Impaired function of the suprachiasmatic nucleus rescues the loss of body temperature homeostasis caused by time-restricted feeding  

损毁视交叉神经上核挽救了时间限制性饮食导致的小鼠致死

作　　者：Zhihui Zhang Qiaocheng Zhai Yue Gu Tao Zhang Zhengyun Huang Zhiwei Liu Yi Liu Ying Xu 张志辉;翟巧成;顾越;张陶;黄正云;刘志玮;刘一;徐璎(Model Animal Research Center,Nanjing University,Nanjing 210061,China;Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda Genomic Resource Center,Soochow University,Suzhou 215123,China;Department of Physiology,University of Texas Southwestern Medical Center,Dallas,TX 75390,USA;State Key Laboratory of Radiation Medicine and Protection,Soochow University,Suzhou 215123,China)

机构地区：[1]Model Animal Research Center,Nanjing University,Nanjing 210061,China [2]Jiangsu Key Laboratory of Neuropsychiatric Diseases and Cambridge-Suda Genomic Resource Center,Soochow University,Suzhou 215123,China [3]Department of Physiology,University of Texas Southwestern Medical Center,Dallas,TX 75390,USA [4]State Key Laboratory of Radiation Medicine and Protection,Soochow University,Suzhou 215123,China

出　　处：《Science Bulletin》2020年第15期1268-1280,M0003,M0004,共15页科学通报（英文版）

基　　金：supported by the National Natural Science Foundation of China(31630091,3123004931600958);Royal SocietyNewton Advance Fellowship(NA150373);Ministry of Science and Technology(YFA0801100)to YX;National Institutes of Health(1R35GM118118);Cancer Prevention and Research Institute of Texas(RP160268);Welch Foundation(I-1560)to YL;Priority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD);National Center for International Research(2017B01012)。

摘　　要：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℃,and all mice died at 18℃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.视交叉神经上核(SCN)是哺乳动物生物钟的神经中枢系统,通过偶联身体周围组织器官调控生理代谢、睡眠、免疫和体温等节律性的生理过程,使哺乳动物更好地适应节律性变化的环境并生存.时间限制性饮食(TRF)已被证明对人的健康大有益处,是一种潜在的预防和治疗许多疾病的方法.本文发现每天4 h的TRF会损害小鼠的体温稳态平衡,环境温度的降低会加剧这一效应并导致小鼠死亡,且这种效应受到生物钟的调控.通过SCN损伤或非创伤性地干扰生物钟,改善了小鼠的体温稳态使其存活.进一步通过RNA-Seq检测,发现TRF影响背内侧下丘脑(DMH)基因组的稳定性和节律性基因的表达,抑制参与体温调节基因Ccr5,Calcrl等的表达.结果表明,TRF对体温稳态有潜在的作用,而扰乱生物钟中枢神经系统SCN在生命体应对一些应激条件下可能产生有益的影响.

关 键 词：Time-restricted feeding Body temperature HYPOTHERMIA Circadian clock The suprachiasmatic nucleus The dorsomedial hypothalamus 

分 类 号：R338[医药卫生—人体生理学]