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In recent years, the dietary structure of residents especially Chinese has gradually shifted to western dietary patterns. VC aggravates dietary fatty acid\u2010induced hepatic steatosis, but its mechanism is still unclear. And if the risk factors for steatosis persist, more severe diseases such as fibrosis and cirrhosis will occur. Therefore, we studied the effects and mechanisms of VC (160 and 800\u2009mg\/m<jats:sup>3<\/jats:sup>) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9\u00a0\u03bcM) on hepatic steatosis of high\u2010fat diet (HFD)\u2010fed mice and palmitic acid (PA, 100\u2009\u03bcM) treated HepG2 cells. Liver and serum biochemical indicators and pathological staining of the liver showed that the hepatic steatosis of VC combined with HFD groups was more severe than that of single\u2010exposure groups (HFD group, low\u2010dose VC group, and high\u2010dose VC group). Moreover, VC enhanced HFD\u2010induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element\u2010binding protein 1 (SREBP\u20101) and FAS. Besides, antioxidants and ERS inhibitors reduced the steatosis of HepG2 cells induced by VC metabolites and PA. These results suggest that VC exposure can enhance the degree of hepatic steatosis in HFD\u2010fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis\u2010related proteins, which may be related to the occurrence of hepatic steatosis. And the increased expression of CYP2E1 induced by VC combined with HFD may be the cause of OS.<\/jats:p>","DOI":"10.1002\/jat.4234","type":"journal-article","created":{"date-parts":[[2021,10,4]],"date-time":"2021-10-04T14:57:05Z","timestamp":1633359425000},"page":"490-505","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Mechanism of subchronic vinyl chloride exposure combined with a high\u2010fat diet on hepatic steatosis"],"prefix":"10.1002","volume":"42","author":[{"given":"Jin","family":"Jia","sequence":"first","affiliation":[{"name":"Department of Toxicology, School of Public Health Shanxi Medical University  Taiyuan China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi\u2010qi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Toxicology, School of Public Health Shanxi Medical University  Taiyuan 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