Diurnal variation of the human adipose transcriptome and the link to metabolic disease.
Diurnal variation of the human adipose transcriptome and the link to metabolic disease.
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DOI：
10.1186/1755-8794-2-7
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发表时间：
2009-02-09
影响因子：
2.7
通讯作者：
Lum PY
中科院分区：
文献类型：
--
作者：
Loboda A;Kraft WK;Fine B;Joseph J;Nebozhyn M;Zhang C;He Y;Yang X;Wright C;Morris M;Chalikonda I;Ferguson M;Emilsson V;Leonardson A;Lamb J;Dai H;Schadt E;Greenberg HE;Lum PY
昼夜节律是身体生理的一个组成部分；具体来说，睡眠、进食行为和新陈代谢与地球自转所决定的光暗循环密切相关。本研究探讨了昼夜节律对超重至轻度肥胖健康人皮下脂肪组织基因表达的影响。在这项控制良好的临床研究中，在上午、下午和晚上对三个研究组的个体进行了脂肪活检：使用减肥药西布曲明/禁食，安慰剂/喂食和安慰剂/禁食。结果表明，昼夜节律是人类脂肪组织中基因表达变化的最重要驱动因素，至少25%的基因在一天中的表达水平发生了显著变化。核心时钟基因在一天中特定时间的mRNA表达水平在所有三组的不同天中在多个受试者中是一致的，表明无论潜在的混杂因素如何，都有强大的昼夜调节。能量代谢和组织生理所必需的基因是昼夜特征的一部分。我们假设能量代谢基因表达的昼夜转变反映了脂肪组织从早晨的能量消耗状态到晚上的能量储存状态的转变。与这一假设一致，禁食和西布曲明治疗延迟了昼夜转换。最后，通过对来自公开可用的Connectivity Map数据的日特征进行计算机比较，显示了与mTOR抑制剂抑制的转录本之间的显著关联，这表明mTOR信号传导、日基因表达和代谢调节之间可能存在联系。昼夜节律在脂肪组织的生理和能量代谢调节中起着重要作用，在选择治疗肥胖和其他代谢紊乱的新靶点时应予以考虑。
Circadian (diurnal) rhythm is an integral part of the physiology of the body; specifically, sleep, feeding behavior and metabolism are tightly linked to the light-dark cycle dictated by earth's rotation. The present study examines the effect of diurnal rhythm on gene expression in the subcutaneous adipose tissue of overweight to mildly obese, healthy individuals. In this well-controlled clinical study, adipose biopsies were taken in the morning, afternoon and evening from individuals in three study arms: treatment with the weight loss drug sibutramine/fasted, placebo/fed and placebo/fasted. The results indicated that diurnal rhythm was the most significant driver of gene expression variation in the human adipose tissue, with at least 25% of the genes having had significant changes in their expression levels during the course of the day. The mRNA expression levels of core clock genes at a specific time of day were consistent across multiple subjects on different days in all three arms, indicating robust diurnal regulation irrespective of potential confounding factors. The genes essential for energy metabolism and tissue physiology were part of the diurnal signature. We hypothesize that the diurnal transition of the expression of energy metabolism genes reflects the shift in the adipose tissue from an energy-expending state in the morning to an energy-storing state in the evening. Consistent with this hypothesis, the diurnal transition was delayed by fasting and treatment with sibutramine. Finally, an in silico comparison of the diurnal signature with data from the publicly-available Connectivity Map demonstrated a significant association with transcripts that were repressed by mTOR inhibitors, suggesting a possible link between mTOR signaling, diurnal gene expression and metabolic regulation. Diurnal rhythm plays an important role in the physiology and regulation of energy metabolism in the adipose tissue and should be considered in the selection of novel targets for the treatment of obesity and other metabolic disorders.
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影响因子：
4.8
作者：
Allard, David;Figg, Nichola;Littlewood, Trevor D.
通讯作者：
Littlewood, Trevor D.
DOI：
10.1083/jcb.149.3.567
发表时间：
2000-05-01
期刊：
The Journal of cell biology
影响因子：
--
作者：
Ko YG;Kang YS;Kim EK;Park SG;Kim S
通讯作者：
Kim S
DOI：
10.1152/ajpheart.01174.2006
发表时间：
2007-06-01
影响因子：
4.8
作者：
Ma, Kun L.;Ruan, Xiong Z.;Varghese, Zac
通讯作者：
Varghese, Zac
影响因子：
5.8
作者：
He, YDD;Dai, HY;Stoughton, RB
通讯作者：
Stoughton, RB
影响因子：
46.9
作者：
Hughes, TR;Mao, M;Linsley, PS
通讯作者：
Linsley, PS