Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding
Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding
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视交叉上核功能受损可挽救因限时进食引起的体温稳态丧失
DOI：
10.1016/j.scib.2020.03.025
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发表时间：
2020-08-15
期刊：
影响因子：
18.9
通讯作者：
Xu, Ying
中科院分区：
文献类型：
--
作者：
Zhang, Zhihui;Zhai, Qiaocheng;Xu, Ying
视交叉上核（SCN）是驱动体温节律的主要昼夜节律起搏器。限时喂养（TRF）具有预防或治疗许多疾病的潜力。扶轮基金会潜在的副作用仍然未知。本研究表明，每天4小时的TRF治疗会严重损害小鼠的体温稳态，并可能导致死亡。在4小时的TRF中，近一半的小鼠在21℃时死亡，所有小鼠在18℃时死亡。这种效应受生物钟调节，并与体温稳态丧失引起的严重体温过低有关。值得注意的是，在TRF期间，通过SCN病变或恒定光照破坏生物钟可以挽救致死性。对下丘脑背内侧（DMH）昼夜节律基因表达的分析表明，TRF对DMH的节律转录组进行了重编程，并抑制了参与体温调节的基因（如Ccr5和Calcrl）的表达。总之，我们的研究结果证明了TRF对体温稳态的有效影响以及SCN功能在这一过程中的作用。我们的研究结果进一步表明，在某些应激条件下，昼夜节律性可能具有潜在的有益作用。(C) 2020中国科学出版社。由爱思唯尔、中国科学出版社联合出版。版权所有。
The suprachiasmatic nucleus (SCN) is the master circadian pacemaker that drives body temperature rhythm. Time-restricted feeding (TRF) has potential as a preventative or therapeutic approach against many diseases. The potential side effects of TRF remain unknown. Here we show that daily 4-h TRF treatment in mice can severely impair body temperature homeostasis and can result in lethality. Nearly half of the mice died at 21 degrees C, and all mice died at 18 degrees C during 4-h TRF. This effect was modulated by the circadian clock and was associated with severe hypothermia due to loss of body temperature homeostasis. Remarkably, disrupting the circadian clock by SCN lesions or constant light rescued lethality during TRF. Analysis of circadian gene expression in the dorsomedial hypothalamus (DMH) demonstrated that TRF reprograms rhythmic transcriptome in DMH and suppresses expression of genes, such as Ccr5 and Calcrl, which are involved in thermoregulation. Together, our results demonstrated a potent effect of TRF on body temperature homeostasis and the role of SCN function in this process. Our results further suggested that circadian arrhythmicity can have potential beneficial effects under certain stress conditions. (C) 2020 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.