The Synergistic Role of Light-Feeding Phase Relations on Entraining Robust Circadian Rhythms in the Periphery.

Gene regulation and systems biology Pub Date : 2017-04-20 eCollection Date: 2017-01-01 DOI:10.1177/1177625017702393
Seul-A Bae, Ioannis P Androulakis
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引用次数: 29

Abstract

The feeding and fasting cycles are strong behavioral signals that entrain biological rhythms of the periphery. The feeding rhythms synchronize the activities of the metabolic organs, such as liver, synergistically with the light/dark cycle primarily entraining the suprachiasmatic nucleus. The likely phase misalignment between the feeding rhythms and the light/dark cycles appears to induce circadian disruptions leading to multiple physiological abnormalities motivating the need to investigate the mechanisms behind joint light-feeding circadian entrainment of peripheral tissues. To address this question, we propose a semimechanistic mathematical model describing the circadian dynamics of peripheral clock genes in human hepatocyte under the control of metabolic and light rhythmic signals. The model takes the synergistically acting light/dark cycles and feeding rhythms as inputs and incorporates the activity of sirtuin 1, a cellular energy sensor and a metabolic enzyme activated by nicotinamide adenine dinucleotide. The clock gene dynamics was simulated under various light-feeding phase relations and intensities, to explore the feeding entrainment mechanism as well as the convolution of light and feeding signals in the periphery. Our model predicts that the peripheral clock genes in hepatocyte can be completely entrained to the feeding rhythms, independent of the light/dark cycle. Furthermore, it predicts that light-feeding phase relationship is a critical factor in robust circadian oscillations.

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取光期关系对外周强生理节律的协同作用。
进食和禁食周期是一种强烈的行为信号,它会影响周围的生物节律。摄食节律与代谢器官(如肝脏)的活动同步,与主要携带视交叉上核的光/暗循环协同作用。摄食节律和光/暗周期之间可能的相位失调似乎会导致昼夜节律中断,导致多种生理异常,这促使人们有必要研究外周组织联合摄食昼夜节律干扰背后的机制。为了解决这个问题,我们提出了一个半机械的数学模型来描述代谢和光节律信号控制下人类肝细胞外周时钟基因的昼夜动力学。该模型以协同作用的光/暗周期和摄食节律为输入,并结合了sirtuin 1的活性,sirtuin 1是一种细胞能量传感器,是一种由烟酰胺腺嘌呤二核苷酸激活的代谢酶。在不同的供光相位关系和强度下,模拟时钟基因的动态,探索供光夹带机制以及光和供光信号在外围的卷积。我们的模型预测,肝细胞中的外周时钟基因可以完全受摄食节律的影响,独立于光/暗周期。此外,它预测了光摄食相位关系是稳健的昼夜节律振荡的关键因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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