{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T22:44:40Z","timestamp":1793832280738,"version":"4.6.1"},"reference-count":40,"publisher":"BMJ","issue":"12","funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["Gut"],"accepted":{"date-parts":[[2017,8,21]]},"published-print":{"date-parts":[[2018,12]]},"abstract":"<jats:sec>\n<jats:title>Objective<\/jats:title>\n<jats:p>\nAccumulation of free fatty acids (FFAs) in hepatocytes induces lipotoxicity, leading to non-alcoholic fatty liver disease (NAFLD). This study aimed to investigate the underlying mechanisms by which FFA contributes to the pathogenesis of NAFLD via the regulation of 3-mercaptopyruvate sulfurtransferase (MPST), a key enzyme that regulates endogenous hydrogen sulfide (H\n<jats:sub>2<\/jats:sub>\nS) biosynthesis.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design<\/jats:title>\n<jats:p>Hepatic MPST expression was evaluated in mice and patients with NAFLD. A variety of molecular approaches were used to study the effects of MPST regulation on hepatic steatosis in vivo and in vitro.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>\nIn vitro treatment of hepatocytes with FFAs upregulated MPST expression, which was partially dependent on NF-\u03baB\/p65. Hepatic MPST expression was markedly increased in high fat diet (HFD)-fed mice and patients with NAFLD. Partial knockdown of MPST via adenovirus delivery of MPST short hairpin RNA or heterozygous deletion of the\n<jats:italic>Mpst<\/jats:italic>\ngene significantly ameliorated hepatic steatosis in HFD-fed mice. Consistently, inhibition of MPST also reduced FFA-induced fat accumulation in L02 cells. Intriguingly, inhibition of MPST significantly enhanced rather than decreased H\n<jats:sub>2<\/jats:sub>\nS production, whereas MPST overexpression markedly inhibited H\n<jats:sub>2<\/jats:sub>\nS production. Co-immunoprecipitation experiments showed that MPST directly interacted with and negatively regulated cystathionine \u03b3-lyase (CSE), a major source of H\n<jats:sub>2<\/jats:sub>\nS production in the liver. Mechanistically, MPST promoted steatosis via inhibition of CSE\/H\n<jats:sub>2<\/jats:sub>\nS and subsequent upregulation of the sterol regulatory element-binding protein 1c pathway, C-Jun N-terminal kinase phosphorylation and hepatic oxidative stress.\n<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusions<\/jats:title>\n<jats:p>\nFFAs upregulate hepatic expression of MPST and subsequently inhibit the CSE\/H\n<jats:sub>2<\/jats:sub>\nS pathway, leading to NAFLD. MPST may be a potential therapeutic target for NAFLD.\n<\/jats:p>\n<\/jats:sec>","DOI":"10.1136\/gutjnl-2017-313778","type":"journal-article","created":{"date-parts":[[2017,9,7]],"date-time":"2017-09-07T03:13:57Z","timestamp":1504754037000},"page":"2169-2180","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":144,"title":["Fatty acids promote fatty liver disease via the dysregulation of 3-mercaptopyruvate sulfurtransferase\/hydrogen sulfide 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