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

H. T. Wan, Y. G. Zhao, Xi WEI, K. Y. Hui, J. P. Giesy, Chris K C WONG*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

69 Citations (Scopus)

Abstract

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 β-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 - nonalcoholic fatty liver disease, environmental exposure to PFOS may attribute to the disease progression.

Original languageEnglish
Pages (from-to)1092-1101
Number of pages10
JournalBiochimica et Biophysica Acta - General Subjects
Volume1820
Issue number7
DOIs
Publication statusPublished - Jul 2012

Scopus Subject Areas

  • Biophysics
  • Biochemistry
  • Molecular Biology

User-Defined Keywords

  • β-oxidation
  • Fatty acid uptake
  • Lipid metabolism
  • Liver metabolism
  • Perfluorooctane sulfonate
  • Very-low density lipoprotein

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