期刊
JOURNAL OF APPLIED TOXICOLOGY
卷 42, 期 3, 页码 490-505出版社
WILEY
DOI: 10.1002/jat.4234
关键词
endoplasmic reticulum stress; high-fat diet; oxidative stress; toxicant-associated steatohepatitis; vinyl chloride
类别
资金
- Natural Science Foundation for Young Scientists of Shanxi Province, China [201901D211327]
- National Natural Science Foundation of China [81773405]
- Shanxi Scholarship Council of China [2016-056]
The study found that exposure to vinyl chloride can exacerbate hepatic steatosis in high-fat diet mice, leading to oxidative stress and endoplasmic reticulum stress. Upregulation of de novo lipogenesis-related proteins expression may be associated with the occurrence of hepatic steatosis.
Vinyl chloride (VC) is a common industrial organic chlorine and environmental pollutant. In recent years, the dietary structure of residents especially Chinese has gradually shifted to western dietary patterns. VC aggravates dietary fatty acid-induced 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 mg/m(3)) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 mu M) on hepatic steatosis of high-fat diet (HFD)-fed mice and palmitic acid (PA, 100 mu M) 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-exposure groups (HFD group, low-dose VC group, and high-dose VC group). Moreover, VC enhanced HFD-induced oxidative stress (OS) and endoplasmic reticulum stress (ERS) and further upregulated the expression of sterol regulatory element-binding protein 1 (SREBP-1) 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-fed mice. VC combined with HFD led to OS and ERS and upregulated the expression of de novo lipogenesis-related 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.
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