title: Editor's Highlight: Perfluorooctane Sulfonate-Choline Ion Pair Formation: A Potential Mechanism Modulating Hepatic Steatosis and Oxidative Stress in Mice.
abstract: The mechanisms underlying perfluorooctane sulfonate (PFOS)-induced steatosis remain unclear. The hypothesis that PFOS causes steatosis and other hepatic effects by forming an ion pair with choline was examined. C57BL/6 mice were fed either a control diet or a marginal methionine/choline-deficient (mMCD) diet, with and without 0.003, 0.006, or 0.012% potassium PFOS. Dietary PFOS caused a dose-dependent decrease in body weight, and increases in the relative liver weight, hepatic triglyceride concentration and serum markers of liver toxicity and oxidative stress. Some of these effects were exacerbated in mice fed the mMCD diet supplemented with 0.012% PFOS compared with those fed the control diet supplemented with 0.012% PFOS. Surprisingly, serum PFOS concentrations were higher while liver PFOS concentrations were lower in mMCD-fed mice compared with corresponding control-fed mice. To determine if supplemental dietary choline could prevent PFOS-induced hepatic effects, C57BL/6 mice were fed a control diet, or a choline supplemental diet (1.2%) with or without 0.003% PFOS. Lipidomic analysis demonstrated that PFOS caused alterations in hepatic lipid metabolism in the PFOS-fed mice compared with controls, and supplemental dietary choline prevented these PFOS-induced changes. Interestingly, dietary choline supplementation also prevented PFOS-induced oxidative damage. These studies are the first to suggest that PFOS may cause hepatic steatosis and oxidative stress by effectively reducing the choline required for hepatic VLDL production and export by forming an ion pair with choline, and suggest that choline supplementation may prevent and/or treat PFOS-induced hepatic steatosis and oxidative stress.
authors.affiliation: *Department of Veterinary and Biomedical Science and Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Limin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: *Department of Veterinary and Biomedical Science and Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Prasad
authors.initials: P
authors.lastname: Krishnan
authors.affiliation: Medical Department, 3M Company, St Paul, Minnesota.
authors.forename: David J
authors.initials: DJ
authors.lastname: Ehresman
authors.affiliation: The Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania.
authors.forename: Philip B
authors.initials: PB
authors.lastname: Smith
authors.affiliation: *Department of Veterinary and Biomedical Science and Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Mainak
authors.initials: M
authors.lastname: Dutta
authors.affiliation: Medical Department, 3M Company, St Paul, Minnesota.
authors.forename: Bradford D
authors.initials: BD
authors.lastname: Bagley
authors.affiliation: Medical Department, 3M Company, St Paul, Minnesota.
authors.forename: Shu-Ching
authors.initials: SC
authors.lastname: Chang
authors.affiliation: SaluTox, L.L.C, Lake Elmo, Minnesota.
authors.forename: John L
authors.initials: JL
authors.lastname: Butenhoff
authors.affiliation: *Department of Veterinary and Biomedical Science and Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802.
authors.forename: Andrew D
authors.initials: AD
authors.lastname: Patterson
authors.affiliation: *Department of Veterinary and Biomedical Science and Center for Molecular Toxicology and Carcinogenesis, The Pennsylvania State University, University Park, Pennsylvania 16802 jmp21@psu.edu.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Peters
mesh_terms: D017738:Alkanesulfonic Acids / Q000378:metabolism* / Q000633:toxicity; D000818:Animals; D002794:Choline / Q000378:metabolism* / Q000633:toxicity; D004305:Dose-Response Relationship, Drug; D005234:Fatty Liver / Q000139:chemically induced*; D005466:Fluorocarbons / Q000378:metabolism* / Q000633:toxicity; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018384:Oxidative Stress / Q000187:drug effects*
chemical_list: D017738:Alkanesulfonic Acids; D005466:Fluorocarbons; C076994:perfluorooctane sulfonic acid; D002794:Choline
keywords: choline; liver; mechanism; perfluorooctane sulfonate; steatosis