Peroxisome Proliferator-activated Receptor (PPAR)-2 controls adipocyte differentiation and adipose tissue function through the regulation of the activity of the retinoid X receptor/PPARγ heterodimer

Péter Bai, Sander M. Houten, Aline Huber, Valérie Schreiber, Mitsuhiro Watanabe, Borbála Kiss, Gilbert De Murcia, Johan Auwerx, Josiane Ménissier-De Murcia

Research output: Contribution to journalArticlepeer-review

77 Citations (Scopus)

Abstract

The peroxisome proliferator-activated receptor-γ (PPARγ, NR1C3) in complex with the retinoid X receptor (RXR) plays a central role in white adipose tissue (WAT) differentiation and function, regulating the expression of key WAT proteins. In this report we show that poly(ADP-ribose) polymerase-2 (PARP-2), also known as an enzyme participating in the surveillance of the genome integrity, is a member of the PPARγ/RXR transcription machinery. PARP-2-/- mice accumulate less WAT, characterized by smaller adipocytes. In the WAT of PARP-2-/- mice the expression of a number of PPARγ target genes is reduced despite the fact that PPARγ1 and -γ2 are expressed at normal levels. Consistent with this, PARP-2 -/- mouse embryonic fibroblasts fail to differentiate to adipocytes. In transient transfection assays, PARP-2 small interference RNA decreases basal activity and ligand-dependent activation of PPARγ, whereas PARP-2 overexpression enhances the basal activity of PPARγ, although it does not change the maximal ligand-dependent activation. In addition, we show a DNA-dependent interaction of PARP-2 and PPARγ/RXR heterodimer by chromatin immunoprecipitation. In combination, our results suggest that PARP-2 is a novel cofactor of PPARγ activity.

Original languageEnglish
Pages (from-to)37738-37746
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number52
DOIs
Publication statusPublished - 2007 Dec 28
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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