A peroxisome proliferator-activated receptor γ (PPARγ)/ PPARγ coactivator 1β autoregulatory loop in adipocyte mitochondrial function

Tuo Deng, Douglas H. Sieglaff, Aijun Zhang, Christopher J. Lyon, Steven D. Ayers, Aleksandra Cvoro, Anisha A. Gupte, Xuefeng Xia, John D. Baxter, Paul Webb, Willa A. Hsueh

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Peroxisome proliferator-activated receptor γ (PPARγ) activation induces adipogenesis and also enhances lipogenesis, mitochondrial activity, and insulin sensitivity in adipocytes. Whereas some studies implicate PPARγ coactivator 1α (PGC-1α) in the mitochondrial effect, the mechanisms involved in PPARγ regulation of adipocyte mitochondrial function are not resolved. PPARγ-activating ligands (thiazolidinediones (TZDs)) are important insulin sensitizers and were recently shown to indirectly induce PGC-1β transcription in osteoclasts. Here, we asked whether similar effects occur in adipocytes and show that TZDs also strongly induce PGC-1β in cultured 3T3-L1 cells. This effect, however, differs from the indirect effect proposed for bone and is rapid and direct and involves PPARγ interactions with an intronic PPARγ response element cluster in the PGC-1β locus. TZD treatment of cultured adipocytes results in up-regulation of mitochondrial marker genes, and increased mitochondrial activity and use of short interfering RNA confirms that these effects require PGC-1β. PGC-1β did not participate in PPARγ effects on adipogenesis or lipogenesis, and PGC-1α knockdown did not alter insulin-responsive glucose uptake into 3T3-L1 cells. Similar effects on PGC-1β and mitochondrial gene expression are seen in vivo; fractionation of obese mouse adipose tissue reveals that PPARγ and PGC-1β, but not PGC-1α, are coordinately up-regulated in adipocytes relative to preadipocytes and that TZD treatment induces PGC-1β and mitochondrial marker genes in adipose tissue of obese mice. We propose that PPARγ directly induces PGC-1β expression in adipocytes and that this effect regulates adipocyte mitochondrial activity.

Original languageEnglish (US)
Pages (from-to)30723-30731
Number of pages9
JournalJournal of Biological Chemistry
Volume286
Issue number35
DOIs
StatePublished - Sep 2 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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