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The histone deacetylase Sirt6 regulates glucose homeostasis via Hif1alpha.
| Publication Type | Journal Article |
| Authors | Clish, CB, Iliopoulos O., and Weissleder R. |
| Abstract | 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. |
| Year of Publication | 2010 |
| Journal | Cell |
| Volume | 140 |
| Issue | 2 |
| Pages | 280-93 |
| Date Published (YYYY/MM/DD) | 2010/01/22 |
| ISSN Number | 0092-8674 |
| DOI | 10.1016/j.cell.2009.12.041 |
| PubMed | http://www.ncbi.nlm.nih.gov/pubmed/20141841?dopt=Abstract |




