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Browsing Chemical Sciences by Subject "acetyl-CoA"

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    The roles of H2S on hepatic acetyl-CoA and lipid metabolism
    (2020-07-13) Ali, Amr
    Hydrogen sulfide (H2S) is a novel gasotransmitter that is endogenously produced in the liver by cystathionine γ-lyase (CSE). The CSE/H2S system dysfunction has been linked to various liver diseases such as fatty liver diseases. Hepatic acetyl-CoA is a key intermediate from the metabolism of glucose, amino acid, and lipid in most species, but the roles of H2S in the regulation of hepatic acetyl-CoA and lipid metabolism have not been explored. Here, we found that incubation of human liver carcinoma (HepG2) cells with a mixture of free fatty acids (FFAs) or high glucose reduced CSE expression and H2S production and promoted intracellular accumulation of acetyl-CoA and lipid. Supply of exogenous NaHS (an H2S donor) or cysteine (an H2S precursor) reduced acetyl-CoA content and lipid accumulation, while blockage of CSE activity by DL-propargylglycine promoted intracellular lipid accumulation. Furthermore, H2S blocked FFAs-induced transcription of de novo lipogenesis, inflammation, and fibrosis-related genes. In vivo, knockout of CSE gene stimulated more hepatic acetyl-CoA and lipid accumulation in mice induced by high-fat choline-deficient diet. The expression of lipogenesis, inflammation, and fibrosis-related genes were significantly higher in liver tissue from CSE knockout mice when compared with wild-type mice. In conclusion, the CSE/H2S system is indispensable for maintaining the homeostasis of acetyl-CoA and lipid accumulation and protecting from the development of inflammation and fibrosis in liver under excessive caloric ingestion, and CSE/H2S system constitutes an interesting target for the prevention and treatment of fatty liver disease.