Chronic exposure to tetrabromodiphenyl ether (BDE-47) aggravates hepatic steatosis and liver fibrosis in diet-induced obese mice.

Abstract

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 β 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.

• Authors: Chunxue Yang, Lin Zhu, Qingzheng Kang, Hin Kiu Lee, Dapeng Li, Arthur C K Chung, Zongwei Cai
• Journal: Journal of hazardous materials (J Hazard Mater) Vol. 378 Pg. 120766 (10 15 2019) ISSN: 1873-3336 [Electronic] Netherlands
• PMID: 31226595 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Antioxidants
• Blood Glucose
• Halogenated Diphenyl Ethers
• 2,2',4,4'-tetrabromodiphenyl ether

Topics

• Animals
• Antioxidants (chemistry)
• Blood Glucose
• Body Weight
• Diet
• Diet, High-Fat
• Fatty Liver (chemically induced)
• Fibrosis
• Halogenated Diphenyl Ethers (toxicity)
• Hepatocytes (drug effects)
• Inflammation (metabolism)
• Lipid Metabolism
• Lipid Peroxidation
• Lipidomics
• Liver (drug effects)
• Liver Cirrhosis (chemically induced)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Obese
• Obesity (complications)
• Oxidative Stress