title: PFOS-induced hepatic steatosis, the mechanistic actions on β-oxidation and lipid transport.
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.
  
  
  CONCLUSIONS
  Taken together, the disturbance of lipid metabolism leads to the accumulation of excessive fatty acids and triglycerides in hepatocytes.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Croucher Institute for Environmental Sciences, Department of Biology, Hong Kong Baptist University, 200 Waterloo Road, Kowloon Tong, Hong Kong, China. wanhinting@gmail.com
authors.forename: H T
authors.initials: HT
authors.lastname: Wan
authors.forename: Y G
authors.initials: YG
authors.lastname: Zhao
authors.forename: X
authors.initials: X
authors.lastname: Wei
authors.forename: K Y
authors.initials: KY
authors.lastname: Hui
authors.forename: J P
authors.initials: JP
authors.lastname: Giesy
authors.forename: Chris K C
authors.initials: CK
authors.lastname: Wong
mesh_terms: D017738:Alkanesulfonic Acids / Q000633:toxicity*; D000818:Animals; D001692:Biological Transport; D015153:Blotting, Western; D001835:Body Weight; D005227:Fatty Acids / Q000737:chemistry*; D005234:Fatty Liver / Q000139:chemically induced* / Q000378:metabolism*; D005466:Fluorocarbons / Q000633:toxicity*; D050356:Lipid Metabolism / Q000187:drug effects*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D009929:Organ Size; D010084:Oxidation-Reduction; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
chemical_list: D017738:Alkanesulfonic Acids; D005227:Fatty Acids; D005466:Fluorocarbons; D012333:RNA, Messenger; D014280:Triglycerides; C076994:perfluorooctane sulfonic acid