SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice

Gino Boily,Michael W Mcburney,Cynthia Moffat,Erin L Seifert,Meredith Evans,Sean Crawford,Karen Jardine,Xiao Hong He,Lisa Bevilacqua,Jian Xuan,Guillaume Sabourin,Sarah Saliba,Mary-Ellen Harper,Carmen Estey,Edathara Abraham

doi:10.1371/journal.pone.0001759

Gino Boily, Michael W Mcburney + Show 13 more

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https://doi.org/10.1371/journal.pone.0001759

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Journal: PloS one	Publication Date: Mar 12, 2008
Citations: 472	License type: CC BY 4.0

Affiliation: University of Ottawa, Ottawa University

Abstract

The yeast sir2 gene and its orthologues in Drosophila and C. elegans have well-established roles in lifespan determination and response to caloric restriction. We have studied mice carrying two null alleles for SirT1, the mammalian orthologue of sir2, and found that these animals inefficiently utilize ingested food. These mice are hypermetabolic, contain inefficient liver mitochondria, and have elevated rates of lipid oxidation. When challenged with a 40% reduction in caloric intake, normal mice maintained their metabolic rate and increased their physical activity while the metabolic rate of SirT1-null mice dropped and their activity did not increase. Moreover, CR did not extend lifespan of SirT1-null mice. Thus, SirT1 is an important regulator of energy metabolism and, like its orthologues from simpler eukaryotes, the SirT1 protein appears to be required for a normal response to caloric restriction.

Highlights

Silent information regulator 2 is a yeast gene encoding a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase [1,2]
When daily food intake is normalized to body weight (BWT), it is evident that the SirT1null mice are hyperphagic (Figure 1C)
This difference in food intake is not caused by inefficient food absorption by the digestive tract as bomb calorimetry of fecal material from SirT1-null and normal mice were depleted of calories (Figure 1D)

Summary

Introduction

Silent information regulator 2 (sir2) is a yeast gene encoding a nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase [1,2]. Homologues of this protein are found throughout prokaryotes and eukaryotes [3]. SirT1 is the family member sharing the most homology to Sir2 [8] and is considered to be its orthologue. It is not known whether SirT1 is involved in aging it is frequently assumed to share this role with its sir orthologues. SirT1 can deacetylate histones [1,9] as well as a wide variety of nuclear and cytoplasmic proteins (reviewed in [10])

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Results

Conclusion