Laboratory of Signal Transduction, National Institute of Environmental Health Sciences, National Institutes of Health, RTP, NC 27709, USA.
Ann Med. 2011 May;43(3):198-211. doi: 10.3109/07853890.2010.547211. Epub 2011 Feb 24.
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.
Sirtuin 1（SIRT1）是酵母 Sir2 的哺乳动物同源物，是一种高度保守的 NAD（+）依赖性蛋白去乙酰化酶，已成为将环境营养信号直接与动物代谢稳态联系起来的关键代谢传感器。已知 SIRT1 参与肝脏中的糖异生、白色脂肪组织中的脂肪动员以及胰腺中的胰岛素分泌。最近的研究表明，SIRT1 调节肝脏中的脂肪酸氧化，感知下丘脑的营养可用性，影响巨噬细胞中肥胖引起的炎症，并调节代谢组织中生物钟的活性。SIRT1 的活性似乎也受到 AMPK 和脂联素的控制。本篇综述重点介绍了 SIRT1 在调节与肥胖相关的代谢疾病中的作用。它简要概述了 Sirtuin 信号通路，重点介绍了 SIRT1 在肝脏、巨噬细胞、大脑和脂肪组织中的作用，因为这些与肥胖有关。
