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Physiol Rev. 2012 Jul;92(3):1479-514. doi: 10.1152/physrev.00022.2011.

Sirtuin 1 and sirtuin 3: physiological modulators of metabolism.

Author information

1
Department of Physiology, School of Medicine-Instituto de Investigaciones Sanitarias, University of Santiago de Compostela, Santiago de Compostela, Spain.

Abstract

The sirtuins are a family of highly conserved NAD(+)-dependent deacetylases that act as cellular sensors to detect energy availability and modulate metabolic processes. Two sirtuins that are central to the control of metabolic processes are mammalian sirtuin 1 (SIRT1) and sirtuin 3 (SIRT3), which are localized to the nucleus and mitochondria, respectively. Both are activated by high NAD(+) levels, a condition caused by low cellular energy status. By deacetylating a variety of proteins that induce catabolic processes while inhibiting anabolic processes, SIRT1 and SIRT3 coordinately increase cellular energy stores and ultimately maintain cellular energy homeostasis. Defects in the pathways controlled by SIRT1 and SIRT3 are known to result in various metabolic disorders. Consequently, activation of sirtuins by genetic or pharmacological means can elicit multiple metabolic benefits that protect mice from diet-induced obesity, type 2 diabetes, and nonalcoholic fatty liver disease.

PMID:
22811431
PMCID:
PMC3746174
DOI:
10.1152/physrev.00022.2011
[Indexed for MEDLINE]
Free PMC Article

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