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2017 Cardiovascular Research Day Abstract Book

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32<br />

PCB 126 Exposure Increases Peripheral Vascular Disease Risk in Mice with Fatty Liver<br />

Jazmyne Barney 1 • Banrida Wahlang, PhD 2 • Brendan Thompson 1 • Chunyan Wang, PhD 3 •<br />

Omer Hamad 3 • Jessie Hoffman, MS 4 • Michael Petriello, PhD 2 • Andrew Morris, PhD 2 •<br />

Bernhard Hennig, PhD 3<br />

1Toxicology and Cancer Biology, University of Kentucky • 2 UK Superfund <strong>Research</strong> Center,<br />

University of Kentucky • 3 Animal and Food Sciences, University of Kentucky • 4 Pharmacology and<br />

Nutritional Sciences, University of Kentucky<br />

Graduate Student<br />

Xenobiotic and energy metabolism is dependent on a functional liver. Exposure to environmental<br />

pollutants like polychlorinated biphenyls (PCBs) is associated with inflammatory diseases,<br />

including non-alcoholic fatty liver disease and atherosclerosis. A compromised liver may play a<br />

critical role in modifying the induction of PCB toxicity and inflammation of the peripheral<br />

vasculature. Over a 14 week study, male C57Bl/6 mice (n=10) were fed an amino acid control diet<br />

or a methionine-choline deficient diet (MCD) with or without oral gavage of PCB 126 (0.5mg/kg).<br />

Post euthanasia, tissue and blood were collected for histological, toxicological, and inflammatory<br />

evaluation. Regardless of diet, PCB 126 induced hepatic steatosis. The MCD+PCB126 group<br />

exhibited fibrosis and increased liver to body weight ratio, suggesting liver injury and toxicity. Mice<br />

fed MCD-diet and exposed to PCB 126 demonstrated altered expression of hepatic genes involved in<br />

carbohydrate and lipid metabolism, indicating metabolic dysfunction. With regard to effects of PCB<br />

126 on extra-hepatic organs, all mice fed MCD diet had decreased expression of plasma leptin and<br />

resistin, and PCB 126 exposed groups appeared to have crown like structures in their epididymal<br />

adipose tissue, indicating the presence of inflammatory cells. In addition, MCD+PCB 126 mice<br />

displayed increased plasma inflammatory markers including Icam-1, Mcp-1, and Tnf-α.<br />

Interestingly, in the MCD+PCB 126 group, plasma ALT and AST levels were increased as well as proatherogenic<br />

trimethylamine-N-oxide (TMAO), implying simultaneous liver damage and increased<br />

peripheral vasculature disease risk. Together these results provide a novel linkage of a<br />

compromised liver to PCB-induced hepatic and vascular inflammation. These finding also a have<br />

translational component, suggesting environmental pollutants can cause inflammatory disease<br />

pathologies by stimulating cross-talk between individual organ systems. (Supported in part by<br />

NIEHS/NIH grant P42ES007380).<br />

48

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