Measurement of internal body time by blood metabolomics.
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 Linné's flower clock. In Linné'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.
Minami
Yoichi
Y
Laboratory for Systems Biology, RIKEN Center for Developmental Biology, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe, Hyogo 650-0047, Japan.
Kasukawa
Takeya
T
Kakazu
Yuji
Y
Iigo
Masayuki
M
Sugimoto
Masahiro
M
Ikeda
Satsuki
S
Yasui
Akira
A
van der Horst
Gijsbertus T J
GT
Soga
Tomoyoshi
T
Ueda
Hiroki R
HR
D000818:Animals; D001683:Biological Clocks; D001769:Blood / Q000378:metabolism*; D002853:Chromatography, Liquid; D002940:Circadian Rhythm; D005260:Female; D020179:Jet Lag Syndrome / Q000097:blood / Q000503:physiopathology; D008297:Male; D013058:Mass Spectrometry; D051379:Mice; D008808:Mice, Inbred CBA