title: The circadian clock controls fluctuations of colonic cell proliferation during the light/dark cycle via feeding behavior in mice.
abstract: The mammalian circadian system is controlled not only by the suprachiasmatic nucleus (SCN), but also by the peripheral clocks located in tissues such as liver, kidney, small intestine, and colon, mediated through signals such as hormones. Peripheral clocks, but not the SCN, can be entrained by food intake schedules. While it is known that cell proliferation exhibits a circadian rhythm in the colon epithelium, it is unclear how this rhythm is influenced by food intake schedules. Here, we aimed to determine the relationships between feeding schedules and cell proliferation in the colon epithelium by means of immunochemical analysis, using 5-bromo-2'-deoxyuridine (BrdU), as well as to elucidate how feeding schedules influence the colonic expression of clock and cell cycle genes, using real-time reverse-transcription PCR (qRT-PCR). Cell proliferation in the colonic epithelium of normal mice exhibited a daily fluctuation, which was abrogated in Clock mutant mice. The day/night pattern of cellular proliferation and clock gene expression under daytime and nighttime restricted feeding (RF) schedules showed opposite tendencies. While daytime RF for every 4 h attenuated the day/night pattern of cell proliferation, this was restored to normal in the Clock mutant mice under the nighttime RF schedule. These results suggest that feeding schedules contribute to the establishment of a daily fluctuation of cell proliferation and RF can recover it in Clock mutant mice. Thus, this study demonstrates that the daily fluctuation of cell proliferation in the murine colon is controlled by a circadian feeding rhythm, suggesting that feeding schedules are important for rhythmicity in the proliferation of colon cells.
authors.affiliation: a Laboratory of Physiology and Pharmacology , School of Advanced Sciences and Engineering, Waseda University , Tokyo , Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yoshida
authors.affiliation: a Laboratory of Physiology and Pharmacology , School of Advanced Sciences and Engineering, Waseda University , Tokyo , Japan.
authors.forename: Natsumi
authors.initials: N
authors.lastname: Aoki
authors.affiliation: a Laboratory of Physiology and Pharmacology , School of Advanced Sciences and Engineering, Waseda University , Tokyo , Japan.
authors.forename: Mizuho
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: a Laboratory of Physiology and Pharmacology , School of Advanced Sciences and Engineering, Waseda University , Tokyo , Japan.
authors.forename: Shinya
authors.initials: S
authors.lastname: Aoyama
authors.affiliation: a Laboratory of Physiology and Pharmacology , School of Advanced Sciences and Engineering, Waseda University , Tokyo , Japan.
authors.forename: Shigenobu
authors.initials: S
authors.lastname: Shibata
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000502:physiology*; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics*; D004435:Eating / Q000235:genetics / Q000502:physiology*; D005247:Feeding Behavior / Q000502:physiology*; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000502:physiology; D056950:Period Circadian Proteins / Q000378:metabolism; D017440:Photoperiod; D013493:Suprachiasmatic Nucleus / Q000378:metabolism
chemical_list: D056950:Period Circadian Proteins
keywords: Cell cycle; circadian rhythm; colon; feeding; proliferation