Sirtuin 1 in lipid metabolism and obesity

Abstract

Sirtuin 1 (SIRT1), the mammalian ortholog of yeast Sir2, is a highly conserved NAD⁺-dependent protein deacetylase that has emerged as a key metabolic sensor that directly links environmental nutrient signals to animal metabolic homeostasis. SIRT1 is known to be involved in gluconeogenesis in the liver, fat mobilization in white adipose tissue, and insulin secretion in the pancreas. Recent studies have shown SIRT1 to regulate fatty acid oxidation in the liver, sense nutrient availability in the hypothalamus, influence obesity-induced inflammation in macrophages, and modulate the activity of the circadian clock in metabolic tissues. The activity of SIRT1 also appears to be under the control of AMPK and adiponectin. This review focuses on the involvement of SIRT1 in regulating metabolic diseases associated with obesity. It includes brief overviews of sirtuin signaling, with emphasis on SIRT1's role in the liver, macrophage, brain, and adipose tissue as it relates to obesity.

Key words::

• Metabolic syndrome
• metabolism
• SIRT1

Acknowledgements

We thank Drs Anton Jetten, Huiming Gao, and John Cidlowski for critical reading of the manuscript and NIEHS Multimedia Services Department for the cartoon graph of the figures. The work related to this article was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences to XL (Z01 ES102205).

Declaration of interest: The authors of this manuscript have no conflict of interests to declare.