期刊
EMBO REPORTS
卷 12, 期 10, 页码 1069-1076出版社
WILEY
DOI: 10.1038/embor.2011.151
关键词
SIRT1; CREB; ChREBP; glucagon; nutrient availability
资金
- Ecole Polytechnique Federale de Lausanne (EPFL)
- Swiss National Science Foundation
- EU [ERC-Ideas-Sirtuins-231138]
- National Institutes of Health (NIH/NIDDK) [DK 59820, DK43051, K08DK076726]
- Consejo Nacional de Ciencia y Tecnologia (CONACYT)
- Federation of European Biochemical Societies (FEBS)
- EMBO
- Fondation pour la Recherche Medicale (FRM)
The nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase SIRT1 is a major metabolic regulator activated by energy stresses such as fasting or calorie restriction. SIRT1 activation during fasting not only relies on the increase in the NAD(+)/NADH ratio caused by energy deprivation but also involves an upregulation of SIRT1 mRNA and protein levels in various metabolic tissues. We demonstrate that SIRT1 expression is controlled systemically by the activation of the cyclic AMP response-element-binding protein upon low nutrient availability. Conversely, in the absence of energetic stress, the carbohydrate response-element-binding protein represses the expression of SIRT1. Altogether, these results demonstrate that SIRT1 expression is tightly controlled at the transcriptional level by nutrient availability and further underscore that SIRT1 is a crucial metabolic checkpoint connecting the energetic status with transcriptional programmes.
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