title: CREB and ChREBP oppositely regulate SIRT1 expression in response to energy availability.
abstract: 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.
authors.affiliation: Ecole Polytechnique Fédérale de Lausanne, Laboratory of Integrative and Systems Physiology and Nestlé Chair in Energy Metabolism, 1015 Lausanne, Switzerland.
authors.forename: Lilia G
authors.initials: LG
authors.lastname: Noriega
authors.forename: Jérôme N
authors.initials: JN
authors.lastname: Feige
authors.forename: Carles
authors.initials: C
authors.lastname: Canto
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Jiujiu
authors.initials: J
authors.lastname: Yu
authors.forename: Mark A
authors.initials: MA
authors.lastname: Herman
authors.forename: Chikage
authors.initials: C
authors.lastname: Mataki
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Kahn
authors.forename: Johan
authors.initials: J
authors.lastname: Auwerx
mesh_terms: D000818:Animals; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D016466:CHO Cells; D045744:Cell Line, Tumor; D006224:Cricetinae; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D005215:Fasting; D005786:Gene Expression Regulation; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009687:Nuclear Proteins / Q000378:metabolism*; D056564:Sirtuin 1 / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D017362:Cyclic AMP Response Element-Binding Protein; C506001:Mlxipl protein, mouse; D009687:Nuclear Proteins; D014157:Transcription Factors; D056564:Sirtuin 1