昼夜节律钟调控代谢的研究进展

Progress in the Studies of Circadian Clock Regulating Matabolism

生理和行为的昼夜节律性调控对健康生活是必需的。越来越多的流行病学和遗传学证据显示昼夜节律的破坏与代谢紊乱性疾病相关联。在分子水平上,昼夜节律受到时钟蛋白组成的转录–翻译负反馈环的调控。时钟蛋白通过以下两种途径调节代谢:首先,时钟蛋白作为转录因子直接调节一些代谢关键步骤的限速酶和代谢相关核受体的表达,其次作为代谢相关核受体的辅调节因子来激活或抑制其转录活性。虽然时钟蛋白对代谢途径的调节导致代谢物水平呈昼夜节律振荡,但是产生的代谢物反过来又可以影响昼夜节律钟基因的表达,进而影响昼夜节律钟。深入研究昼夜节律钟与代谢的交互调节可能为治疗某些代谢紊乱性疾病提供新的治疗方案。

Circadian control dence in epidemiological and genetic of physiology and behavior is required for a healthy life. Accumulating evi- suggests that the disruption of circadian rhythm connects to metabolic disor- ders. Circadian rhythm is controlled by circadian clock constituted transcription-translation feedback loop. Circa- dian clock controls the cellular metabolic process by two means as followed. Firstly, circadian clock regulates the expression of enzymes that modulate the rate-limiting steps of metabolic pathways and those nuclear receptors in relation with metabolism; Secondly, circadian clock may interacts with nuclear receptor in metabolism as transcrip- tion co-regulators to activate or repress the expression of metabolic genes. Although circadian clock orchestrates multiple metabolic pathways resulting in the circadian oscillations of metabolites, the availability of metabolites can affect the expression of circadian clock in turn. A further study in the crosstalk of circadian clock and metabolic may provide new therapeutic strategy against metabolic disorders.