University Lille Nord de France, Lille, France.
J Appl Physiol (1985). 2009 Dec;107(6):1972-80. doi: 10.1152/japplphysiol.00570.2009. Epub 2009 Aug 20.
The endogenous circadian clock ensures daily rhythms in diverse behavioral and physiological processes, including locomotor activity and sleep/wake cycles, but also food intake patterns. Circadian rhythms are generated by an internal clock system, which synchronizes these daily variations to the day/night alternance. In addition, circadian oscillations may be reset by the time of food availability in peripheral metabolic organs. Circadian rhythms are seen in many metabolic pathways (glucose and lipid metabolism, etc.) and endocrine secretions (insulin, etc.). As a consequence, misalignment of the internal timing system vs. environmental zeitgebers (light, for instance), as experienced during jetlag or shift work, may result in disruption of physiological cycles of fuel utilization or energy storage. A large body of evidence from both human and animal studies now points to a relationship between circadian disorders and altered metabolic response, suggesting that circadian and metabolic regulatory networks are tightly connected. After a review of the current understanding of the molecular circadian core clock, we will discuss the hypothesis that clock genes themselves link the core molecular clock and metabolic regulatory networks. We propose that the nuclear receptor and core clock component Rev-erb-alpha behaves as a gatekeeper to timely coordinate the circadian metabolic response.
内源性生物钟确保了多种行为和生理过程的日常节律，包括运动活动和睡眠/觉醒周期，但也包括饮食模式。生物钟是由内部时钟系统产生的，它将这些日常变化与日夜交替同步。此外，食物在周围代谢器官中的可用性也可以重置生物钟的振荡。生物钟在许多代谢途径（葡萄糖和脂质代谢等）和内分泌分泌（胰岛素等）中可见。因此，内部计时系统与环境时间信号（例如光）之间的错位，如在倒时差或轮班工作期间经历的那样，可能导致燃料利用或能量储存的生理周期中断。现在，来自人类和动物研究的大量证据表明，生物钟紊乱与代谢反应改变之间存在关系，表明生物钟和代谢调节网络紧密相连。在回顾了当前对分子生物钟核心的理解之后，我们将讨论这样一种假设，即时钟基因本身将核心分子钟和代谢调节网络联系起来。我们提出，核受体和核心时钟成分 Rev-erb-α 作为守门员，适时协调昼夜节律代谢反应。
