CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability

Lilia G. Noriega, Jérôme N. Feige, Carles Canto, Hiroyasu Yamamoto, Jiujiu Yu, Mark A. Herman, Chikage Mataki, Barbara B. Kahn, Johan Auwerx

Research output: Contribution to journalArticlepeer-review

135 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1069-1076
Number of pages8
JournalEMBO Reports
Issue number10
StatePublished - Oct 2011
Externally publishedYes


  • CREB
  • ChREBP
  • SIRT1
  • glucagon
  • nutrient availability

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Genetics


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