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Nuclear Receptor Involvement in PPAA-Induced Metabolic Changes.
Citation:
ROSEN, M. B. Nuclear Receptor Involvement in PPAA-Induced Metabolic Changes. Presented at USEPA-PFAA Days III, Research Triangle Park, NC, June 08 - 10, 2010.
Impact/Purpose:
This talk will consider the potential effects of chronic PFAA exposure on nuclear receptor regulated energy metabolism.
Description:
It has been proposed that certain xenobiotics commonly identified in biomonitoring studies may play a role in the incidence of obesity and metabolic syndrome in the United States and other countries. The list of potential "environmental obesogens" includes endocrine disrupting compounds such as Diethylstillbesterol and Bisphenol A, as well as chemicals that present a variety of toxicities in mammals such as the organotins. Interestingly, perfluoroakyl acids (PFAAs) have also been mentioned as possible environmental obesogens because of their ability to alter energy homeostasis. While it may not be clear how compounds that function as peroxisome proliferator activated receptor alpha (PPARa) ligands could induce obesity, the biological activity of PFAAs is not limited to activation of PPARa. Many of these compounds also activate the constitutive androstane receptor (CAR) and it is now recognized that CAR influences not only xenobiotic metabolism but also certain aspects of energy metabolism as well. Chronic exposure to PPARa agonists also has the potential to alter energy metabolism in ways that are only first beginning to be understood. For example, chemical or metabolic challenge during gestation could result in PPARa-dependent epigenetic modifications which result in persistent alterations in phenotype. This talk will consider the potential effects of chronic PFAA exposure on nuclear receptor regulated energy metabolism. (This abstract does not necessarily reflect EPA policy.)