期刊
CELL METABOLISM
卷 13, 期 4, 页码 461-468出版社
CELL PRESS
DOI: 10.1016/j.cmet.2011.03.004
关键词
-
资金
- Bolyai
- SNSF
- EMBO
- FEBS
- NWO
- NKTH
- OTKA [NFF78498, IN80481]
- Mecenatura [DE OEC Mec-1/2008]
- NIH [DK59820, DK73466]
- ERC [2008-AdG-23118]
- CNRS
- ANR EGIDE [22873YC]
- Ellison Medical Foundation
SIRT1 regulates energy homeostasis by controlling the acetylation status and activity of a number of enzymes and transcriptional regulators. The fact that NAD(+) levels control SIRT1 activity confers a hypothetical basis for the design of new strategies to activate SIRT1 by increasing NAD(+) availability. Here we show that the deletion of the poly(ADPribose) polymerase-1 (PARP-1) gene, encoding a major NAD(+)-consuming enzyme, increases NAD(+) content and SIRT1 activity in brown adipose tissue and muscle. PARP-1(-/-) mice phenocopied many aspects of SIRT1 activation, such as a higher mitochondrial content, increased energy expenditure, and protection against metabolic disease. Also, the pharmacologic inhibition of PARP in vitro and in vivo increased NAD(+) content and SIRT1 activity and enhanced oxidative metabolism. These data show how PARP-1 inhibition has strong metabolic implications through the modulation of SIRT1 activity, a property that could be useful in the management not only of metabolic diseases, but also of cancer.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据