| First Author | Qiang L | Year | 2012 |
| Journal | Cell | Volume | 150 |
| Issue | 3 | Pages | 620-32 |
| PubMed ID | 22863012 | Mgi Jnum | J:187882 |
| Mgi Id | MGI:5438686 | Doi | 10.1016/j.cell.2012.06.027 |
| Citation | Qiang L, et al. (2012) Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppargamma. Cell 150(3):620-32 |
| abstractText | Brown adipose tissue (BAT) can disperse stored energy as heat. Promoting BAT-like features in white adipose (WAT) is an attractive, if elusive, therapeutic approach to staunch the current obesity epidemic. Here we report that gain of function of the NAD-dependent deacetylase SirT1 or loss of function of its endogenous inhibitor Deleted in breast cancer-1 (Dbc1) promote "browning" of WAT by deacetylating peroxisome proliferator-activated receptor (Ppar)-gamma on Lys268 and Lys293. SirT1-dependent deacetylation of Lys268 and Lys293 is required to recruit the BAT program coactivator Prdm16 to Ppargamma, leading to selective induction of BAT genes and repression of visceral WAT genes associated with insulin resistance. An acetylation-defective Ppargamma mutant induces a brown phenotype in white adipocytes, whereas an acetylated mimetic fails to induce "brown" genes but retains the ability to activate "white" genes. We propose that SirT1-dependent Ppargamma deacetylation is a form of selective Ppargamma modulation of potential therapeutic import. |
