| First Author | El Ouarrat D | Year | 2020 |
| Journal | Cell Metab | Volume | 31 |
| Issue | 1 | Pages | 162-173.e5 |
| PubMed ID | 31708444 | Mgi Jnum | J:286185 |
| Mgi Id | MGI:6400630 | Doi | 10.1016/j.cmet.2019.10.003 |
| Citation | El Ouarrat D, et al. (2020) TAZ Is a Negative Regulator of PPARgamma Activity in Adipocytes and TAZ Deletion Improves Insulin Sensitivity and Glucose Tolerance. Cell Metab 31(1):162-173.e5 |
| abstractText | Insulin resistance is a major factor in obesity-linked type 2 diabetes. PPARgamma is a master regulator of adipogenesis, and small molecule agonists, termed thiazolidinediones, are potent therapeutic insulin sensitizers. Here, we studied the role of transcriptional co-activator with PDZ-binding motif (TAZ) as a transcriptional co-repressor of PPARgamma. We found that adipocyte-specific TAZ knockout (TAZ AKO) mice demonstrate a constitutively active PPARgamma state. Obese TAZ AKO mice show improved glucose tolerance and insulin sensitivity compared to littermate controls. PPARgamma response genes are upregulated in adipose tissue from TAZ AKO mice and adipose tissue inflammation was also decreased. In vitro and in vivo mechanistic studies revealed that the TAZ-PPARgamma interaction is partially dependent on ERK-mediated Ser112 PPARgamma phosphorylation. As adipocyte PPARgamma Ser112 phosphorylation is increased in obesity, repression of PPARgamma activity by TAZ could contribute to insulin resistance. These results identify TAZ as a new factor in the development of obesity-induced insulin resistance. |
