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

• Published in: Biochimica et biophysica acta 2012-07, Vol.1820 (7), p.1092-1101
• Main Authors: Wan, H.T., Zhao, Y.G., Wei, X., Hui, K.Y., Giesy, J.P., Wong, Chris K.C.
• Format: Article
• Language: English
• Subjects: Alkanesulfonic Acids - toxicity; Animals; beta oxidation; Biological Transport; biomarkers; blood serum; Blotting, Western; Body Weight; disease course; dose response; energy; environmental exposure; Fatty acid uptake; fatty acids; Fatty Acids - chemistry; fatty liver; Fatty Liver - chemically induced; Fatty Liver - metabolism; Fluorocarbons - toxicity; gene expression; hepatocytes; hepatotoxicity; humans; industry; Lipid metabolism; Lipid Metabolism - drug effects; lipoprotein lipase; lipoproteins; liver; Liver - drug effects; Liver - metabolism; Male; males; Mice; Organ Size; Oxidation-Reduction; Perfluorooctane sulfonate; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger - genetics; triacylglycerols; Triglycerides - metabolism; Very-low density lipoprotein; β-oxidation
• ISSN: 0304-4165; 0006-3002; 1872-8006
• DOI: 10.1016/j.bbagen.2012.03.010

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