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The Journal of Neuroscience, October 1, 2008, 28(40):9989-9996; doi:10.1523/JNEUROSCI.3257-08.2008

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Behavioral/Systems/Cognitive
Brain SIRT1: Anatomical Distribution and Regulation by Energy Availability

Giorgio Ramadori,¹ Charlotte E. Lee,¹ Angie L. Bookout,^1,2 * Syann Lee,^1 * Kevin W. Williams,¹ Jason Anderson,¹ Joel K. Elmquist,^1,2 and Roberto Coppari¹

¹Department of Internal Medicine, Division of Hypothalamic Research, and ²Department of Pharmacology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9077

Correspondence should be addressed to Dr. Roberto Coppari, Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Room Y6-220C, Dallas, TX 75390-9077. Email: roberto.coppari{at}utsouthwestern.edu

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.

Key words: SIRT1; distribution; regulation; activity; brain; obesity

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Received July 12, 2008; accepted Aug. 27, 2008.

Correspondence should be addressed to Dr. Roberto Coppari, Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Room Y6-220C, Dallas, TX 75390-9077. Email: roberto.coppari{at}utsouthwestern.edu

This article has been cited by other articles:

				G. Ramadori, L. Gautron, T. Fujikawa, C. R. Vianna, J. K. Elmquist, and R. Coppari Central Administration of Resveratrol Improves Diet-Induced Diabetes Endocrinology, December 1, 2009; 150(12): 5326 - 5333. [Abstract] [Full Text] [PDF]

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