Perfluorooctane sulfonate-choline ion pair formation: A potential mechanism modulating hepatic steatosis and oxidative stress in mice

Limin Zhang, Prasad Krishnan, David J. Ehresman, Philip B. Smith, Mainak Dutta, Bradford D. Bagley, Shu Ching Chang, John L. Butenhoff, Andrew David Patterson, Jeffrey Maurice Peters

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish (US)
Article numberkfw120
Pages (from-to)186-197
Number of pages12
JournalToxicological Sciences
Volume153
Issue number1
DOIs
StatePublished - Sep 1 2016

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Oxidative stress
Choline
Oxidative Stress
Ions
Liver
Nutrition
Diet
Methionine
perfluorooctane sulfonic acid
Inbred C57BL Mouse
Dietary Supplements
Lipid Metabolism

All Science Journal Classification (ASJC) codes

  • Toxicology

Cite this

Zhang, Limin ; Krishnan, Prasad ; Ehresman, David J. ; Smith, Philip B. ; Dutta, Mainak ; Bagley, Bradford D. ; Chang, Shu Ching ; Butenhoff, John L. ; Patterson, Andrew David ; Peters, Jeffrey Maurice. / Perfluorooctane sulfonate-choline ion pair formation : A potential mechanism modulating hepatic steatosis and oxidative stress in mice. In: Toxicological Sciences. 2016 ; Vol. 153, No. 1. pp. 186-197.
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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.",
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Perfluorooctane sulfonate-choline ion pair formation : A potential mechanism modulating hepatic steatosis and oxidative stress in mice. / Zhang, Limin; Krishnan, Prasad; Ehresman, David J.; Smith, Philip B.; Dutta, Mainak; Bagley, Bradford D.; Chang, Shu Ching; Butenhoff, John L.; Patterson, Andrew David; Peters, Jeffrey Maurice.

In: Toxicological Sciences, Vol. 153, No. 1, kfw120, 01.09.2016, p. 186-197.

Research output: Contribution to journalArticle

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AU - Zhang, Limin

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AU - Dutta, Mainak

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AU - Patterson, Andrew David

AU - Peters, Jeffrey Maurice

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AB - 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.

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