| First Author | Yao L | Year | 2017 |
| Journal | Cell Rep | Volume | 20 |
| Issue | 3 | Pages | 641-654 |
| PubMed ID | 28723567 | Mgi Jnum | J:249895 |
| Mgi Id | MGI:6101021 | Doi | 10.1016/j.celrep.2017.06.069 |
| Citation | Yao L, et al. (2017) Cold-Inducible SIRT6 Regulates Thermogenesis of Brown and Beige Fat. Cell Rep 20(3):641-654 |
| abstractText | Promoting development and function of brown and beige fat may reduce obesity. Here, we show that fat SIRT6 expression is markedly induced by cold exposure and a beta-adrenergic agonist. Deletion of SIRT6 in adipose tissue impairs the thermogenic function of brown adipocytes, causing a morphological "whitening" of brown fat, reduced oxygen (O2) consumption, obesity, decreased core body temperature, and cold sensitivity. Fat SIRT6-deleted mice exhibit increased blood glucose levels, severe insulin resistance, and hepatic steatosis. Moreover, SIRT6 deficiency inhibits the browning of white adipose tissue (WAT) following cold exposure or beta3-agonist treatment. Depletion of SIRT6 expression in brown adipocytes reduces expression of thermogenic genes, causing a reduction in cellular respiration. Conversely, SIRT6 overexpression in primary fat cells stimulates the thermogenic program. Mechanistically, SIRT6 interacts with and promotes phospho-ATF2 binding to the PGC-1alpha gene promoter to activate its expression. The present study reveals a critical role for SIRT6 in regulating thermogenesis of fat. |
