Food Entrainment of the Human Circadian Timing System

大多数生物体内都有生物钟来调节许多关键生物功能（如激素分泌、睡眠时间、新陈代谢）的昼夜节律。包括人类在内的哺乳动物的昼夜节律系统由一个位于大脑下丘脑的“主”时钟和遍布全身的许多“外围”时钟组成。越来越多的证据表明，这些生物钟的异常计时会导致正常生物学的缺陷。这种异常时间的影响可能是短暂的（如时差反应），也可能持续数年（如倒班工人）。在第二种情况下，非正常节律的长期影响被认为是许多工业事故的一个致病因素，并可能导致心脏病和代谢性疾病等主要疾病的发病率增加。为了使我们的内部时钟与外部环境的变化相匹配，它们与各种环境时间线索同步。虽然已知光是大脑中“主”时钟的主要同步器，但对外围时钟的同步却知之甚少。来自动物研究的证据表明，进食时间是外周时钟的重要信号。然而，这些动物实验还没有在人类身上进行，因为；1)世界上很少有地方可以进行控制良好的人类昼夜节律实验，2)很难获得除血液以外的多种人体组织样本。在萨里大学，我们拥有优秀的人类生物学设施、昼夜节律专家和营养科学专家。此外，在我们最近的研究中，我们优化了一种从人类志愿者身上提取多种脂肪样本的方法。因此，我们建议进行一组极其重要和及时的实验，以发现喂食时间是否可以调节人体时钟。这项工作的结果将对科学家和公众产生重要影响。科学家们将了解到有关生物钟基本生物学的重要新信息。如果发现食物能够调节昼夜节律，那么这将确定新的治疗策略，可能导致新的饮食干预措施，以减轻轮班工作和时差对健康和表现的负担。近年来，公众和媒体对生物钟和营养都很感兴趣，因此这项研究可能会引起广泛的兴趣。我们尤其希望发现新的科学发现，为包括航空旅客、轮班工人和全盲者在内的昼夜节律紊乱患者提供非药物治疗的基础。

Most living organisms possess internal clocks that regulate daily (circadian) rhythms in many key biological functions (e.g. hormone secretion, sleep time, metabolism). The circadian timing system in mammals, including humans, consists of a 'master' clock within a part of the brain called the hypothalamus and many 'peripheral' clocks found throughout the body. There is increasing evidence to show that abnormal timing of these clocks leads to defects in normal biology. The effects of this abnormal timing can be short lived (e.g. in jet lag) or present over a number of years (e.g. in shift workers). In the second scenario, the long term effects of abnormal rhythms is thought to be a causative factor in many industrial accidents and can lead to increased incidence of major contributors to ill health, such as heart and metabolic diseases. In order for our internal clocks to be matched to external changes in the environment, they are synchronised by various environmental time cues. Although it is known that light is the main synchroniser of the 'master' clock in the brain, the synchronisation of peripheral clocks is poorly understood. Evidence from animal studies suggests that the time of feeding is an important signal for peripheral clocks. However, these animal experiments have not been performed in humans because; 1) very few places in the world can perform well controlled human circadian experiments, and 2) it is difficult to obtain multiple samples of human tissue other than blood. At the University of Surrey, we have the benefit of excellent human biology facilities, experts in circadian rhythms, and experts in nutritional science. Moreover, in our recent research, we have optimised a method for taking multiple samples of fat from human volunteers. We therefore propose to conduct a set of extremely important and timely experiments to discover whether the time of feeding can regulate human clocks. The results of the work will have important implications for scientists and the public. Scientists will learn crucial new information about the basic biology of body clocks. If food is found to be able to regulate circadian timing then this would identify novel treatment strategies that may lead to novel dietary interventions to reduce the burden of shift work and jet lag on health and performance. There has been a lot of public and media interest in both body clocks and nutrition over recent years and so this research is likely to be of broad interest. In particular, we hope to discover new scientific findings that will underpin non-drug treatment for sufferers of circadian disorders including air travellers, shift workers and the totally blind.