A Novel PPAR gamma Agonist, SP1818, Shows Different Coactivator Profile with Rosiglitazone

Abstract

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a ligand-activated transcription factor that is used as a target for anti-diabetic drug development. In a search for novel PPAR gamma agonists, the beta-carboxyethyl-rhodanine derivative SP1818 was identified. We report here the characteristics of SP1818 as a selective PPAR gamma agonist. In transactivation assays, SP1818 selectively activated PPAR gamma, but the degree of PPAR gamma stimulation was less than with 1 mu M rosiglitazone. SP1818 also stimulated glucose uptake in a concentration-dependent manner. The adipocyte differentiation markers adiponectin, scavenger receptor CD36 and aP2 were weakly induced by treatment with SP1818, and TRAP220 subunit was specifically recruited into PPAR gamma activated by rosiglitazone but not PPAR gamma activated by SP1818.