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Gene & Protein in Disease





                                        ORIGINAL RESEARCH ARTICLE
                                        Hydrogen sulfide ameliorates non-alcoholic fatty

                                        liver disease in mice



                                        Hanyue Zhuang , Jiangzhe Si 1†  , Zewei Yang 2  , Waner Wang 2  , Zimo Ge 2  ,
                                                      1†
                                        Yuhan Wang 2  , Jingjing Li 2  , Na Chen * , and Tieshan Teng *
                                                                          1
                                                                                             1
                                        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



                                        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 (H S)
                                                                                                           2
                                        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 H S is involved in modulating a diverse array of biological
                                                              2
            † These authors contributed equally   functions. In vitro and in vivo research often utilizes various readily soluble organic
            to this work.               or inorganic compounds H S donors, such as sodium hydrosulfide, sodium sulfide,
                                                              2
            *Corresponding authors:     and GYY4137, which allow for controlled release and concentration adjustment
            Na Chen                     of H S, thereby facilitating the exploration of its biological effects and underlying
                                           2
            (48710532@qq.com)           mechanisms. Our findings indicate that H S holds significant potential in reducing
            Tieshan Teng                                                   2
            (10190136@vip.henu.edu.cn)  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.
            Citation: Zhuang H, Si J, Yang Z,
            et al. Hydrogen sulfide ameliorates   Subsequent transcriptomic  analysis revealed  a potential  association  between
            non-alcoholic fatty liver disease   the degradation of lipid droplets by H S and the activation of cellular autophagy.
                                                                        2
            in mice. Gene Protein Dis.   Validation through Western blotting in both cellular and animal models demonstrated
            2024;3(3):3409.
            doi: 10.36922/gpd.3409      that H S effectively triggers autophagy through the AMP-activated protein kinase
                                             2
                                        and mechanistic target of rapamycin pathway. This activation results in enhanced
            Received: April 11, 2024    degradation of intracellular lipid content and decreased lipid accumulation in
            Accepted: May 30, 2024
            Published Online: September 11,   hepatocytes, ultimately ameliorating NAFLD in mice.
            2024
            Copyright: © 2024 Author(s).   Keywords: Hydrogen sulfide; Non-alcoholic fatty liver disease; Autophagy;
            This is an Open-Access article
            distributed under the terms of the   AMP-activated protein kinase and mechanistic target of rapamycin pathway
            Creative Commons Attribution
            License, permitting distribution,
            and reproduction in any medium,
            provided the original work is
            properly cited.             1. Introduction
            Publisher’s Note: AccScience   Non-alcoholic fatty liver disease (NAFLD) is widely recognized as a prevalent chronic
            Publishing remains neutral with   liver disease, particularly in developed countries and in regions undergoing economic
            regard to jurisdictional claims in
            published maps and institutional   transition from poverty. The combined prevalence of NAFLD stands at approximately
                                            1
            affiliations.               25%.  The pathological progression of NAFLD can be classified into four distinct stages,


            Volume 3 Issue 3 (2024)                         1                               doi: 10.36922/gpd.3409
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