Departments of Neurohumoral Regulations, Institute of Physiology v.v.i., Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Chronobiol Int. 2011 Apr;28(3):204-15. doi: 10.3109/07420528.2010.548615.
Physiological functions of the gastrointestinal tract (GIT) are temporally controlled such that they exhibit circadian rhythms. The circadian rhythms are synchronized with the environmental light-dark cycle via signaling from the central circadian clock located in the suprachiasmatic nucleus (SCN) of the hypothalamus, and by food intake. The aim of the study was to determine the extent to which disturbance in the SCN signaling via prolonged exposure to constant light affects circadian rhythms in the liver, duodenum, and colon, as well as to determine whether and to what extent food intake can restore rhythmicity in individual parts of the GIT. Adult male rats were maintained in constant light (LL) for 30 days and fed ad libitum throughout the entire interval or exposed to a restricted feeding (RF) regime for the last 14 days in LL. Locomotor and feeding behaviors were recorded throughout the experiment. On the 30th day, daily expression profiles of clock genes (Per1, Per2, Rev-erbα, and Bmal1) and of clock-controlled genes (Wee1 and Dbp) were measured by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in the duodenum, colon, and liver. By the end of the LL exposure, rats fed ad libitum had completely lost their circadian rhythms in activity and food intake. Daily expression profiles of clock genes and clock-controlled genes in the GIT were impaired to an extent depending on the tissue and gene studied, but not completely abolished. In the liver and colon, exposure to LL abolished circadian rhythms in expression of Per1, Per2, Bmal1, and Wee1, whereas it impaired, but preserved, rhythms in expression of Rev-erbα and Dbp. In the duodenum, all but Wee1 expression rhythms were preserved. Restricted feeding restored the rhythms to a degree that varied with the tissue and gene studied. Whereas in the liver and duodenum the profiles of all clock genes and clock-controlled genes became rhythmic, in the colon only Per1, Bmal1, and Rev-erbα-but not Per2, Wee1, and Dbp-were expressed rhythmically. The data demonstrate a greater persistence of the rhythmicity of the circadian clocks in the duodenum compared with that in the liver and colon under conditions when signaling from the SCN is disrupted. Moreover, disrupted rhythmicity may be restored more effectively by a feeding regime in the duodenum and liver compared to the colon.
胃肠道(GIT)的生理功能是随时间控制的,表现出昼夜节律。昼夜节律通过来自下丘脑视交叉上核(SCN)的中央生物钟的信号以及食物摄入与环境的明暗循环同步。本研究的目的是确定通过长时间暴露于恒定光来干扰 SCN 信号对肝脏、十二指肠和结肠的昼夜节律的影响程度,以及确定食物摄入是否以及在何种程度上可以恢复 GIT 各个部分的节律性。成年雄性大鼠在恒定光照(LL)下维持 30 天,并在整个期间自由进食,或在 LL 下的最后 14 天暴露于限时进食(RF)方案。在整个实验过程中记录运动和进食行为。在第 30 天,通过实时逆转录聚合酶链反应(RT-PCR)测量十二指肠、结肠和肝脏中时钟基因(Per1、Per2、Rev-erbα 和 Bmal1)和时钟控制基因(Wee1 和 Dbp)的每日表达谱。在 LL 暴露结束时,自由进食的大鼠完全失去了活动和食物摄入的昼夜节律。根据组织和基因研究,GIT 中时钟基因和时钟控制基因的每日表达谱受到不同程度的损害,但并未完全消除。在肝脏和结肠中,LL 暴露消除了 Per1、Per2、Bmal1 和 Wee1 的表达节律,而 Rev-erbα 和 Dbp 的表达节律受损但仍保留。在十二指肠中,除了 Wee1 表达节律外,其他节律均保留。限时进食在一定程度上恢复了节律,这种恢复程度因组织和基因研究而异。在肝脏和十二指肠中,所有时钟基因和时钟控制基因的表达谱均呈节律性,而在结肠中仅 Per1、Bmal1 和 Rev-erbα 具有节律性表达,而 Per2、Wee1 和 Dbp 则无节律性表达。数据表明,在 SCN 信号受到干扰的情况下,十二指肠中昼夜节律钟的节律性比肝脏和结肠中更持久。此外,与结肠相比,通过进食方案可以更有效地恢复十二指肠和肝脏中昼夜节律的节律性。