ABSTRACT

In most organisms ranging from cyanobacteria to humans, the endogenous timekeeping system temporally coordinates the behavioral, physiological, and metabolic processes with a periodicity close to 24 h. The timing of these daily rhythms is orchestrated by the synchronized oscillations of both the central pacemaker in the brain and the peripheral clocks located across multiple organs and tissues. A growing body of evidence suggests that the central circadian clock and peripheral clocks residing in the metabolically active tissues are incredibly well coordinated to confer coherent metabolic homeostasis. The interplay between nutrient metabolism and circadian rhythms can occur at various levels supported by the molecular clock network, multiple systemic mechanisms, and the neuroendocrine signaling pathways. While studies suggest the reciprocal regulation between circadian clock and metabolism, it is important to understand the precise mechanisms and the underlying pathways involved in the cross-talk among circadian oscillators and diverse metabolic networks. In addition to the internal synchronization of the metabolic rhythms, feeding time is considered as a potential external synchronization cue that fine tunes the timing of the circadian rhythms in metabolic peripheral clocks. A deeper understanding of how the timing of food intake and the diet composition drive the tissue-specific metabolic rhythms across the body is concomitantly important to develop novel therapeutic strategies for the metabolic disorders arising from circadian misalignment. This review summarizes the recent advancements in the circadian clock regulation of nutrient metabolism and discusses the current understanding of the metabolic feedback signals that link energy metabolism with the circadian clock.

摘要

在从蓝藻到人类的大多数生物体中，内源性计时系统以接近 24 小时的周期在时间上协调行为、生理和代谢过程。这些日常节律的时间安排是由大脑中的中央起搏器和位于多个器官和组织的外围时钟的同步振荡来协调的。越来越多的证据表明，位于代谢活跃组织中的中央生物钟和外周时钟非常协调，以赋予连贯的代谢稳态。营养代谢和昼夜节律之间的相互作用可以在分子时钟网络、多种系统机制和神经内分泌信号通路支持的不同水平上发生。虽然研究表明生物钟和新陈代谢之间存在相互调节，但了解生物钟振荡器和不同代谢网络之间串扰的确切机制和潜在途径非常重要。除了代谢节律的内部同步外，进食时间被认为是一种潜在的外部同步线索，可以微调代谢外围时钟中昼夜节律的时间。深入了解食物摄入时间和饮食成分如何驱动全身组织特异性代谢节律对于开发针对由昼夜节律失调引起的代谢紊乱的新治疗策略同样重要。