Circadian rhythm of clock genes in human adipose explants.

Circadian rhythm of clock genes in human adipose explants.
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人脂肪外植体中时钟基因的昼夜节律。

DOI:
10.1038/oby.2009.164
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发表时间:
2009-08
期刊:
影响因子:
6.9
通讯作者:
Garaulet, Marta
Garaulet, Marta
中科院分区:
医学2区
文献类型:
--
作者:
Gomez-Santos, Cecilia;Gomez-Abellan, Purificacion;Madrid, Juan A.;Hernandez-Morante, Juan J.;Lujan, Juan A.;Ordovas, Jose M.;Garaulet, Marta

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分析严重肥胖女性外植体中时钟基因hPer2、hBMal1和hCry1在皮下和内脏脂肪组织中的昼夜表达,以阐明这种昼夜节律是否能够准确地独立于视交叉上核振荡,以及糖皮质激素代谢相关基因如糖皮质激素受体和11β-羟基类固醇脱氢酶1(H11β5Hsd1)和转录因子过氧化体激活受体γ(hPPARγ)是否是时钟控制基因的一部分。AT活检来自病态肥胖患者(BMI和GT;40 kg/m2)(n=7)。测量人体测量学变量,分析空腹血脂和脂蛋白浓度。为了进行节律表达分析,在24 h内培养AT外植体,并在0、6、12和18h(T)用实时定量聚合酶链式反应(RT-PCR)进行基因表达。在AT外植体中,时钟基因的振荡准确且不依赖于SCN。它们的内在振荡机制调节其他基因的时序,如hPPAR、γ和糖皮质激素相关基因。VAT和SAT的昼夜节律模式不同。遗传昼夜节律振荡与代谢综合征各成分的相关分析显示,矢状径越大的受试者,hPer2表达的昼夜变异性越强(r=0.91P=0.031),hBMal1表达的昼夜变异性也越强(r=0.9;P=0.040)。数据表明,在人类AT中存在独立于中枢昼夜节律控制机制的外周昼夜节律振荡器。这一知识为更好地理解昼夜节律对肥胖和METS等医学状况的影响铺平了道路。
To analyze in severely obese women the circadian expression of the clock genes hPer2, hBmal1, and hCry1 in explants from subcutaneous (SAT) and visceral (VAT) adipose tissue (AT), in order to elucidate whether this circadian clockwork can oscillate accurately and independently of the suprachiasmatic nucleus (SCN) and if glucocorticoid metabolism-related genes such as glucocorticoid receptor (hGr) and 11β-hydroxysteroid dehydrogenase 1 (h11β5Hsd1) and the transcription factor peroxisome proliferator activated receptor γ (hPPARγ) are part of the clock controlled genes. AT biopsies were obtained from morbid obese patients (BMI >40 kg/m2) (n = 7). Anthropometric variables were measured and fasting plasma lipids and lipoprotein concentrations were analyzed. In order to carry out rhythmic expression analysis, AT explants were cultured during 24 h and gene expression was performed at the following times (T): 0, 6, 12, and 18 h, with quantitative real-time PCR. Clock genes oscillated accurately and independently of the SCN in AT explants. Their intrinsic oscillatory mechanism regulated the timing of other genes such as hPPARγ and glucocorticoid-related genes. Circadian patterns differed between VAT and SAT. Correlation analyses between the genetic circadian oscillation and components of the metabolic syndrome (MetS) revealed that subjects with a higher sagittal diameter showed an increased circadian variability in hPer2 expression (r = 0.91; P = 0.031) and hBmal1 (r = 0.90; P = 0.040). Data demonstrate the presence of peripheral circadian oscillators in human AT independently of the central circadian control mechanism. This knowledge paves the way for a better understanding of the circadian contribution to medical conditions such as obesity and MetS.
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