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Biochem Pharmacol. 2009 Nov 15;78(10):1323-9. doi: 10.1016/j.bcp.2009.07.001. Epub 2009 Jul 8.

Augmentation of PPARgamma-TAZ interaction contributes to the anti-adipogenic activity of KR62980.

Author information

1
College of Pharmacy and Division of Life and Pharmaceutical Sciences and Center for Cell Signaling & Drug Discovery Research, Ewha Womans University, 11-1 Daehyun-Dong, Sudaemun-Ku, Seoul 120-750, Republic of Korea. jh_hong@korea.ac.kr

Abstract

Peroxisome proliferator-activated receptor gamma (PPARgamma) is a ligand-activated transcription factor that plays a pivotal role in the modulation of gene expression involved in adipocyte differentiation and insulin sensitivity. It has been previously established that thiazolidinedione (TZD) PPARgamma ligands such as rosiglitazone have potent anti-diabetic and adipogenic activities. A novel non-TZD ligand for PPARgamma, KR62980 has recently been characterized to increase insulin sensitivity and to be weakly adipogenic in 3T3-L1 cells or anti-adipogenic in rosiglitazone-induced adipocyte differentiation. In this study, we have confirmed that KR62980 substantially suppresses rosiglitazone-induced adipocyte differentiation and attenuates adipogenic gene expression via an induced reduction in PPARgamma activity. KR62980 increased the nuclear localization of TAZ, a PPARgamma suppressor, and also enhanced the interaction between PPARgamma and TAZ, thus resulting in the TAZ-mediated suppression of PPARgamma activity. Furthermore, KR62980 failed to suppress PPARgamma-mediated adipogenic gene expression and adipocyte differentiation in TAZ knockdown 3T3-L1 cells, thus indicating a TAZ-dependent suppressive activity of KR62980 on PPARgamma-mediated function. These findings strongly suggest that the novel PPARgamma ligand, KR62980, may prove to be beneficial to anti-adipogenic function through the suppression of PPARgamma-mediated adipocyte differentiation by activating TAZ.

PMID:
19591806
DOI:
10.1016/j.bcp.2009.07.001
[Indexed for MEDLINE]

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