| First Author | Zhong L | Year | 2010 |
| Journal | Cell | Volume | 140 |
| Issue | 2 | Pages | 280-93 |
| PubMed ID | 20141841 | Mgi Jnum | J:167957 |
| Mgi Id | MGI:4881401 | Doi | 10.1016/j.cell.2009.12.041 |
| Citation | Zhong L, et al. (2010) The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha. Cell 140(2):280-93 |
| abstractText | SIRT6 is a member of a highly conserved family of NAD(+)-dependent deacetylases with various roles in metabolism, stress resistance, and life span. SIRT6-deficient mice develop normally but succumb to a lethal hypoglycemia early in life; however, the mechanism underlying this hypoglycemia remained unclear. Here, we demonstrate that SIRT6 functions as a histone H3K9 deacetylase to control the expression of multiple glycolytic genes. Specifically, SIRT6 appears to function as a corepressor of the transcription factor Hif1alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1alpha activity and show increased glucose uptake with upregulation of glycolysis and diminished mitochondrial respiration. Our studies uncover a role for the chromatin factor SIRT6 as a master regulator of glucose homeostasis and may provide the basis for novel therapeutic approaches against metabolic diseases, such as diabetes and obesity. |
