Keeping Body Time By Metabolomics

With a well-tuned mechanism rivaling that of the finest Swiss timepiece, the human body clock regulates changes in gene expression that lead to temporal oscillations of hormone and metabolite levels. As a result, people's internal "body time" can influence the efficacy and side effects of therapeutic drugs they are taking. But developing individualized "chronotherapy" to optimize the benefits of medicines has been hindered so far by a lack of clinical methods to measure body time. Now, a Japan-based team led by Tomoyoshi Soga of Keio University and Hiroki R. Ueda of RIKEN's Center for Developmental Biology has comprehensively profiled mouse blood metabolites that oscillate with circadian rhythms (Proc. Natl. Acad. Sci. USA, DOI: 10.1073/pnas.0900617106). The researchers used LC/MS to quantify hundreds of clock-controlled metabolites in mouse blood plasma and to construct a molecular timetable for the production of these substances. With the metabolite timetable in hand, they estimated individual body times of mice kept under various light and dark conditions and were able to detect metabolite signatures for conditions that elicit jet lag in people. Besides aiding the development of tailored medication regimens for people, metabolite timetables might be used to diagnose circadian rhythm sleep disorders, the researchers suggest.