title: SIRT1 Relays Nutritional Inputs to the Circadian Clock Through the Sf1 Neurons of the Ventromedial Hypothalamus.
abstract: Circadian rhythms govern homeostasis and organism physiology. Nutritional cues act as time givers, contributing to the synchronization between central and peripheral clocks. Neuronal food-synchronized clocks are thought to reside in hypothalamic nuclei such as the ventromedial hypothalamus (VMH) and the dorsomedial hypothalamus or extrahypothalamic brain areas such as nucleus accumbens. Interestingly, the metabolic sensor of nicotinamide adenine dinucleotide-dependent deacetylase sirtuin-1 (SIRT1) is highly expressed in the VMH and was shown to contribute to both control of energy balance and clock function. We used mice with targeted ablation of Sirt1 in the steroidogenic factor 1 neurons of the VMH to gain insight on the role played by this deacetylase in the modulation of the central clock by nutritional inputs. By studying circadian behavior and circadian gene expression, we reveal that SIRT1 operates as a metabolic sensor connecting food intake to circadian behavior. Indeed, under food restriction and absence of light, SIRT1 in the VMH contributes to activity behavior and circadian gene expression in the suprachiasmatic nucleus. Thus, under specific physiological conditions, SIRT1 contributes to the modulation of the circadian clock by nutrients.
authors.affiliation: Center for Epigenetics and Metabolism (R.O-S., P.S.-C.), INSERM Unité 904, Department of Biological Chemistry, University of California, Irvine, Irvine, California 92697; and Centre Médical Universitaire/Department Physiology and Metabolism (G.R., R.C.), Université de Genève, 1211 Genève, Switzerland.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Orozco-Solis
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ramadori
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppari
authors.forename: Paolo
authors.initials: P
authors.lastname: Sassone-Corsi
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D057906:Circadian Clocks / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D000072260:RNA Splicing Factors; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014697:Ventromedial Hypothalamic Nucleus / Q000378:metabolism*
chemical_list: D004268:DNA-Binding Proteins; D000072260:RNA Splicing Factors; C491514:Sf1 protein, mouse; D014157:Transcription Factors; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1