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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Evaluation of Aroclor 1260 exposure in a mouse model of diet-induced obesity and non-alcoholic fatty liver disease.

Authors: Wahlang, Banrida; Song, Ming; Beier, Juliane I; Cameron Falkner, K; Al-Eryani, Laila; Clair, Heather B; Prough, Russell A; Osborne, Tanasa S; Malarkey, David E; States, J Christopher; Cave, Matthew C

Published In Toxicol Appl Pharmacol, (2014 Sep 15)

Abstract: Polychlorinated biphenyls (PCBs) are persistent organic pollutants associated with non-alcoholic fatty liver disease (NAFLD) in epidemiologic studies. The purpose of this study was to evaluate the hepatic effects of a PCB mixture, Aroclor 1260, whose composition mimics human bioaccumulation patterns, in a mouse model of diet-induced obesity (DIO). Male C57Bl/6J mice were fed control diet or 42% high fat diet (HFD) and exposed to Aroclor 1260 (20mg/kg or 200mg/kg in corn oil) for 12weeks. A glucose tolerance test was performed; plasma/tissues were obtained at necropsy for measurements of adipocytokine levels, histology, and gene expression. Aroclor 1260 exposure was associated with decreased body fat in HFD-fed mice but had no effect on blood glucose/lipid levels. Paradoxically, Aroclor 1260+HFD co-exposed mice demonstrated increased hepatic inflammatory foci at both doses while the degree of steatosis did not change. Serum cytokines, ALT levels and hepatic expression of IL-6 and TNFα were increased only at 20mg/kg, suggesting an inhibition of pro-inflammatory cytokine production at the 200mg/kg exposure. Aroclor 1260 induced hepatic expression of cytochrome P450s including Cyp3a11 (Pregnane-Xenobiotic Receptor target) and Cyp2b10 (constitutive androstane receptor target) but Cyp2b10 inducibility was diminished with HFD-feeding. Cyp1a2 (aryl hydrocarbon Receptor target) was induced only at 200mg/kg. In summary, Aroclor 1260 worsened hepatic and systemic inflammation in DIO. The results indicated a bimodal response of PCB-diet interactions in the context of inflammation which could potentially be explained by xenobiotic receptor activation. Thus, PCB exposure may be a relevant "second hit" in the transformation of steatosis to steatohepatitis.

PubMed ID: 24998970 Exiting the NIEHS site

MeSH Terms: Adipokines/metabolism; Adipose Tissue/pathology; Animals; Aroclors/toxicity*; Aryl Hydrocarbon Hydroxylases/biosynthesis; Aryl Hydrocarbon Hydroxylases/genetics; Blood Glucose/metabolism; Cholesterol/metabolism; Cytochrome P-450 CYP3A/biosynthesis; Cytochrome P-450 CYP3A/genetics; Cytochrome P450 Family 2; Diet; Environmental Pollutants/toxicity*; Fatty Liver/chemically induced*; Fatty Liver/pathology; Gene Expression/drug effects; Glucose Tolerance Test; Inflammation/chemically induced; Inflammation/pathology; Liver/pathology; Membrane Proteins/biosynthesis; Membrane Proteins/genetics; Mice; Mice, Inbred C57BL; Non-alcoholic Fatty Liver Disease; Obesity/chemically induced*; Obesity/pathology; Real-Time Polymerase Chain Reaction; Receptors, Aryl Hydrocarbon/biosynthesis; Receptors, Aryl Hydrocarbon/genetics; Steroid Hydroxylases/biosynthesis; Steroid Hydroxylases/genetics; Toll-Like Receptor 4/biosynthesis; Toll-Like Receptor 4/genetics; Triglycerides/metabolism

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