Two-meal caloric restriction induces 12-hour rhythms and improves glucose homeostasis.
Two-meal caloric restriction induces 12-hour rhythms and improves glucose homeostasis.
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DOI：
10.1096/fj.202002470r
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Kondratov RV
中科院分区：
文献类型：
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作者：
Velingkaar N;Mezhnina V;Poe A;Kondratov RV
葡萄糖代谢受到严格调节，破坏葡萄糖稳态是许多疾病的标志。热量限制（CR）、周期性禁食和昼夜节律与葡萄糖代谢相关。在这里，我们直接调查了CR是否依赖于周期性禁食和昼夜节律来改善葡萄糖代谢。CR实施为每天两餐（2 M-CR），间隔12小时，并与每天一餐CR、餐时（MT）和随意（AL）喂养进行比较。2 M-CR影响血糖、代谢信号、生物钟和葡萄糖代谢基因表达的昼夜节律。2 M-CR显著降低了全天候血糖，改善了葡萄糖耐量。在AL、MT和CR下观察到的mTOR信号传导和基因表达的24小时节律在2 M-CR中变为12小时节律。在禁食小鼠中，行为、基因表达和信号传导的12小时节律持续存在，这涉及一些内部调节。该研究强调，减少热量摄入而不是进食频率和禁食时间对于代谢重新编程和改善葡萄糖代谢至关重要，并提供了食物夹带分子起搏器的证据，该分子起搏器可以与光夹带的昼夜节律和节律解耦。
Glucose metabolism is tightly regulated and disrupting glucose homeostasis is a hallmark of many diseases. Caloric restriction (CR), periodic fasting, and circadian rhythms are interlinked with glucose metabolism. Here, we directly investigated if CR depends on periodic fasting and circadian rhythms to improve glucose metabolism. CR was implemented as two‐meals per day (2M‐CR), provided at 12‐hour intervals, and compared with one meal per day CR, mealtime (MT), and ad libitum (AL) feeding. The 2M‐CR impacted the circadian rhythms in blood glucose, metabolic signaling, circadian clock, and glucose metabolism gene expression. 2M‐CR significantly reduced around the clock blood glucose and improved glucose tolerance. Twenty‐four‐hour rhythms in mTOR signaling and gene expression observed under AL, MT, and CR, became 12‐hour rhythms in 2M‐CR. The 12‐hour rhythms in behavior, gene expression, and signaling persisted in fasted mice, implicating some internal regulation. The study highlights that the reduction in caloric intake rather than meal frequency and duration of fasting is essential for metabolic reprograming and improvement in glucose metabolism and provides evidence on food‐entrained molecular pacemaker, which can be uncoupled from the light‐entrained circadian clock and rhythms.