PFOS-induced hepatic steatosis, the mechanistic actions on 尾-oxidation and lipid transport

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• 作者：H.T. Wan^a ; ^{wanhinting@gmail.com} ; Y.G. Zhao^a ; ^{08467234@hkbu.edu.hk} ; X. Wei^a ; ^{sissywei_wx@hotmail.com} ; K.Y. Hui^a ; ^{yuiiuh@hotmail.com} ; J.P. Giesy^b ; ^c ; ^d ; Chris K.C. Wong^a ; ^{ckcwong@hkbu.edu.hk}
• 关键词：Perfluorooctane sulfonate ; Lipid metabolism ; 尾-oxidation ; Fatty acid uptake ; Very-low density lipoprotein ; Liver metabolism
• 刊名：Biochimica et Biophysica Acta (BBA)/General Subjects
• 出版年：2012
• 期刊代码：16_03044165
• 类别：bio
• 出版时间：July, 2012
• 卷：1820
• 期：7
• 页码：1092-1101
• 文件大小：1255 K

摘要

Background

Perfluorooctane sulfonate (PFOS) was produced by various industries and was widely used in diverse consumer products. Human sample analysis indicated PFOS contamination in body fluids. Animal studies revealed that PFOS tends to accumulate in livers and is able to induce hepatomegaly. However the underlying mechanism of PFOS-elicited hepatotoxicity has not yet been fully addressed. The objective of this study is to identify the cellular target of PFOS and to reveal the mechanisms of PFOS-induced toxicity.

Methods

In this study, mature 8-week old male CD-1 mice were administered 0, 1, 5 or 10 mg/kg/day PFOS for 3, 7, 14 or 21 days. Histological analysis of liver sections, and biochemical/molecular analysis of biomarkers for hepatic lipid metabolism were assessed.

Results

PFOS-induced steatosis was observed in a time- and dose-dependent manner. The gene expression levels of fatty acid translocase (FAT/CD36) and lipoprotein lipase (Lpl) were significantly increased by 10 and/or 5 mg/kg PFOS. Serum levels of very-low density lipoprotein were decreased by 14 days of PFOS exposure (p < 0.05). The rate of mitochondrial 尾-oxidation was also found to be significantly reduced, leading to the restriction of fatty acid oxidation for energy production.

Conclusion

Taken together, the disturbance of lipid metabolism leads to the accumulation of excessive fatty acids and triglycerides in hepatocytes.

General significance

Since PFOS-elicited pathological manifestation resembles one of the most common human liver diseases鈥攏onalcoholic fatty liver disease, environmental exposure to PFOS may attribute to the disease progression.