Perfluorooctane sulfonate-induced hepatic steatosis in male sprague dawley rats is not attenuated by dietary choline supplementation

Bradford D. Bagley, Shu Ching Chang, David J. Ehresman, Alan Eveland, Jeremiah D. Zitzow, George A. Parker, Jeffrey M. Peters, Kendall B. Wallace, John L. Butenhoff

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100ppm PFOS fed to male mice and rats for 4 weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic choline:PFOS ion complex was hypothesized to cause this effect in mice. This study tested whether dietary choline supplementation attenuates PFOS-induced hepatic steatosis in rats. Sprague Dawley rats (12/sex/group) were fed control, choline supplemented (CS), 100ppm PFOS, or 100ppm PFOS + CS diets for 3 weeks. Male rats fed both PFOS-containing diets had decreased serum cholesterol and triglycerides (TGs) on days 9, 16, and/or 23 and increased hepatic free fatty acids and TG (ie, steatosis). Female rats fed both PFOS diets had decreased serum cholesterol on days 9 and 16 and decreased hepatic free fatty acid and TG at termination (ie, no steatosis). Liver PFOS concentrations were similar for both sexes. Liver choline concentrations were increased in male rats fed PFOS (±CS), but the increase was lower in the PFOS + CS group. Female liver choline concentrations were not altered by any diet. These findings demonstrate a clear sexrelated difference in PFOS-induced hepatic steatosis in the rat. Additional evaluated mechanisms (ie, nuclear receptor activation, mRNA upregulation, and choline kinase activity inhibition) did not appear to be involved in the hepatic steatosis. Dietary PFOS (100ppm) induced hepatic steatosis in male, but not female, rats that was not attenuated by choline supplementation. The mechanism of lipid accumulation and the sex-related differences warrant further investigation.

Original languageEnglish (US)
Pages (from-to)284-298
Number of pages15
JournalToxicological Sciences
Volume160
Issue number2
DOIs
StatePublished - Dec 1 2017

Keywords

  • Choline supplement
  • Liver
  • PFOS
  • Sex-related
  • Subacute

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