A synthetic antagonist for the peroxisome proliferator-activated receptor γ inhibits adipocyte differentiation

Abstract

While searching for natural ligands for the peroxisome proliferator- activated receptor (PPAR) γ, we identified a synthetic compound that binds to this receptor, Bisphenol A diglycidyl ether (BADGE) is a ligand for PPARγ with a K(d(app)) of 100 μM. This compound has no apparent ability to activate the transcriptional activity of PPARγ, however, BADGE can antagonize the ability of agonist ligands such as rosiglitazone to activate the transcriptional and adipogenic action of this receptor. BADGE also specifically blocks the ability of natural adipogenic cell lines such as 3T3- L1 and 3T3-F442A cells to undergo hormone-mediated cell differentiation. These results provide the first pharmacological evidence that PPARγ activity is required for the hormonally induced differentiation of adipogenic cells.