Ecole Polytechnique Fédérale de Lausanne, Laboratory of Integrative and Systems Physiology and Nestlé Chair in Energy Metabolism, 1015 Lausanne, Switzerland.
EMBO Rep. 2011 Sep 30;12(10):1069-76. doi: 10.1038/embor.2011.151.
The nicotinamide adenine dinucleotide (NAD(+))-dependent deacetylase SIRT1 is a major metabolic regulator activated by energy stresses such as fasting or calorie restriction. SIRT1 activation during fasting not only relies on the increase in the NAD(+)/NADH ratio caused by energy deprivation but also involves an upregulation of SIRT1 mRNA and protein levels in various metabolic tissues. We demonstrate that SIRT1 expression is controlled systemically by the activation of the cyclic AMP response-element-binding protein upon low nutrient availability. Conversely, in the absence of energetic stress, the carbohydrate response-element-binding protein represses the expression of SIRT1. Altogether, these results demonstrate that SIRT1 expression is tightly controlled at the transcriptional level by nutrient availability and further underscore that SIRT1 is a crucial metabolic checkpoint connecting the energetic status with transcriptional programmes.
烟酰胺腺嘌呤二核苷酸（NAD(+))-依赖性去乙酰化酶 SIRT1 是一种主要的代谢调节剂，可被禁食或热量限制等能量应激激活。在禁食期间，SIRT1 的激活不仅依赖于能量剥夺引起的 NAD(+)/NADH 比例增加，还涉及各种代谢组织中 SIRT1 mRNA 和蛋白质水平的上调。我们证明，SIRT1 的表达受全身系统调控，由低营养可用性下环磷酸腺苷反应元件结合蛋白的激活所控制。相反，在没有能量应激的情况下，碳水化合物反应元件结合蛋白会抑制 SIRT1 的表达。总之，这些结果表明，SIRT1 的表达在转录水平上受到营养可用性的严格控制，进一步强调 SIRT1 是连接能量状态和转录程序的关键代谢检查点。
