title: Brain SIRT1: anatomical distribution and regulation by energy availability.
abstract: SIRT1 is a nicotinamide adenosine dinucleotide-dependent deacetylase that orchestrates key metabolic adaptations to nutrient deprivation in peripheral tissues. SIRT1 is induced also in the brain by reduced energy intake. However, very little is known about SIRT1 distribution and the biochemical phenotypes of SIRT1-expressing cells in the neuraxis. Unknown are also the brain sites in which SIRT1 is regulated by energy availability and whether these regulations are altered in a genetic model of obesity. To address these issues, we performed in situ hybridization histochemistry analyses and found that Sirt1 mRNA is highly expressed in metabolically relevant sites. These include, but are not limited to, the hypothalamic arcuate, ventromedial, dorsomedial, and paraventricular nuclei and the area postrema and the nucleus of the solitary tract in the hindbrain. Of note, our single-cell reverse transcription-PCR analyses revealed that Sirt1 mRNA is expressed in pro-opiomelanocortin neurons that are critical for normal body weight and glucose homeostasis. We also found that SIRT1 protein levels are restrictedly increased in the hypothalamus in the fasted brain. Of note, we found that this hypothalamic-specific, fasting-induced SIRT1 regulation is altered in leptin-deficient, obese mice. Collectively, our findings establish the distribution of Sirt1 mRNA throughout the neuraxis and suggest a previously unrecognized role of brain SIRT1 in regulating energy homeostasis.
authors.affiliation: Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9077, USA.
authors.forename: Giorgio
authors.initials: G
authors.lastname: Ramadori
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Lee
authors.forename: Angie L
authors.initials: AL
authors.lastname: Bookout
authors.forename: Syann
authors.initials: S
authors.lastname: Lee
authors.forename: Kevin W
authors.initials: KW
authors.lastname: Williams
authors.forename: Jason
authors.initials: J
authors.lastname: Anderson
authors.forename: Joel K
authors.initials: JK
authors.lastname: Elmquist
authors.forename: Roberto
authors.initials: R
authors.lastname: Coppari
mesh_terms: D000818:Animals; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism* / Q000502:physiology; D001923:Brain Chemistry / Q000502:physiology*; D004734:Energy Metabolism / Q000502:physiology*; D006706:Homeostasis / Q000502:physiology; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008822:Mice, Transgenic; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism* / Q000502:physiology
chemical_list: C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; D037761:Sirtuins