Ramsey K M, Bass J
Division of Endocrinology, Metabolism and Molecular Medicine, Feinberg School of Medicine and Department of Neurobiology and Physiology, Northwestern University, Chicago, Illinois 60611-3015, USA.
Cold Spring Harb Symp Quant Biol. 2011;76:63-72. doi: 10.1101/sqb.2011.76.010546. Epub 2011 Sep 2.
Circadian systems have evolved in plants, eubacteria, neurospora, and the metazoa as a mechanism to optimize energy acquisition and storage in synchrony with the rotation of the Earth on its axis. In plants, circadian clocks drive the expression of genes involved in oxygenic photosynthesis during the light and nitrogen fixation during the dark, repeating this cycle each day. In mammals, the core clock in the suprachiasmatic nucleus (SCN) functions to entrain extra-SCN and peripheral clocks to the light cycle, including regions central to energy homeostasis and sleep, as well as peripheral tissues involved in glucose and lipid metabolism. Tissue-specific gene targeting has shown a primary role of clock genes in endocrine pancreas insulin secretion, indicating that local clocks play a cell-autonomous role in organismal homeostasis. A present focus is to dissect the consequences of clock disruption on modulation of nuclear hormone receptor signaling and on posttranscriptional regulation of intermediary metabolism. Experimental genetic studies have pointed toward extensive interplay between circadian and metabolic systems and offer a means to dissect the impact of local tissue molecular clocks on fuel utilization across the sleep-wake cycle.
生物钟系统在植物、真细菌、脉孢菌和后生动物中不断进化，成为一种与地球自转轴旋转同步优化能量获取和储存的机制。在植物中，生物钟驱动着参与光期间的放氧光合作用和暗期间的固氮作用的基因表达，每天重复这个循环。在哺乳动物中，视交叉上核（SCN）中的核心生物钟发挥作用，使SCN外和外周生物钟与光周期同步，包括对能量稳态和睡眠至关重要的区域，以及参与葡萄糖和脂质代谢的外周组织。组织特异性基因靶向研究表明，生物钟基因在内分泌胰腺胰岛素分泌中起主要作用，这表明局部生物钟在机体稳态中发挥细胞自主作用。目前的一个重点是剖析生物钟紊乱对核激素受体信号调节以及中间代谢转录后调控的影响。实验性遗传学研究表明昼夜节律系统和代谢系统之间存在广泛的相互作用，并提供了一种方法来剖析局部组织分子生物钟对整个睡眠-觉醒周期中燃料利用的影响。
