Department of Physiology and Pharmacology, School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
Am J Physiol Gastrointest Liver Physiol. 2010 Nov;299(5):G1045-53. doi: 10.1152/ajpgi.00330.2010. Epub 2010 Sep 16.
Although the circadian liver clock is entrained by the feeding cycle, factors such as food volume and starvation interval are poorly understood. Per2::Luc knock-in mice were given two meals per day with different food volume sizes and/or with different intervals of starvation between two mealtimes with the total food volume per day fixed at 3.6 g (80 food pellets, ∼75% of free feeding) per mouse. The bioluminescence rhythm in the liver produced a unimodal peak but not bimodal peak under the regimen of two meals per day over 14-15 days. Peak Per2 expression occurred concurrently with the mealtime of the larger food volume, when the first and second meal were given as different food volume ratios under a 12 h feeding interval. When an equal volume of food was given under different starvation interval (8 h:16 h), the peak of the Per2 rhythm was close to peak by mealtime after long starvation (16 h). When food volumes for each mealtime were changed under 8 h:16 h, the peak rhythm was influenced by combined factors of food volume and starvation interval. Food intake after the 16-h starvation caused a significant increase in liver Per2, Dec1, and Bmal1 gene expression compared with food intake after the 8-h starvation with 8 h:16 h feeding intervals. In conclusion, the present results clearly demonstrate that food-induced entrainment of the liver clock is dependent on both food volume and the starvation interval between two meals. Therefore, normal feeding habits may help to maintain normal clock function in the liver organ.
尽管昼夜节律肝脏时钟受进食周期的影响,但食物量和饥饿间隔等因素仍知之甚少。Per2::Luc 敲入小鼠每天分两餐,每餐食物量不同,或两餐之间的饥饿间隔不同,但每天的总食物量固定为每只小鼠 3.6 克(80 个食物丸,约为自由喂养量的 75%)。在每天两餐的方案下,经过 14-15 天,肝脏中的生物发光节律呈单峰而非双峰。当第一餐和第二餐的食物量比例不同,且两餐之间的进食间隔为 12 小时时,较大食物量的用餐时间与 Per2 表达的峰值同时出现。当在不同的饥饿间隔(8 h:16 h)下给予等量的食物时,长时间饥饿(16 h)后的用餐时间附近接近 Per2 节律的峰值。当每餐的食物量在 8 h:16 h 下变化时,峰值节律受到食物量和饥饿间隔的综合因素的影响。与 8 h:16 h 的进食间隔相比,16 h 饥饿后的食物摄入会导致肝脏 Per2、Dec1 和 Bmal1 基因表达显著增加。总之,本研究结果清楚地表明,食物诱导的肝脏时钟同步依赖于食物量和两餐之间的饥饿间隔。因此,正常的饮食习惯可能有助于维持肝脏器官的正常时钟功能。