Journal
JOURNAL OF HAZARDOUS MATERIALS
Volume 378, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jhazmat.2019.120766
Keywords
BDE 47; Obesity; Fatty liver; Lipidomics; Liver fibrosis; Oxidative stress
Categories
Funding
- National Key Research and Development Program of China [2017YFC1600505]
- National Natural Science Foundation of China [21577115, 21477101]
- Research Grant Council of Hong Kong [RGC GRF 463612, 14104314, 12300114]
- Hong Kong Baptist University [FRG2/15-16/067, FRG2/16-17/049, FRG2/17-18/072]
- Hong Kong Health and Medical Research Fund [HMRF/03144376]
- HKASO research grant 2015-16
- Mr. Kwok Yat Wai and Madam Kwok Chung Bo Fun Graduate School Development Fund, Hong Kong Baptist University
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Exposure to polybrominated diphenyl ethers (PBDEs), is closely associated with the occurrence of obesity and non-alcoholic fatty liver disease (NAFLD), yet their pathological effects and underlying mechanisms remain unclear. To examine the role of 2, 2', 4, 4'-tetrabromodiphenyl ether (BDE-47) in the progression of NAFLD under obese condition, male C57BL/6 J mice were fed with diet interaction for 15 weeks and subcutaneously injected with BDE-47 (7 mg/kg or 70 mg/kg) or the vehicle weekly. BDE-47 exposure (70 mg/kg) significantly elevated the body weight and worsened hepatic steatosis along with increased inflammation in high fat diet (HFD) fed mice. Furthermore, integration analysis of lipidomics and gene expression revealed that BDE-47 up-regulated triglyceride synthesis but suppressed lipid exportation and beta oxidation, aggravating the accumulation of hepatic lipid in HFD fed mice. In addition, the increase of liver fibrosis, serum transaminase levels, as well as lipid peroxidation have been observed in mice co-treated with BDE-47 and HFD. Moreover, BDE-47-induced fibrogenic responses in hepatocytes were suppressed by antioxidants, which confirmed that BDE-47-induced liver fibrosis was tightly associated with oxidative stress. In conclusion, these results provided new and robust evidence for revealing the hepatoxicity of BDE-47 under obese condition and illustrated the underlying mechanism of BDE-47 induced liver fibrosis.
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