| First Author | Villanueva CJ | Year | 2011 |
| Journal | Cell Metab | Volume | 13 |
| Issue | 4 | Pages | 413-427 |
| PubMed ID | 21459326 | Mgi Jnum | J:172245 |
| Mgi Id | MGI:5005036 | Doi | 10.1016/j.cmet.2011.02.014 |
| Citation | Villanueva CJ, et al. (2011) TLE3 is a dual-function transcriptional coregulator of adipogenesis. Cell Metab 13(4):413-27 |
| abstractText | PPARgamma 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 PPARgamma and Wnt pathways. TLE3 is a direct target of PPARgamma that participates in a feed-forward loop during adipocyte differentiation. TLE3 enhances PPARgamma activity and functions synergistically with PPARgamma 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 beta-catenin in preadipocytes, thereby inhibiting Wnt target gene expression and reversing beta-catenin-dependent repression of adipocyte gene expression. Transgenic expression of TLE3 in adipose tissue in vivo mimics the effects of PPARgamma 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. |
