TCDD mediated inhibition of PPAR-gamma expression

University Of Wisconsin Madison, Madison WI

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Abstract

[unreadable] DESCRIPTION (provided by applicant): This lab is studying AhR signaling within C3H10T1/2 mouse embryo fibroblasts, a multipotential cell line that can differentiate into tat cells under the appropriate conditions. Adipogenesis can be inhibited by pretreatment Aryl-hydrocarbon receptor (AhR) ligand TCDD. We note a strong correlation between Peroxisome Proliferator-Activated Receptor gamma (PPAR-gamma) expression at 48hrs with the number of mature adipocytes at day 8. We hypothesize that AhR signaling mediates its block on adipogenesis by affecting PPAR-gamma expression, specifically at the PPARg promoter. This research will identify what elements in the PPAR-gamma promoter are necessary for PPAR-gamma expression and for the TCDD block. This work has also shown that the TCDD block can be reversed if either of the MEK inhibitors PD98059 and UO128 is concurrently given with the hormonal differentiation mixture. Thus, within a certain time frame, the TCDD block on PPAR-ganima has an ERK-sensitive component. This research will investigate the signaling between the ERK-sensitive pathway and the AhR pathway. The overall goal is to better characterize the means by which TCDD blocks the adipocytes differentiation process.