The Liver in the Eyes of a Chronobiologist
The Liver in the Eyes of a Chronobiologist
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DOI：
10.1177/0748730416633552
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发表时间：
2016-02
影响因子：
3.5
通讯作者：
Ziv Zwighaft;H. Reinke;Gad Asher
中科院分区：
文献类型：
--
作者：
Ziv Zwighaft;H. Reinke;Gad Asher
在过去的几十年里，我们对哺乳动物昼夜节律振荡器的分子基础及其与生理学的紧密联系的理解取得了巨大的进展。肝脏被认为是外周器官昼夜节律研究的原型实验模型组织。对肝钟的研究一直很有成效，并提供了关于昼夜生物学的广泛不同方面的信息。肝脏作为人体最大的器官之一，经常被用来识别核心时钟和辅助时钟组件，例如通过生化提纯。由于肝脏也是主要的代谢中枢，有关生物钟和新陈代谢之间相互作用的研究一直很有见地。此外，对时钟成分使用肝脏特有的功能丧失模型不仅强调了肝脏时钟的特定生理作用，而且还强调了它与其他器官中的全身信号和振荡器的相互作用。最近，组学方法的技术进步已经成功地应用于肝脏，全面描述了普遍存在的对基因表达、蛋白质和代谢物积累的昼夜节律控制。在这篇综述中，我们选择说明具体的例子，这些例子展示了不同的实验方法--即生化、代谢、遗传和组学方法--如何促进了我们对昼夜节律肝脏生物学和一般时间生物学的了解。
Our understanding of the molecular underpinnings of the mammalian circadian oscillator and its tight connection to physiology has progressed tremendously during the past decades. The liver is considered the prototypic experimental model tissue for circadian research in peripheral organs. Studies on liver clocks have been highly productive and yielded information about widely different aspects of circadian biology. The liver, as one of the largest organs in the body, has often been used for the identification of core clock and auxiliary clock components, for example, by biochemical purifications. Because the liver is also a major metabolic hub, studies addressing the interplay between circadian clocks and metabolism have been insightful. In addition, the use of liver-specific loss-of-function models for clock components highlighted not only specific physiological roles of the hepatic clock but also its interplay with systemic cues and oscillators in other organs. Recently, technological advances in omics approaches have been successfully applied on the liver, providing a comprehensive depiction of pervasive circadian control of gene expression and protein and metabolite accumulation. In this review, we chose to illuminate specific examples that demonstrate how different experimental approaches—namely, biochemical, metabolic, genetic, and omics methodologies—have advanced our knowledge regarding circadian liver biology and chronobiology in general.