Brain SIRT1

Anatomical distribution and regulation by energy availability

Giorgio Ramadori, Charlotte E. Lee, Angie L. Bookout, Syann Lee, Kevin W. Williams, Jason Anderson, Joel K. Elmquist, Roberto Coppari

Research output: Contribution to journalArticle

182 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)9989-9996
Number of pages8
JournalJournal of Neuroscience
Volume28
Issue number40
DOIs
StatePublished - Oct 1 2008

Fingerprint

Brain
Messenger RNA
Homeostasis
Area Postrema
Mediodorsal Thalamic Nucleus
Ideal Body Weight
Obese Mice
Pro-Opiomelanocortin
Rhombencephalon
Arcuate Nucleus of Hypothalamus
Solitary Nucleus
Niacinamide
Paraventricular Hypothalamic Nucleus
Genetic Models
Leptin
Energy Intake
Adenosine
Hypothalamus
Reverse Transcription
In Situ Hybridization

Keywords

  • Activity
  • Brain
  • Distribution
  • Obesity
  • Regulation
  • SIRT1

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Brain SIRT1 : Anatomical distribution and regulation by energy availability. / Ramadori, Giorgio; Lee, Charlotte E.; Bookout, Angie L.; Lee, Syann; Williams, Kevin W.; Anderson, Jason; Elmquist, Joel K.; Coppari, Roberto.

In: Journal of Neuroscience, Vol. 28, No. 40, 01.10.2008, p. 9989-9996.

Research output: Contribution to journalArticle

Ramadori, Giorgio ; Lee, Charlotte E. ; Bookout, Angie L. ; Lee, Syann ; Williams, Kevin W. ; Anderson, Jason ; Elmquist, Joel K. ; Coppari, Roberto. / Brain SIRT1 : Anatomical distribution and regulation by energy availability. In: Journal of Neuroscience. 2008 ; Vol. 28, No. 40. pp. 9989-9996.
@article{4743229761374f92987c665b27b421e1,
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.",
keywords = "Activity, Brain, Distribution, Obesity, Regulation, SIRT1",
author = "Giorgio Ramadori and Lee, {Charlotte E.} and Bookout, {Angie L.} and Syann Lee and Williams, {Kevin W.} and Jason Anderson and Elmquist, {Joel K.} and Roberto Coppari",
year = "2008",
month = "10",
day = "1",
doi = "10.1523/JNEUROSCI.3257-08.2008",
language = "English (US)",
volume = "28",
pages = "9989--9996",
journal = "Journal of Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "40",

}

TY - JOUR

T1 - Brain SIRT1

T2 - Anatomical distribution and regulation by energy availability

AU - Ramadori, Giorgio

AU - Lee, Charlotte E.

AU - Bookout, Angie L.

AU - Lee, Syann

AU - Williams, Kevin W.

AU - Anderson, Jason

AU - Elmquist, Joel K.

AU - Coppari, Roberto

PY - 2008/10/1

Y1 - 2008/10/1

N2 - 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.

AB - 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.

KW - Activity

KW - Brain

KW - Distribution

KW - Obesity

KW - Regulation

KW - SIRT1

UR - http://www.scopus.com/inward/record.url?scp=54049158932&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=54049158932&partnerID=8YFLogxK

U2 - 10.1523/JNEUROSCI.3257-08.2008

DO - 10.1523/JNEUROSCI.3257-08.2008

M3 - Article

VL - 28

SP - 9989

EP - 9996

JO - Journal of Neuroscience

JF - Journal of Neuroscience

SN - 0270-6474

IS - 40

ER -