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 °C, and all mice died at 18 °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.

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) 具有作为预防或治疗许多疾病的方法的潜力。TRF 的潜在副作用仍然未知。在这里，我们表明每天对小鼠进行 4 小时 TRF 治疗会严重损害体温稳态并可能导致死亡。将近一半的小鼠在 21°C 下死亡，所有小鼠在 4 小时 TRF 期间都在 18°C 下死亡。这种效应受生物钟调节，并与由于体温稳态丧失导致的严重体温过低有关。值得注意的是，在 TRF 期间，通过 SCN 病变或持续光照来破坏生物钟可以挽救致死率。Ccr5和Calcrl，它们参与体温调节。总之，我们的结果证明了 TRF 对体温稳态的有效影响以及 SCN 功能在该过程中的作用。我们的结果进一步表明，昼夜节律失常在某些压力条件下可能具有潜在的有益影响。