble organic or inorganic compounds H2S donors, such as sodium hydrosulfide, sodium sulfide, and GYY4137, which allow for controlled release and concentration adjustment of H2S, thereby facilitating the exploration of its biological effects and underlying mechanisms. Our findings indicate that H2S holds significant potential in reducing the accumulation of cellular lipid droplets and multiple lipid deposits, as evidenced by cellular and tissue staining, as well as triglyceride and total cholesterol assays. Subsequent transcriptomic analysis revealed a potential association between the degradation of lipid droplets by H2S and the activation of cellular autophagy. Validation through Western blotting in both cellular and animal models demonstrated that H2S effectively triggers autophagy through the AMP-activated protein kinase and mechanistic target of rapamycin pathway. This activation results in enhanced degradation of intracellular lipid content and decreased lipid accumulation in hepatocytes, ultimately ameliorating NAFLD in mice.

Keywords
Hydrogen sulfide
Non-alcoholic fatty liver disease
Autophagy
AMP-activated protein kinase and mechanistic target of rapamycin pathway
Funding
This research was funded by The Key R&D and Promotion Projects of Henan Province (232102311139); China Postdoctoral Science Foundation (2021m690095); National Innovation and Entrepreneurship Training Program for College Students (202310475169); and Henan University Research Laboratory Open Project for Undergraduate Students (20233001246 and 20233306208).
Conflict of interest
The authors declare no conflict of interest.
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