PMID- 33543540 OWN - NLM STAT- MEDLINE DCOM- 20210624 LR - 20221005 IS - 1530-6860 (Electronic) IS - 0892-6638 (Print) IS - 0892-6638 (Linking) VI - 35 IP - 2 DP - 2021 Feb TI - Two-meal caloric restriction induces 12-hour rhythms and improves glucose homeostasis. PG - e21342 LID - 10.1096/fj.202002470R [doi] LID - e21342 AB - 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. CI - (c) 2021 The Authors. The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology. FAU - Velingkaar, Nikkhil AU - Velingkaar N AD - Center for Gene Regulation in Health and Disease and Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH, USA. FAU - Mezhnina, Volha AU - Mezhnina V AD - Center for Gene Regulation in Health and Disease and Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH, USA. FAU - Poe, Allan AU - Poe A AD - Center for Gene Regulation in Health and Disease and Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH, USA. FAU - Kondratov, Roman V AU - Kondratov RV AD - Center for Gene Regulation in Health and Disease and Department of Biological Geological and Environmental Sciences, Cleveland State University, Cleveland, OH, USA. LA - eng GR - R01 AG039547/AG/NIA NIH HHS/United States GR - S10 OD025252/OD/NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - FASEB J JT - FASEB journal : official publication of the Federation of American Societies for Experimental Biology JID - 8804484 RN - EC 2.7.11.1 (TOR Serine-Threonine Kinases) RN - IY9XDZ35W2 (Glucose) SB - IM MH - Animals MH - Caloric Restriction/*methods MH - *Circadian Rhythm MH - Fasting/metabolism MH - Glucose/*metabolism MH - *Homeostasis MH - Male MH - Meals MH - Mice MH - Mice, Inbred C57BL MH - Signal Transduction MH - TOR Serine-Threonine Kinases/metabolism PMC - PMC7898832 OTO - NOTNLM OT - 12-hour rhythms OT - aging OT - circadian rhythms OT - diet OT - gene expression OT - glucose homeostasis OT - metabolism COIS- None declared. EDAT- 2021/02/06 06:00 MHDA- 2021/06/25 06:00 PMCR- 2021/02/22 CRDT- 2021/02/05 06:07 PHST- 2020/11/11 00:00 [received] PHST- 2020/12/10 00:00 [revised] PHST- 2020/12/21 00:00 [accepted] PHST- 2021/02/05 06:07 [entrez] PHST- 2021/02/06 06:00 [pubmed] PHST- 2021/06/25 06:00 [medline] PHST- 2021/02/22 00:00 [pmc-release] AID - FSB221342 [pii] AID - 10.1096/fj.202002470R [doi] PST - ppublish SO - FASEB J. 2021 Feb;35(2):e21342. doi: 10.1096/fj.202002470R.