学位论文详细信息
PCB-associated steatohepatitis and the role of nuclear receptors.
steatohepatitis;polychlorinated biphenyls;metabolism-disrupting chemicals;Anniston, Alabama;non-alcoholic fatty liver disease
Heather Brooke Clair
University:University of Louisville
Department:Biochemistry and Molecular Biology
关键词: steatohepatitis;    polychlorinated biphenyls;    metabolism-disrupting chemicals;    Anniston, Alabama;    non-alcoholic fatty liver disease;   
Others  :  https://ir.library.louisville.edu/cgi/viewcontent.cgi?article=3959&context=etd
美国|英语
来源: The Universite of Louisville's Institutional Repository
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【 摘 要 】

Metabolic diseases, including fatty liver disease, hyperglycemia, and obesity, result when body systems responsible for managing allostasis (dynamic homeostasis across systems) are pressured beyond their collective compensatory reserve. Nutritional excess contributes to this state, the capacity of which is limited by genetic variation, and failure of one system will gradually lead to pathological overload in the others. Agents which act directly on the communication machinery linking these connected systems can also change the point at which allostatic load becomes allostatic overload. Environmental exposure to polychlorinated biphenyls (PCBs), a class of persistent organic pollutant, is associated with a specific form of toxicant-associated steatohepatitis, fatty liver disease with inflammatory infiltration. PCBs are known to be ligands for the xenobiotic receptors, which, when activated, modulate the transcription of both xenobiotic and intermediary metabolic targets. We investigated the prevalence and characteristics of liver disease in a human population with high environmental PCB exposure, transcriptional changes in the liver in a mouse model of PCB/high-fat diet coexposure, and transcriptional changes attributable to xenobiotic receptors in a primary hepatocyte model.

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