sirt1 regulates energy metabolism and response to caloric restriction in micesirt1调节能量代谢和反应热量限制的老鼠.pdfVIP

SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice 1 2 2 1 1 2 Gino Boily , Erin L. Seifert , Lisa Bevilacqua , Xiao Hong He , Guillaume Sabourin , Carmen Estey , 1 1 1 1 2 2 Cynthia Moffat , Sean Crawford , Sarah Saliba , Karen Jardine , Jian Xuan , Meredith Evans , Mary-Ellen Harper2, Michael W. McBurney1,2* 1 Center for Cancer Therapeutics, Ottawa Health Research Institute, Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada, 2 Department of Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, Ontario, Canada 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. Citation: Boily G, Seifert EL, Bevilacqua L, He XH, Sabourin G, et al. (2008) SirT1 Reg