Circadian clocks are resounding in peripheral tissues.
Circadian clocks are resounding in peripheral tissues.
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DOI：
10.1371/journal.pcbi.0020016
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发表时间：
2006-03
影响因子：
4.3
通讯作者：
Gimble, Jeffrey M
中科院分区：
文献类型：
--
作者：
Ptitsyn, Andrey A;Zvonic, Sanjin;Conrad, Steven A;Scott, L Keith;Mynatt, Randall L;Gimble, Jeffrey M
昼夜节律在大多数生物体中普遍存在。在生物体水平上，即使是不同组织之间昼夜节律基因表达模式的协调中最小的干扰也会导致功能性失调，并可能导致广泛的生理障碍。据报道，外周组织中多达5%-10%的转录基因遵循昼夜表达模式。我们对代表三种不同外周组织的大型数据集进行了昼夜节律基因表达的全面研究。这些数据是在一个大规模的微阵列实验中产生的，该实验覆盖了小鼠白色和棕色脂肪组织以及肝脏中重复的每日循环。我们已经应用了三种替代算法的方法来确定时间序列表达谱的昼夜节律振荡。我们自己的数据分析表明，在小鼠肝脏中，以及在白色和棕色脂肪组织中，至少7%至21%的活性基因的表达遵循每日振荡模式。事实上，对其他实验室数据的分析表明，在肝脏中具有振荡模式的基因的百分比可能接近50%。对于其余的基因，振荡似乎被随机噪声所掩盖。基于多个数据集的相位分类和计算机模拟研究表明，基因的振荡和非振荡部分之间没有可检测的边界。我们的结论是，应给予更多的关注，昼夜节律机制的潜在影响，任何生物代谢和肥胖相关的途径。生物体的新陈代谢在24小时的每日周期中以振荡的方式变化。这种“峰”和“谷”表达的重复模式被称为“昼夜节律”。我们现在知道，人体的内部时钟是由一组离散的基因控制的。这些重要的调节因子存在于身体的许多不同器官中，它们控制着身体中许多其他基因的表达。使用小鼠作为实验动物，Ptitsyn及其同事使用三种不同的数学测试来观察脂肪组织和肝脏中基因表达的整体模式。他们提供的数据表明，大多数活跃的基因在24小时内有节奏地波动。这项工作表明，未来的研究应密切关注昼夜节律在肥胖和脂肪代谢中的影响。
Circadian rhythms are prevalent in most organisms. Even the smallest disturbances in the orchestration of circadian gene expression patterns among different tissues can result in functional asynchrony, at the organism level, and may to contribute to a wide range of physiologic disorders. It has been reported that as many as 5%–10% of transcribed genes in peripheral tissues follow a circadian expression pattern. We have conducted a comprehensive study of circadian gene expression on a large dataset representing three different peripheral tissues. The data have been produced in a large-scale microarray experiment covering replicate daily cycles in murine white and brown adipose tissues as well as in liver. We have applied three alternative algorithmic approaches to identify circadian oscillation in time series expression profiles. Analyses of our own data indicate that the expression of at least 7% to 21% of active genes in mouse liver, and in white and brown adipose tissues follow a daily oscillatory pattern. Indeed, analysis of data from other laboratories suggests that the percentage of genes with an oscillatory pattern may approach 50% in the liver. For the rest of the genes, oscillation appears to be obscured by stochastic noise. Our phase classification and computer simulation studies based on multiple datasets indicate no detectable boundary between oscillating and non-oscillating fractions of genes. We conclude that greater attention should be given to the potential influence of circadian mechanisms on any biological pathway related to metabolism and obesity. The metabolism of living organisms changes over the twenty-four hour daily cycle in an oscillatory manner. This repeating pattern of “peak” and “trough” expression is known as a “circadian rhythm.” We now know that the body's internal clock is controlled by a discrete group of genes. These important regulators are found in many different organs of the body, and they control expression of many other genes in the body. Using mice as an experimental animal, Ptitsyn and colleagues looked at the overall pattern of gene expression in fat tissues and the liver using three different mathematical tests. They present data indicating that the majority of active genes fluctuate rhythmically over a twenty-four hour period. This work suggests that future studies should pay close attention to the influence of the circadian rhythm in obesity and in fat metabolism.