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大鼠腹部脂肪组织基因表达的昼夜节律变化及其与生理学的关系。

Circadian variations in gene expression in rat abdominal adipose tissue and relationship to physiology.

机构信息

Department of Biological Sciences, State University of New York at Buffalo, Buffalo, NY 14260, USA.

出版信息

Physiol Genomics. 2010 Oct;42A(2):141-52. doi: 10.1152/physiolgenomics.00106.2010. Epub 2010 Aug 3.

Abstract

Circadian rhythms occur in all levels of organization from expression of genes to complex physiological processes. Although much is known about the mechanism of the central clock in the suprachiasmatic nucleus, the regulation of clocks present in peripheral tissues as well as the genes regulated by those clocks is still unclear. In this study, the circadian regulation of gene expression was examined in rat adipose tissue. A rich time series involving 54 animals euthanized at 18 time points within the 24-h cycle (12:12 h light-dark) was performed. mRNA expression was examined with Affymetrix gene array chips and quantitative real-time PCR, along with selected physiological measurements. Transcription factors involved in the regulation of central rhythms were examined, and 13 showed circadian oscillations. Mining of microarray data identified 190 probe sets that showed robust circadian oscillations. Circadian regulated probe sets were further parsed into seven distinct temporal clusters, with >70% of the genes showing maximum expression during the active/dark period. These genes were grouped into eight functional categories, which were examined within the context of their temporal expression. Circadian oscillations were also observed in plasma leptin, corticosterone, insulin, glucose, triglycerides, free fatty acids, and LDL cholesterol. Circadian oscillation in these physiological measurements along with the functional categorization of these genes suggests an important role for circadian rhythms in controlling various functions in white adipose tissue including adipogenesis, energy metabolism, and immune regulation.

摘要

昼夜节律存在于从基因表达到复杂生理过程的所有组织层次中。尽管人们对视交叉上核中央时钟的机制有了很多了解,但外周组织中时钟的调节以及受这些时钟调节的基因仍不清楚。在这项研究中,研究了大鼠脂肪组织中基因表达的昼夜节律调节。进行了一项涉及 54 只动物的丰富时间序列研究,这些动物在 24 小时周期(12:12 光照-黑暗)内的 18 个时间点被安乐死。使用 Affymetrix 基因芯片和定量实时 PCR 以及选定的生理测量方法检查了 mRNA 表达。检查了参与中央节律调节的转录因子,其中 13 个显示出昼夜节律波动。对微阵列数据进行挖掘,确定了 190 个显示出强烈昼夜节律波动的探针集。进一步将昼夜节律调节的探针集解析为七个不同的时间簇,其中 >70%的基因在活动/黑暗期间表达最高。这些基因被分为八个功能类别,并在其时间表达的背景下进行了检查。血浆瘦素、皮质酮、胰岛素、葡萄糖、甘油三酯、游离脂肪酸和 LDL 胆固醇也存在昼夜节律波动。这些生理测量的昼夜节律波动以及这些基因的功能分类表明,昼夜节律在控制白色脂肪组织中的各种功能方面发挥着重要作用,包括脂肪生成、能量代谢和免疫调节。

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