The human circadian metabolome
The human circadian metabolome
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DOI：
10.1073/pnas.1114410109
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发表时间：
2012-02-14
影响因子：
11.1
通讯作者：
Brown, Steven A.
中科院分区：
文献类型：
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作者：
Dallmann, Robert;Viola, Antoine U.;Brown, Steven A.
生物钟协调着人类生理的许多方面，而生物钟的紊乱与各种病理有关，从癌症到代谢综合征和糖尿病。尽管有证据表明，新陈代谢和昼夜节律在转录水平上密切相关，但这些影响是直接受时钟控制，还是由休息-活动周期和食物摄入的时间调节，目前尚不清楚。为了回答这个问题，我们对受试者在一天中不同时间的血浆和唾液代谢组进行了无偏见的筛选。为了将间接影响降至最低，受试者被保持在40小时不变的常规状态中，包括强迫姿势、持续昏暗的光线、每小时一次的等卡路里饮食和睡眠剥夺。在这些条件下，我们发现血浆和唾液中约有15%的已鉴定代谢物处于昼夜节律控制之下，最显著的是血浆中的脂肪酸和唾液中的氨基酸。我们的数据表明，内源性生物钟对多条与睡眠或进食无关的人类代谢途径有很强的直接影响。此外，他们还确定了人体昼夜节律和睡眠压力的多个潜在小分子生物标记物。
The circadian clock orchestrates many aspects of human physiology, and disruption of this clock has been implicated in various pathologies, ranging from cancer to metabolic syndrome and diabetes. Although there is evidence that metabolism and the circadian clockwork are intimately linked on a transcriptional level, whether these effects are directly under clock control or are mediated by the rest-activity cycle and the timing of food intake is unclear. To answer this question, we conducted an unbiased screen in human subjects of the metabolome of blood plasma and saliva at different times of day. To minimize indirect effects, subjects were kept in a 40-h constant routine of enforced posture, constant dim light, hourly isocaloric meals, and sleep deprivation. Under these conditions, we found that similar to 15% of all identified metabolites in plasma and saliva were under circadian control, most notably fatty acids in plasma and amino acids in saliva. Our data suggest that there is a strong direct effect of the endogenous circadian clock on multiple human metabolic pathways that is independent of sleep or feeding. In addition, they identify multiple potential small-molecule biomarkers of human circadian phase and sleep pressure.