The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
SirT1 Gain of Function Increases Energy Efficiency and Prevents Diabetes in Mice
Open accessAbstract
Summary In yeast, worms and flies, an extra copy of the gene encoding the Sirtuin Sir2 increases metabolic efficiency, as does administration of polyphenols like resveratrol, thought to act through Sirtuins. But evidence that Sirtuin gain-of-function results in increased metabolic efficiency in mammals is limited. We generated transgenic mice with moderate overexpression of SirT1, designed to mimic the Sirtuin gain-of-function that improves metabolism in C.elegans. These mice exhibit normal insulin sensitivity, but decreased food intake and locomotor activity, resulting in decreased energy expenditure. However, in various models of insulin resistance and diabetes, SirT1 transgenics display improved glucose tolerance due to decreased hepatic glucose production and increased adiponectin levels, without changes in body weight or composition. We conclude that SirT1 gain-of-function primes the organism for metabolic adaptation to insulin resistance, increasing hepatic insulin sensitivity and decreasing whole-body energy requirements. These findings have important implications for Sirtuin-based therapies in humans.
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Cites
Increased oxidative stress in obesity and its impact on metabolic syndrome
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Resveratrol improves health and survival of mice on a high-calorie diet
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Cloning of adiponectin receptors that mediate antidiabetic metabolic effects
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Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1
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Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes
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“Sirtuin agonists increase metabolic efficiency in rodents through a mechanism bearing similarity with calorie restriction (Baur et al., 2006; Lagouge et al., 2006; Milne et al., 2007).”
Lifetime risk for diabetes mellitus in the United States
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Obesity-associated improvements in metabolic profile through expansion of adipose tissue
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“Nonetheless, this phenotype bears similarities with the effect of adiponectin overexpression in ob/ob mice (Kim et al., 2007).”
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The Mammalian SIR2α Protein Has a Role in Embryogenesis and Gametogenesis
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Cited by
Mammalian Sirtuins: Biological Insights and Disease Relevance
Haigis, M. C., & Sinclair, D. A. (2010) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev.pathol.4.110807.092250 · Cited by 2,085
Cantó, C., Menzies, K. J., & Auwerx, J. (2015) · Cell Metabolism · doi:10.1016/j.cmet.2015.05.023 · Cited by 1,648
PGC-1α, SIRT1 and AMPK, an energy sensing network that controls energy expenditure
Cantó, C., & Auwerx, J. (2009) · Current Opinion in Lipidology · doi:10.1097/mol.0b013e328328d0a4 · Cited by 1,624
Price, N. L., Gomes, A. P., Ling, A. J. Y., Duarte, F. V., Martin-Montalvo, A., North, B. J., Agarwal, B., Ye, L., Ramadori, G., Teodoro, J. S., et al. (2012) · Cell Metabolism · doi:10.1016/j.cmet.2012.04.003 · Cited by 1,602
Purushotham, A., Schug, T. T., Xu, Q., Surapureddi, S., Guo, X., & Li, X. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2009.02.006 · Cited by 1,003
Metadata
- Authors
- Banks, A. S., Kon, N., Knight, C., Matsumoto, M., Gutiérrez-Juárez, R., Rossetti, L., Gu, W., & Accili, D.
- Venue
- Cell Metabolism
- Publisher
- Elsevier BV
- Published
- 2008-10
- Volume
- 8
- Issue
- 4
- Pages
- 333-341
- ISSN
- 1550-4131 (ISSN-L)
- OpenAlex
- W2080192652
- Cited by
- 637
- References
- 11
- FWCI
- 21.63
- Type
- journal article
- Language
- en
- Open access
- bronze
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