Mechanism of subchronic vinyl chloride exposure combined with a high-fat diet on hepatic steatosis |
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Authors: | Jin Jia Shi-qi Chen Wei-zhe Pan Sheng-nan Yu Xiao-tian Zhao Yan Hao Yong-mei Shen Ying Cheng Cai-ling Wei Feng-jie Tian Xiao-yan Yan Yu-lan Qiu |
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Institution: | Department of Toxicology, School of Public Health, Shanxi Medical University, Taiyuan, China |
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Abstract: | 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/m3) and its metabolite (chloroacetaldehyde, 2.25, 4.5, and 9 μM) on hepatic steatosis of high-fat diet (HFD)-fed mice and palmitic acid (PA, 100 μM) 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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Keywords: | endoplasmic reticulum stress high-fat diet oxidative stress toxicant-associated steatohepatitis vinyl chloride |
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