TLE3 Is a Dual-Function Transcriptional Coregulator of Adipogenesis

Claudio J Villanueva, Hironori Waki, Cristina Godio, Ronni Nielsen, Wen-Ling Chou, Leo Vargas, Kevin Wroblewski, Christian Schmedt, Lily C Chao, Rima Boyadjian, Susanne Mandrup, Andrea Hevener, Enrique Saez, Peter Tontonoz

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Resumé

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.
OriginalsprogEngelsk
TidsskriftCell Metabolism
Vol/bind13
Udgave nummer4
Sider (fra-til)413-27
Antal sider15
ISSN1550-4131
DOI
StatusUdgivet - 6. apr. 2011

Fingeraftryk

Adipogenesis
Adipocytes
Wnt Signaling Pathway
High Fat Diet
Insulin Resistance
Adipose Tissue

Citer dette

Villanueva, C. J., Waki, H., Godio, C., Nielsen, R., Chou, W-L., Vargas, L., ... Tontonoz, P. (2011). TLE3 Is a Dual-Function Transcriptional Coregulator of Adipogenesis. Cell Metabolism, 13(4), 413-27. https://doi.org/10.1016/j.cmet.2011.02.014
Villanueva, Claudio J ; Waki, Hironori ; Godio, Cristina ; Nielsen, Ronni ; Chou, Wen-Ling ; Vargas, Leo ; Wroblewski, Kevin ; Schmedt, Christian ; Chao, Lily C ; Boyadjian, Rima ; Mandrup, Susanne ; Hevener, Andrea ; Saez, Enrique ; Tontonoz, Peter. / TLE3 Is a Dual-Function Transcriptional Coregulator of Adipogenesis. I: Cell Metabolism. 2011 ; Bind 13, Nr. 4. s. 413-27.
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abstract = "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.",
author = "Villanueva, {Claudio J} and Hironori Waki and Cristina Godio and Ronni Nielsen and Wen-Ling Chou and Leo Vargas and Kevin Wroblewski and Christian Schmedt and Chao, {Lily C} and Rima Boyadjian and Susanne Mandrup and Andrea Hevener and Enrique Saez and Peter Tontonoz",
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Villanueva, CJ, Waki, H, Godio, C, Nielsen, R, Chou, W-L, Vargas, L, Wroblewski, K, Schmedt, C, Chao, LC, Boyadjian, R, Mandrup, S, Hevener, A, Saez, E & Tontonoz, P 2011, 'TLE3 Is a Dual-Function Transcriptional Coregulator of Adipogenesis', Cell Metabolism, bind 13, nr. 4, s. 413-27. https://doi.org/10.1016/j.cmet.2011.02.014

TLE3 Is a Dual-Function Transcriptional Coregulator of Adipogenesis. / Villanueva, Claudio J; Waki, Hironori; Godio, Cristina; Nielsen, Ronni; Chou, Wen-Ling; Vargas, Leo; Wroblewski, Kevin; Schmedt, Christian; Chao, Lily C; Boyadjian, Rima; Mandrup, Susanne; Hevener, Andrea; Saez, Enrique; Tontonoz, Peter.

I: Cell Metabolism, Bind 13, Nr. 4, 06.04.2011, s. 413-27.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - TLE3 Is a Dual-Function Transcriptional Coregulator of Adipogenesis

AU - Villanueva, Claudio J

AU - Waki, Hironori

AU - Godio, Cristina

AU - Nielsen, Ronni

AU - Chou, Wen-Ling

AU - Vargas, Leo

AU - Wroblewski, Kevin

AU - Schmedt, Christian

AU - Chao, Lily C

AU - Boyadjian, Rima

AU - Mandrup, Susanne

AU - Hevener, Andrea

AU - Saez, Enrique

AU - Tontonoz, Peter

N1 - Copyright © 2011 Elsevier Inc. All rights reserved.

PY - 2011/4/6

Y1 - 2011/4/6

N2 - 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.

AB - 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.

U2 - 10.1016/j.cmet.2011.02.014

DO - 10.1016/j.cmet.2011.02.014

M3 - Journal article

C2 - 21459326

VL - 13

SP - 413

EP - 427

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 4

ER -