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进食时间不规律会打破棕色脂肪组织内部以及外周时钟之间的昼夜节律。

Misaligned feeding uncouples daily rhythms within brown adipose tissue and between peripheral clocks.

机构信息

Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA.

Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX 75390-9111, USA; Berkeley Public Health, Molecular Cell Biology Department, University of California, Berkeley, Berkeley, CA, USA.

出版信息

Cell Rep. 2024 Aug 27;43(8):114523. doi: 10.1016/j.celrep.2024.114523. Epub 2024 Jul 23.

Abstract

Extended food consumption during the rest period perturbs the phase relationship between circadian clocks in the periphery and the brain, leading to adverse health effects. Beyond the liver, how metabolic organs respond to a timed hypocaloric diet is largely unexplored. We investigated how feeding schedules impacted circadian gene expression in epididymal white and brown adipose tissue (eWAT and BAT) compared to the liver and hypothalamus. We restricted food to either daytime or nighttime in C57BL/6J male mice, with or without caloric restriction. Unlike the liver and eWAT, rhythmic clock genes in the BAT remained insensitive to feeding time, similar to the hypothalamus. We uncovered an internal split within the BAT in response to conflicting environmental cues, displaying inverted oscillations on a subset of metabolic genes without modifying its local core circadian machinery. Integrating tissue-specific responses on circadian transcriptional networks with metabolic outcomes may help elucidate the mechanism underlying the health burden of eating at unusual times.

摘要

在休息期间延长进食时间会扰乱外周和大脑的生物钟之间的相位关系,导致不良的健康影响。除了肝脏之外,代谢器官如何对定时低热量饮食做出反应在很大程度上还未被探索。我们研究了与肝脏和下丘脑相比,进食时间如何影响附睾白色和棕色脂肪组织(eWAT 和 BAT)中的生物钟基因表达。我们限制 C57BL/6J 雄性小鼠的食物摄入仅在白天或夜间进行,无论是否进行热量限制。与肝脏和 eWAT 不同,BAT 中的节律时钟基因对进食时间仍然不敏感,类似于下丘脑。我们发现 BAT 内部对冲突的环境线索存在分裂,在一组代谢基因上表现出相反的振荡,而不改变其局部核心生物钟机制。将组织特异性的生物钟转录网络反应与代谢结果相结合,可能有助于阐明在异常时间进食对健康的负担的机制。

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