5-(3,5-Di-tert-butyl-4-hydroxybenzylidene) thiazolidine-2,4-dione modulates peroxisome proliferators-activated receptor γ in 3T3-L1 adipocytes:: Roles as a PPARγ ligand

Based on the binding between peroxisome proliferators-activated receptor gamma (PPAR-gamma) and steroid receptor co-activator-1 (SRC-1), an enzyme-linked immunosorbent assay (ELISA) was used to screen new PPAR-gamma ligands from various benzylidinethiazole derivatives, which have anti-inflammatory activity. Among those derivatives, 5-(3,5-di-tert-butyl-4-hydroxybenzylidene) thiazolidine-2,4-dione (BTZD) increased the binding between PPAR-gamma and SRC-1. BTZD was found to induce adipogenesis and PPAR-gamma trans-activation in 3T3-L1 pre-adipocyte, and increased the binding between PPAR-gamma and SRC-1 in in vitro binding assay and complex consisting of PPAR-gamma and SRC-1 in the co-immunoprecipitaion. Chromatin immunoprecipitation (ChIP) analysis revealed that BTZD induced the binding of PPAR-gamma-SRC-1 complex to PPAR response element (PPRE) in the same pattern of other PPAR-gamma ligand. From these studies, we have identified and studied the function of a new PPAR-gamma ligand, BTZD. We suggest that BTZD can be used as a modulator of PPAR-gamma. This study applying ELISA and ChIP assay can offer new methods to screen PPAR gamma ligand and understand the effects of PPAR-gamma ligands on inflammation. (c) 2005 Elsevier Ireland Ltd. All rights reserved.