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The Histone Deacetylase Sirt6 Regulates Glucose Homeostasis via Hif1 alpha
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2010 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 140, no 2, 280-293 p.Article in journal (Refereed) Published
Abstract [en]

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 Hif1 alpha, a critical regulator of nutrient stress responses. Consistent with this notion, SIRT6-deficient cells exhibit increased Hif1 alpha 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.

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2010. Vol. 140, no 2, 280-293 p.
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Natural Sciences
URN: urn:nbn:se:su:diva-48907DOI: 10.1016/j.cell.2009.12.041ISI: 000273826500018OAI: diva2:376360
authorCount :20Available from: 2010-12-10 Created: 2010-12-10 Last updated: 2010-12-10Bibliographically approved

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