Journal
JOURNAL OF NUTRITIONAL BIOCHEMISTRY
Volume 24, Issue 9, Pages 1587-1595Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.jnutbio.2013.01.009
Keywords
NAFLD; PCB; PCBs; TASH; POPs
Funding
- University of Louisville Diabetes and Obesity Center
- Alcohol Research Center
- Center for Environmental Genomics and Integrative Biology
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Background: Polychlorinated biphenyls (PCBs) are persistent environmental pollutants that are detectable in the serum of all American adults. Amongst PCB congeners, PCB 153 has the highest serum level. PCBs have been dose-dependently associated with obesity, metabolic syndrome and nonalcoholic fatty liver disease (NAFLD) in epidemiological studies. Objective: The purpose of this study is to determine mechanisms by which PCB 153 worsens diet-induced obesity and NAFLD in male mice fed a high-fat diet (HFD). Methods: Male C57BL6/J mice were fed either control or 42% milk fat diet for 12 weeks with or without PCB 153 coexposure (50 mg/kg ip x 4). Glucose tolerance test was performed, and plasma and tissues were obtained at necropsy for measurements of adipocytokine levels, histology and gene expression. Results: In control diet-fed mice, addition of PCB 153 had minimal effects on any of the measured parameters. However, PCB 153 treatment in high-fat-fed mice was associated with increased visceral adiposity, hepatic steatosis and plasma adipokines including adiponectin, leptin, resistin and plasminogen activator inhibitor-1 levels. Likewise, coexposure reduced expression of hepatic genes implicated in beta-oxidation while increasing the expression of genes associated with lipid biosynthesis. Regardless of diet, PCB 153 had no effect on insulin resistance or tumor necrosis factor alpha levels. Conclusion: PCB 153 is an obesogen that exacerbates hepatic steatosis, alters adipocytokines and disrupts normal hepatic lipid metabolism when administered with HFD but not control diet. Because all US adults have been exposed to PCB 153, this particular nutrient-toxicant interaction potentially impacts human obesity/NAFLD. (C) 2013 Elsevier Inc. All rights reserved.
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