Effects of treatment with hydrogen sulfide on methionine‐choline deficient diet‐induced non‐alcoholic steatohepatitis in rats

Luo, Zhu-lin; Tang, Lijun; Wang, Tao; Dai, Ruiwu; Ren, Jiandong; Cheng, Long; Ke, Xiang; Tian, Fanghua

doi:10.1111/jgh.12389

Cited by 50 publications

(55 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Free fatty acid incubation of HepG2 cells in vitro resulted in swollen mitochondria with increased inner matrix density and loss of cristae (Jun et al, 2011). It was found that MCD-diet induced hepatic mitochondrial dysfunction marked by enhanced reactive oxygen species formation (Luo et al, 2014) and reduced activities of Complexes I and II in this study.…”

Section: Discussionmentioning

confidence: 85%

See 1 more Smart Citation

Treatment with baicalein attenuates methionine−choline deficient diet-induced non-alcoholic steatohepatitis in rats

Xin

Zhang

et al. 2014

European Journal of Pharmacology

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 85%

“…MCD-diet led to an increased production of reactive oxygen species and at the same time decreased the activity of antioxidant enzymes (Jorgacevic et al, 2013;Luo et al, 2014). Free fatty acid incubation of HepG2 cells in vitro resulted in swollen mitochondria with increased inner matrix density and loss of cristae (Jun et al, 2011).…”

Section: Discussionmentioning

confidence: 96%

Treatment with baicalein attenuates methionine−choline deficient diet-induced non-alcoholic steatohepatitis in rats

Xin

Zhang

et al. 2014

European Journal of Pharmacology

View full text Add to dashboard Cite

“…H 2 S has been shown to be protective against NAFLD (25,32). NaHS prevents nonalcoholic steatohepatitis induced by a methionine-choline-deficient diet in rats by suppressing oxidative stress and inflammation (25). Very recently, Wu et al (37) found that NaHS mitigated the fatty liver in obese mice through antioxidant potential.…”

Section: E931mentioning

confidence: 99%

“…Conversely, TG accumulating in the liver leads to NAFLD. H 2 S has been shown to be protective against NAFLD (25,32). NaHS prevents nonalcoholic steatohepatitis induced by a methionine-choline-deficient diet in rats by suppressing oxidative stress and inflammation (25).…”

Section: E931mentioning

confidence: 99%

See 1 more Smart Citation

Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway

Sun

Zhang

et al. 2015

American Journal of Physiology-Endocrinology and Metabolism

113

View full text Add to dashboard Cite

. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway. Am J Physiol Endocrinol Metab 309: E925-E935, 2015. First published October 6, 2015; doi:10.1152/ajpendo.00294.2015.-Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPK␣2 Ϫ/Ϫ mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPKmTOR pathway. hydrogen sulfide; triglyceride; NAFLD; autophagy; AMPK HYPERTRIGLYCERIDEMIA (HTG) is the most common lipid metabolism disorder and is an important independent risk factor for cardiovascular and cerebrovascular diseases (2, 10, 29). The liver plays a cardinal role in lipid metabolism. Increased production and/or decreased clearance of triglyceride (TG) in the liver inevitably results in HTG (13, 30), while TG accumulation in the liver can lead to nonalcoholic fatty liver disease (NAFLD) (40). NAFLD is the most prevalent chronic liver disease in the developed world and is an important risk factor for the development of liver fibrosis and cirrhosis and predisposes to the development of hepatocellular carcinoma (1, 26).Recent research suggests that autophagy participates in the regulation of liver lipid metabolism (5, 33, 34). Autophagy modulates hepatocyte lipid metabolism through lipophagy, which involves sequestration of lipid drops in double-membrane autophagosomes, followed by fusion with lysosomes to form autolysosomes, and subsequent degradation of TG by lipases within the autolysosomes. Reduction of liver cell autophagic activity causes decreased lipolysis and provokes free fatty acid (FFA) ␤-oxidation, resulting in hepatic steatosis and often progresses to NAFLD and HTG (34).AMP-activated pro...

show abstract

Hydrogen Sulfide Alleviates Liver Injury Through the S‐Sulfhydrated‐Kelch‐Like ECH‐Associated Protein 1/Nuclear Erythroid 2–Related Factor 2/Low‐Density Lipoprotein Receptor–Related Protein 1 Pathway

Zhao

Song

et al. 2021

Hepatology

View full text Add to dashboard Cite

Background and Aims Protein S‐sulfhydration mediated by H2S has been shown to play important roles in several diseases. However, its precise role in liver disease and the related mechanism remain unclear. Approach and Results We showed that in streptozotocin (STZ)–treated and high‐fat diet (HFD)–treated low‐density lipoprotein receptor–negative (LDLr−/−) mice, the H2S donor GYY4137 ameliorated liver injury, decreased serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, mitigated lipid deposition, and reduced hepatocyte death. Strikingly, S‐sulfhydration of Kelch‐like ECH‐associated protein 1 (Keap1) was decreased in the livers of patients with fatty liver under diabetic conditions. In STZ+HFD‐treated LDLr−/− mice and in high glucose–treated and oxidized low‐density lipoprotein (ox‐LDL)–treated primary mouse hepatocytes, the GYY4137‐mediated increase in Keap1 S‐sulfhydration induced nuclear erythroid 2‐related factor 2 (Nrf2) dissociation from Keap1, which enhanced the nuclear translocation of Nrf2 itself and the consequent expression of antioxidant proteins. Keap1 Cys151 mutation significantly reduced Keap1 S‐sulfhydration and abolished the hepatoprotective effects of H2S both in vivo and in vitro. Nrf2 deficiency inhibited the H2S‐induced beneficial impacts in Nrf2−/− mice. Similarly, in CCl4‐stimulated mice, GYY4137 increased Keap1 S‐sulfhydration, improved liver function, alleviated liver fibrosis, decreased hepatic oxidative stress, and activated the Nrf2 signaling pathway; and these effects were abrogated after Keap1 Cys151 mutation. Moreover, H2S increased the binding of Nrf2 to the promoter region of LDLr‐related protein 1 (Lrp1) and consequently up‐regulated LRP1 expression, but these effects were disrupted by Keap1 Cys151 mutation. Conclusions H2S‐mediated Keap1 S‐sulfhydration alleviates liver damage through activation of Nrf2. Hence, administration of exogenous H2S in the form of the H2S donor GYY4137 may be of therapeutic benefit in the context of concurrent hyperlipidemia and hyperglycemia–induced or CCl4‐stimulated liver dysfunction.

show abstract

Effects of treatment with hydrogen sulfide on methionine‐choline deficient diet‐induced non‐alcoholic steatohepatitis in rats

Abstract: Treatment with H2 S prevented NASH induced by MCD diet in rats possibly through abating oxidative stress and suppressing inflammation.

Cited by 50 publications

References 43 publications

Treatment with baicalein attenuates methionine−choline deficient diet-induced non-alcoholic steatohepatitis in rats

Treatment with baicalein attenuates methionine−choline deficient diet-induced non-alcoholic steatohepatitis in rats

Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway

Hydrogen Sulfide Alleviates Liver Injury Through the S‐Sulfhydrated‐Kelch‐Like ECH‐Associated Protein 1/Nuclear Erythroid 2–Related Factor 2/Low‐Density Lipoprotein Receptor–Related Protein 1 Pathway

Contact Info

Product

Resources

About