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Regulation of Mammalian Physiology by Interconnected Circadian and Feeding Rhythms.

机译:相互联系的昼夜节律和喂养节奏对哺乳动物生理的调节。

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摘要

Circadian clocks are endogenous timekeeping systems that adapt in an anticipatory fashion the physiology and behavior of most living organisms. In mammals, the master pacemaker resides in the suprachiasmatic nucleus and entrains peripheral clocks using a wide range of signals that differentially schedule physiology and gene expression in a tissue-specific manner. The peripheral clocks, such as those found in the liver, are particularly sensitive to rhythmic external cues like feeding behavior, which modulate the phase and amplitude of rhythmic gene expression. Consequently, the liver clock temporally tunes the expression of many genes involved in metabolism and physiology. However, the circadian modulation of cellular functions also relies on multiple layers of posttranscriptional and posttranslational regulation. Strikingly, these additional regulatory events may happen independently of any transcriptional oscillations, showing that complex regulatory networks ultimately drive circadian output functions. These rhythmic events also integrate feeding-related cues and adapt various metabolic processes to food availability schedules. The importance of such temporal regulation of metabolism is illustrated by metabolic dysfunctions and diseases resulting from circadian clock disruption or inappropriate feeding patterns. Therefore, the study of circadian clocks and rhythmic feeding behavior should be of interest to further advance our understanding of the prevention and therapy of metabolic diseases.
机译:昼夜节律钟是内生的计时系统,以预期的方式适应大多数活生物体的生理和行为。在哺乳动物中,主起搏器位于视交叉上核中,并使用多种信号以特定的生理学和基因表达方式以组织特异性方式夹带周围时钟。外围时钟(例如在肝脏中发现的时钟)对有节奏的外部提示(如进食行为)特别敏感,这些提示会调节有节奏的基因表达的相位和幅度。因此,肝脏时钟在时间上调节了涉及代谢和生理的许多基因的表达。然而,细胞功能的昼夜节律调节也依赖于转录后和翻译后调控的多层。令人惊讶的是,这些额外的调节事件可能独立于任何转录振荡而发生,表明复杂的调节网络最终驱动了昼夜节律的输出功能。这些有节奏的事件还整合了与喂养有关的线索,并使各种代谢过程适应食物的供应时间表。这种代谢的暂时调节的重要性通过昼夜节律紊乱或不适当的喂养方式引起的代谢功能障碍和疾病得以说明。因此,研究昼夜节律和节律性喂养行为应引起人们的兴趣,以进一步提高我们对代谢疾病的预防和治疗的认识。

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