Neurobiology of Rhythms, Institute of Cellular and Integrative Neurosciences, CNRS UPR3212 Associated with University of Strasbourg, Strasbourg, France.
Prog Mol Biol Transl Sci. 2013;119:105-35. doi: 10.1016/B978-0-12-396971-2.00005-1.
Circadian rhythmicity that has been shaped by evolution over millions of years generates an internal timing controlling the sleep-wake and metabolism cycles. The daily variations between sleep/fasting/catabolism and wakefulness/feeding/anabolism are coordinated by a master hypothalamic clock, mainly reset by ambient light. Secondary clocks, including liver and adipose tissue, are normally synchronized by the master clock, but they are also sensitive to feeding time, especially when meals take place during the usual resting period. Cellular metabolism and circadian clocks are tightly interconnected at the molecular levels. Although the suprachiasmatic clock is not shifted by mealtime under light-dark conditions, nutritional cues can feedback onto it and modulate its function under hypo- and hypercaloric (high-fat) conditions. Food-related reward cues are other modulators of the master clock. Circadian disturbances (e.g., desynchronization induced by shift work or chronic jet lag) are frequently associated with metabolic dysfunctions (chronobesity) and vice versa. Pharmacological tools and natural synchronizers (i.e., light and mealtime) can be useful as chronotherapeutic treatments to limit the occurrence of metabolic risk factors.
生物钟节律经过数百万年的进化而形成，它控制着睡眠-觉醒和代谢循环。睡眠/禁食/分解代谢和觉醒/进食/合成代谢之间的日常变化由主下丘脑时钟协调，主要由环境光重置。次要时钟，包括肝脏和脂肪组织，通常由主时钟同步，但它们也对进食时间敏感，尤其是当进餐发生在通常的休息时间时。细胞代谢和生物钟在分子水平上紧密相连。虽然在光暗条件下，用餐时间不会改变视交叉上核时钟，但营养信号可以反馈到其上，并在低卡路里（高脂肪）和高卡路里条件下调节其功能。与食物相关的奖励线索是主时钟的其他调节剂。昼夜节律紊乱（例如，轮班工作或慢性时差反应引起的失同步）常与代谢功能障碍（chronobesity）相关，反之亦然。药理学工具和自然同步器（即光和用餐时间）可作为时间治疗方法有用，以限制代谢危险因素的发生。
