Center for Gene Regulation in Health and Disease and Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH, USA.
FASEB J. 2021 Feb;35(2):e21342. doi: 10.1096/fj.202002470R.
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.
葡萄糖代谢受到严格调控，破坏葡萄糖内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密切相关。在这里，我们直接研究了 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（2M-CR），每 12 小时提供一次，与每天一餐 CR、用餐时间（MT）和随意进食（AL）进行比较。2M-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。2M-CR 显著降低了全天的血糖水平并改善了葡萄糖耐量。在 AL、MT 和 CR 下观察到的 mTOR 信号和基因表达的 24 小时节律在 2M-CR 中变为 12 小时节律。在禁食小鼠中，行为、基因表达和信号的 12 小时节律仍然存在，这暗示了一些内部调节。该研究强调，减少热量摄入而不是进食频率和禁食时间长短对于代谢重编程和改善葡萄糖代谢至关重要，并提供了关于食物诱导的分子起搏器的证据，该起搏器可以与光诱导的生物钟和节律解耦。
