Polychlorinated biphenyl 153 exacerbates nonalcoholic fatty liver disease in C57BL/6 mice.

Polychlorinated biphenyls;Non-alcoholic fatty liver disease;High fat diet;Adipokines;Obesity;PCB 153

Banrida Wahlang, 1986-

University:University of Louisville

Department:Pharmacology and Toxicology

关键词: Polychlorinated biphenyls;    Non-alcoholic fatty liver disease;    High fat diet;    Adipokines;    Obesity;    PCB 153;   

Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=2497&context=etd

美国|英语

来源: The Universite of Louisville's Institutional Repository

【 摘 要 】

Polychlorinated biphenyls (PCBs) are persistent environmental pollutants whichare detectable in the serum of all American adults. Amongst PCB congeners,PCB 153 has the highest serum level. PCBs have been dose-dependentlyassociated with suspected nonalcoholic fatty liver disease (NAFLD), obesity andmetabolic syndrome in epidemiological studies. The purpose of this study is todetermine if PCB 153 induces NAFLD in mice fed a control diet (CD), andexacerbates NAFLD in mice fed a high fat diet (HFD). C57BL6/J mice were fedeither control or 42% milk fat diet for 12 weeks with or without PCB 153 coexposure(50 mg/kg i.p. x 4). Glucose tolerance tests were performed, andplasma/tissues were obtained at necropsy for measurements of adipocytokinelevels, histology, and gene expression microarrays. In mice fed CD, the additionof PCB 153 had little to no effect on any of the measured parameters. In contrast,PCB 153 co-exposure in high fat-fed mice was associated with dramaticallyincreased visceral adiposity, hepatic steatosis and increased plasma adipokines including adiponectin, leptin, resistin and plasminogen activator inhibitor-1 levels.Likewise, co-exposure reduced expression of hepatic genes implicated in ~oxidationwhile increasing the expression of genes associated with lipidbiosynthesis. Regardless of diet, PCB 153 had no effect on insulin resistance ortumor necrosis factor alpha levels. However, HFD+PCB 153 appeared to inducean endoplasmic reticulum (ER) stress response. Therefore, PCB 153 is anobesogen which exacerbates hepatic steatosis; alters adipocytokines; anddisrupts normal hepatic lipid metabolism when administered with HFD. Becauseall U.S. adults have been exposed to PCB 153, this particular nutrient-toxicantinteraction potentially impacts on the progression of human NAFLD.