| First Author | Li P | Year | 2011 |
| Journal | Cell | Volume | 147 |
| Issue | 4 | Pages | 815-26 |
| PubMed ID | 22078880 | Mgi Jnum | J:178828 |
| Mgi Id | MGI:5300394 | Doi | 10.1016/j.cell.2011.09.050 |
| Citation | Li P, et al. (2011) Adipocyte NCoR knockout decreases PPARgamma phosphorylation and enhances PPARgamma activity and insulin sensitivity. Cell 147(4):815-26 |
| abstractText | Insulin resistance, tissue inflammation, and adipose tissue dysfunction are features of obesity and Type 2 diabetes. We generated adipocyte-specific Nuclear Receptor Corepressor (NCoR) knockout (AKO) mice to investigate the function of NCoR in adipocyte biology, glucose and insulin homeostasis. Despite increased obesity, glucose tolerance was improved in AKO mice, and clamp studies demonstrated enhanced insulin sensitivity in liver, muscle, and fat. Adipose tissue macrophage infiltration and inflammation were also decreased. PPARgamma response genes were upregulated in adipose tissue from AKO mice and CDK5-mediated PPARgamma ser-273 phosphorylation was reduced, creating a constitutively active PPARgamma state. This identifies NCoR as an adaptor protein that enhances the ability of CDK5 to associate with and phosphorylate PPARgamma. The dominant function of adipocyte NCoR is to transrepress PPARgamma and promote PPARgamma ser-273 phosphorylation, such that NCoR deletion leads to adipogenesis, reduced inflammation, and enhanced systemic insulin sensitivity, phenocopying the TZD-treated state. |
