Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for four 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), 100 ppm PFOS, or 100 ppm PFOS + CS diets for three weeks. Male rats fed both PFOS-containing diets had decreased serum cholesterol and triglycerides (TG) on days 9, 16, and/or 23 and increased hepatic free fatty acids (FFA) and TG (i.e., steatosis). Female rats fed both PFOS diets had decreased serum cholesterol on days 9 and 16 and decreased hepatic FFA and TG at termination (i.e., 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 sex-related difference in PFOS-induced hepatic steatosis in the rat. Additional evaluated mechanisms (i.e., nuclear receptor activation, mRNA upregulation, and choline kinase activity inhibition) did not appear to be involved in the hepatic steatosis. Dietary PFOS (100 ppm) 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.
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Date of publication: 30 August 2017
Author information: Bradford D. Bagley (1); Shu-Ching Chang (1); David J. Ehresman (1); Alan Eveland (1); Jeremiah Zitzow (1); George A. Parker (2); Jeffrey M. Peters (3); Kendall B. Wallace (4); & John L. Butenhoff (5)
(1) Medical Department, 3M Company, Saint Paul, MN 55144, USA
(2) Charles River Laboratories, Durham, NC 27703, USA
(3)Department of Veterinary and Biomedical Sciences and The Center of Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, PA 16802, USA
(4)Department of Biomedical Sciences, University of Minnesota Duluth Medical School, Duluth, MN 55812, USA
(5) SaluTox LLC, Lake Elmo, MN 55042, USA