Polychlorinated biphenyl 153 is a diet-dependent obesogen that worsens nonalcoholic fatty liver disease in male C57BL6/J mice

被引:149
作者
Wahlang, Banrida [1 ]
Falkner, K. Cameron [2 ,5 ]
Gregory, Bonnie [2 ]
Ansert, Douglas [3 ,4 ]
Young, David [3 ,4 ,5 ]
Conklin, Daniel J. [1 ,3 ,4 ,5 ]
Bhatnagar, Aruni [1 ,3 ,4 ,5 ,6 ]
McClain, Craig J. [1 ,2 ,5 ,7 ]
Cave, Matt [1 ,2 ,5 ,7 ]
机构
[1] Univ Louisville, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA
[2] Univ Louisville, Dept Med, Div Gastroenterol Hepatol & Nutr, Louisville, KY 40292 USA
[3] Univ Louisville, Dept Med, Div Cardiovasc Med, Louisville, KY 40292 USA
[4] Univ Louisville, Inst Mol Cardiol, Louisville, KY 40292 USA
[5] Univ Louisville, Diabet & Obes Ctr, Louisville, KY 40292 USA
[6] Univ Louisville, Dept Biochem & Mol Biol, Louisville, KY 40292 USA
[7] Robley Rex Vet Affairs Med Ctr, Louisville, KY USA
关键词
NAFLD; PCB; PCBs; TASH; POPs; PERSISTENT ORGANIC POLLUTANTS; SERUM CONCENTRATIONS; GENE-EXPRESSION; NATIONAL-HEALTH; STEATOHEPATITIS; PREVALENCE; METABOLISM; NUTRITION; RECEPTOR; ADULTS;
D O I
10.1016/j.jnutbio.2013.01.009
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:1587 / 1595
页数:9
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