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 poten...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.展开更多
基金supported by the National Natural Science Foundation of China(31630091,3123004931600958)Royal SocietyNewton Advance Fellowship(NA150373)+5 种基金Ministry of Science and Technology(YFA0801100)to YXNational Institutes of Health(1R35GM118118)Cancer Prevention and Research Institute of Texas(RP160268)Welch Foundation(I-1560)to YLPriority Academic Program Development of the Jiangsu Higher Education Institutes(PAPD)National Center for International Research(2017B01012)。
文摘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.
