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      Paradoxical Protective Effect of Perfluorooctanesulfonic Acid Against High Fat Diet Induced Hepatic Steatosis in Mice

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      International journal of toxicology

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          Abstract

          Perfluorooctanesulfonic acid (PFOS) is a persistent organic pollutant (POP) with worldwide bioaccumulation due to a very long half-life. PFOS exposure results in significant hepatic effects including steatosis, proliferation, hepatomegaly and in rodents, carcinogenesis. The objective of this study was to determine if PFOS exposure exacerbates nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) pathogenesis. Eight-week-old male C57BL/6J mice (n=5 per group) were fed ad libitum either normal chow diet (ND) alone, 60% high fat diet (HFD) alone, ND+PFOS and HFD+PFOS (0.0001% w/w (1mg/kg) of PFOS) for 6 weeks. Both HFD alone and the ND+PFOS treatment induced significant adiposity and hepatomegaly, but the HFD+PFOS treatment showed a marked protection. Oil Red O staining and quantitative analysis of hepatic lipid content revealed increased hepatic steatosis in ND+PFOS and in HFD alone fed mice, which was prevented in HFD+PFOS treatment. Further studies revealed that ND+PFOS treatment significantly affected expression of lipid trafficking genes to favor steatosis but these changes were absent in HFD+PFOS group. Specifically, expression of CD36, the major lipid importer in the cells, and PPARγ, its major regulator, were induced in HFD+NT and ND+PFOS-fed mice but remained unchanged in HFD+PFOS mice. In conclusion, these data indicate that co-administration of PFOS with HFD mitigates steatosis and hepatomegaly induced by HFD and that by PFOS fed in ND diet via regulation of cellular lipid import machinery. These findings suggest dietary lipid content be considered when performing risk management of PFOS in humans and the elucidation of PFOS induced hepatotoxicity.

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          Author and article information

          Journal
          9708436
          22231
          Int J Toxicol
          Int. J. Toxicol.
          International journal of toxicology
          1091-5818
          1092-874X
          16 July 2018
          22 August 2018
          Sep-Oct 2018
          01 September 2019
          : 37
          : 5
          : 383-392
          Affiliations
          Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, Kansas City, KS
          Author notes
          Corresponding Author: Udayan Apte, PhD, DABT, Department of Pharmacology, Toxicology and Therapeutics, University of Kansas Medical Center, 3901 Rainbow Blvd, MS1018, Kansas City, KS 66160, Tel: (913) 588-9247, uapte@ 123456kumc.edu
          Article
          PMC6150807 PMC6150807 6150807 nihpa979935
          10.1177/1091581818790934
          6150807
          30134762
          ed2134d8-2daa-4a54-ac55-9699e53f4add
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