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TLE3 is a dual-function transcriptional coregulator of adipogenesis.

PPARγ and Wnt signaling are central positive and negative regulators of adipogenesis, respectively. Here we identify the groucho family member TLE3 as a transcriptional integrator of the PPARγ and Wnt pathways. TLE3 is a direct target of PPARγ that participates in a feed-forward loop during adipocyte differentiation. TLE3 enhances PPARγ activity and functions synergistically with PPARγ on its target promoters to stimulate adipogenesis. At the same time, induction of TLE3 during differentiation provides a mechanism for termination of Wnt signaling. TLE3 antagonizes TCF4 activation by β-catenin in preadipocytes, thereby inhibiting Wnt target gene expression and reversing β-catenin-dependent repression of adipocyte gene expression. Transgenic expression of TLE3 in adipose tissue in vivo mimics the effects of PPARγ agonist and ameliorates high-fat-diet-induced insulin resistance. Our data suggest that TLE3 acts as a dual-function switch, driving the formation of both active and repressive transcriptional complexes that facilitate the adipogenic program.

Pubmed ID: 21459326


  • Villanueva CJ
  • Waki H
  • Godio C
  • Nielsen R
  • Chou WL
  • Vargas L
  • Wroblewski K
  • Schmedt C
  • Chao LC
  • Boyadjian R
  • Mandrup S
  • Hevener A
  • Saez E
  • Tontonoz P


Cell metabolism

Publication Data

April 6, 2011

Associated Grants

  • Agency: NIDDK NIH HHS, Id: DK063491
  • Agency: NIDDK NIH HHS, Id: DK081003
  • Agency: NHLBI NIH HHS, Id: HL069766
  • Agency: NHLBI NIH HHS, Id: HL090553
  • Agency: NHLBI NIH HHS, Id: P01 HL090553
  • Agency: NIDDK NIH HHS, Id: R01 DK081003
  • Agency: NIDDK NIH HHS, Id: R01 DK089109
  • Agency: Howard Hughes Medical Institute, Id:

Mesh Terms

  • Adipocytes
  • Adipogenesis
  • Animals
  • Basic Helix-Loop-Helix Leucine Zipper Transcription Factors
  • Cell Line
  • Co-Repressor Proteins
  • Dietary Fats
  • Gene Expression Regulation
  • Insulin Resistance
  • Mice
  • PPAR gamma
  • Proteins
  • RNA Interference
  • RNA, Small Interfering
  • Signal Transduction
  • Transcription, Genetic
  • Wnt Proteins
  • beta Catenin