卡路里限制对SIRT1的组织特异性调节。
Tissue-specific regulation of SIRT1 by calorie restriction.
作者信息
Chen Danica, Bruno Joanne, Easlon Erin, Lin Su-Ju, Cheng Hwei-Ling, Alt Frederick W, Guarente Leonard
机构信息
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
出版信息
Genes Dev. 2008 Jul 1;22(13):1753-7. doi: 10.1101/gad.1650608. Epub 2008 Jun 11.
Abstract
Calorie restriction (CR) has been reported to increase SIRT1 protein levels in mice, rats, and humans, and elevated activity of SIRT1 orthologs extends life span in yeast, worms, and flies. In this study, we challenge the paradigm that CR induces SIRT1 activity in all tissues by showing that activity of this sirtuin in the liver is, in fact, reduced by CR and activated by a high-caloric diet. We demonstrate this change both by assaying levels of SIRT1 and its small molecule regulators, NAD and NADH, as well as assessing phenotypes of a liver-specific SIRT1 knockout mouse on various diets. Our findings suggest that designing CR mimetics that target SIRT1 to provide uniform systemic benefits may be more complex than currently imagined.
摘要
据报道，热量限制（CR）可提高小鼠、大鼠和人类体内的SIRT1蛋白水平，而SIRT1直系同源物活性的提高可延长酵母、蠕虫和果蝇的寿命。在本研究中，我们对“CR在所有组织中诱导SIRT1活性”这一范式提出质疑，因为我们发现，实际上CR会降低肝脏中这种去乙酰化酶的活性，而高热量饮食则会激活它。我们通过检测SIRT1及其小分子调节剂NAD和NADH的水平，以及评估肝脏特异性SIRT1基因敲除小鼠在不同饮食条件下的表型，证明了这种变化。我们的研究结果表明，设计靶向SIRT1以提供统一全身益处的CR模拟物可能比目前想象的更为复杂。
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本文引用的文献
1
Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes.作为治疗2型糖尿病的疗法的SIRT1小分子激活剂。
Nature. 2007 Nov 29;450(7170):712-6. doi: 10.1038/nature06261.
2
SIRT1 deacetylates and positively regulates the nuclear receptor LXR.沉默调节蛋白1使核受体肝X受体去乙酰化并对其起正向调节作用。
Mol Cell. 2007 Oct 12;28(1):91-106. doi: 10.1016/j.molcel.2007.07.032.
3
SIRT1 improves insulin sensitivity under insulin-resistant conditions by repressing PTP1B.在胰岛素抵抗条件下，沉默调节蛋白1（SIRT1）通过抑制蛋白酪氨酸磷酸酶1B（PTP1B）来提高胰岛素敏感性。
Cell Metab. 2007 Oct;6(4):307-19. doi: 10.1016/j.cmet.2007.08.014.
4
Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1.通过肝脏沉默调节蛋白1的禁食依赖性葡萄糖和脂质代谢反应。
Proc Natl Acad Sci U S A. 2007 Jul 31;104(31):12861-6. doi: 10.1073/pnas.0702509104. Epub 2007 Jul 23.
5
Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1alpha.通过SIRT1/PGC-1α对肌肉线粒体功能和脂肪酸氧化进行代谢控制。
EMBO J. 2007 Apr 4;26(7):1913-23. doi: 10.1038/sj.emboj.7601633. Epub 2007 Mar 8.
6
Calorie restriction increases muscle mitochondrial biogenesis in healthy humans.热量限制可增加健康人的肌肉线粒体生物合成。
PLoS Med. 2007 Mar;4(3):e76. doi: 10.1371/journal.pmed.0040076.
7
Lipid metabolism in the liver.肝脏中的脂质代谢。
Z Gastroenterol. 2007 Jan;45(1):35-41. doi: 10.1055/s-2006-927368.
8
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9
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Trends Mol Med. 2007 Feb;13(2):64-71. doi: 10.1016/j.molmed.2006.12.004. Epub 2007 Jan 4.
10
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Cell. 2006 Dec 15;127(6):1109-22. doi: 10.1016/j.cell.2006.11.013. Epub 2006 Nov 16.
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