Measurement of internal body time by blood metabolomics
Measurement of internal body time by blood metabolomics
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DOI：
10.1073/pnas.0900617106
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发表时间：
2009-06-16
影响因子：
11.1
通讯作者：
Ueda, Hiroki R.
中科院分区：
文献类型：
--
作者：
Minami, Yoichi;Kasukawa, Takeya;Ueda, Hiroki R.
通过几个时间点测定法检测体内时间（BT）一直是医学领域的一个长期挑战，因为BT信息可以在给药过程中最大化效力和最小化毒性，从而实现高度优化的药物治疗。为了应对这一挑战，我们之前开发了“分子时间表方法”的概念，其最初的灵感来自Linne的花钟。在Linne的花钟中，人们可以通过观察各种花的开放和关闭模式来估计一天的时间。同样，在分子时间表方法中，人们可以通过分析分子时间表中物质的上升和下降模式来测量一天的BT。为了使这种方法在临床上可行，我们现在进行了血液代谢组分析，并在这里报告了小鼠血浆中数百种生物钟控制代谢物的成功定量。基于昼夜血液代谢组学，我们可以检测不同条件下的个体BT，证明其对遗传背景、性别、年龄和喂养差异的稳健性。这种方法的力量也被证明是灵敏和准确地检测昼夜节律紊乱的时差小鼠。这些结果提示基于代谢组学的BT检测（“代谢物时间表方法”）的潜力，这将导致时间疗法和个性化医疗的实现。
Detection of internal body time (BT) via a few-time-point assay has been a longstanding challenge in medicine, because BT information can be exploited to maximize potency and minimize toxicity during drug administration and thus will enable highly optimized medication. To address this challenge, we previously developed the concept, "molecular-timetable method,'' which was originally inspired by Linne's flower clock. In Linne's flower clock, one can estimate the time of the day by watching the opening and closing pattern of various flowers. Similarly, in the molecular-timetable method, one can measure the BT of the day by profiling the up and down patterns of substances in the molecular timetable. To make this method clinically feasible, we now performed blood metabolome analysis and here report the successful quantification of hundreds of clock-controlled metabolites in mouse plasma. Based on circadian blood metabolomics, we can detect individual BT under various conditions, demonstrating its robustness against genetic background, sex, age, and feeding differences. The power of this method is also demonstrated by the sensitive and accurate detection of circadian rhythm disorder in jet-lagged mice. These results suggest the potential for metabolomics-based detection of BT ("metabolite-timetable method''), which will lead to the realization of chronotherapy and personalized medicine.