Skip to main content
SpringerLink
Log in
Book cover

Epigenetic Methods in Neuroscience Research pp 245–254Cite as

Metabolites as Clock Hands: Estimation of Internal Body Time Using Blood Metabolomics

  • Protocol

  • 1180 Accesses

Part of the book series: Neuromethods ((NM,volume 105))

Abstract

The circadian clock governs body time and regulates many physiological functions including sleep and wake cycles, body temperature, feeding, and hormone secretion. Alignment of drug dosing time to body time can maximize the pharmacological effect and minimize untoward effects. Therefore, a simple and robust method for estimating body time is important for drug efficacy or “chronotherapy”. We previously reported that a metabolite timetable could estimate body time with good accuracy. A metabolite timetable was constructed by profiling metabolites in human and mouse with capillary electrophoresis-mass spectrometry (CE-MS) and liquid chromatography–mass spectrometry (LC-MS). In this chapter, we describe practical methods to profile and identify oscillating metabolites.

This is a preview of subscription content, log in via an institution.

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   89.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   119.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Mohawk JA, Green CB, Takahashi JS (2012) Central and peripheral circadian clocks in mammals. Annu Rev Neurosci 35:445–462

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Reppert SM, Weaver DR (2002) Coordination of circadian timing in mammals. Nature 418:935–941

    Article  CAS  PubMed  Google Scholar 

  3. Ueda HR (2007) Systems biology of mammalian circadian clocks. Cold Spring Harb Symp Quant Biol 72:365–380

    Article  CAS  PubMed  Google Scholar 

  4. Takahashi JS, Hong H-K, Ko CH et al (2008) The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet 9:764–775

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  5. Minami Y, Kasukawa T, Kakazu Y et al (2009) Measurement of internal body time by blood metabolomics. Proc Natl Acad Sci U S A 106:9890–9895

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  6. Eckel-Mahan KL, Patel VR, Mohney RP et al (2012) Coordination of the transcriptome and metabolome by the circadian clock. Proc Natl Acad Sci U S A 109:5541–5546

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Dallmann R, Viola AU, Tarokh L et al (2012) The human circadian metabolome. Proc Natl Acad Sci U S A 109:2625–2629

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Weitzman ED, Fukushima D, Nogeire C et al (1971) Twenty-four hour pattern of the episodic secretion of cortisol in normal subjects. J Clin Endocrinol Metab 33:14–22

    Article  CAS  PubMed  Google Scholar 

  9. Kennaway DJ, Voultsios A, Varcoe TJ et al (2002) Melatonin in mice: rhythms, response to light, adrenergic stimulation, and metabolism. Am J Physiol Regul Integr Comp Physiol 282:R358–R365

    Article  CAS  PubMed  Google Scholar 

  10. Fustin J-MM, Doi M, Yamada H et al (2012) Rhythmic nucleotide synthesis in the liver: temporal segregation of metabolites. Cell Rep 1:341–349

    Article  CAS  PubMed  Google Scholar 

  11. Halberg F (1969) Chronobiology. Annu Rev Physiol 31:675–725

    Article  CAS  PubMed  Google Scholar 

  12. Reinberg A, Smolensky M, Levi F (1983) Aspects of clinical chronopharmacology. Cephalalgia 3(Suppl 1):69–78

    PubMed  Google Scholar 

  13. Reinberg A, Halberg F (1971) Circadian chronopharmacology. Annu Rev Pharmacol 11:455–492

    Article  CAS  PubMed  Google Scholar 

  14. Bocci V (1985) Administration of interferon at night may increase its therapeutic index. Cancer Drug Deliv 2:313–318

    Article  CAS  PubMed  Google Scholar 

  15. Labrecque G, Bélanger PM (1991) Biological rhythms in the absorption, distribution, metabolism and excretion of drugs. Pharmacol Ther 52:95–107

    Article  CAS  PubMed  Google Scholar 

  16. Lemmer B, Scheidel B, Behne S (1991) Chronopharmacokinetics and chronopharmacodynamics of cardiovascular active drugs. Propranolol, organic nitrates, nifedipine. Ann N Y Acad Sci 618:166–181

    Article  PubMed  Google Scholar 

  17. Ohdo S, Koyanagi S, Suyama H et al (2001) Changing the dosing schedule minimizes the disruptive effects of interferon on clock function. Nat Med 7:356–360

    Article  CAS  PubMed  Google Scholar 

  18. Hrushesky WJ (1985) Circadian timing of cancer chemotherapy. Science 228:73–75

    Article  CAS  PubMed  Google Scholar 

  19. Hasan S, Santhi N, Lazar AS et al (2012) Assessment of circadian rhythms in humans: comparison of real-time fibroblast reporter imaging with plasma melatonin. FASEB J 26:2414–2423

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Smith MR, Eastman CI (2008) Night shift performance is improved by a compromise circadian phase position: study 3. Circadian phase after 7 night shifts with an intervening weekend off. Sleep 31:1639–1645

    PubMed Central  PubMed  Google Scholar 

  21. Wright KP, Gronfier C, Duffy JF et al (2005) Intrinsic period and light intensity determine the phase relationship between melatonin and sleep in humans. J Biol Rhythms 20:168–177

    Article  PubMed Central  PubMed  Google Scholar 

  22. Horowitz TS, Cade BE, Wolfe JM et al (2001) Efficacy of bright light and sleep/darkness scheduling in alleviating circadian maladaptation to night work. Am J Physiol Endocrinol Metab 281:E384–E391

    CAS  PubMed  Google Scholar 

  23. Kasukawa T, Sugimoto M, Hida A et al (2012) Human blood metabolite timetable indicates internal body time. Proc Natl Acad Sci U S A 109:15036–15041

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Hirayama A, Kami K, Sugimoto M et al (2009) Quantitative metabolome profiling of colon and stomach cancer microenvironment by capillary electrophoresis time-of-flight mass spectrometry. Cancer Res 69:4918

    Article  CAS  PubMed  Google Scholar 

  25. Ishii N, Nakahigashi K, Baba T et al (2007) Multiple high-throughput analyses monitor the response of E. coli to perturbations. Science 316:593–597

    Article  CAS  PubMed  Google Scholar 

  26. Timm S, Florian A, Wittmiß M et al (2013) Serine acts as metabolic signal for the transcriptional control of photorespiration-related genes in Arabidopsis thaliana. Plant Physiol 162:379–389

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  27. Sugimoto M, Wong DT, Hirayama A et al (2010) Capillary electrophoresis mass spectrometry-based saliva metabolomics identified oral, breast and pancreatic cancer-specific profiles. Metabolomics 6:78–95

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  28. Tsang S, Sun Z, Luke B et al (2005) A comprehensive SNP-based genetic analysis of inbred mouse strains. Mamm Genome 16:476–480

    Article  CAS  PubMed  Google Scholar 

  29. Moriya T, Yoshinobu Y, Ikeda M et al (1998) Potentiating action of MKC-242, a selective 5-HT1A receptor agonist, on the photic entrainment of the circadian activity rhythm in hamsters. Br J Pharmacol 125:1281–1287

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  30. Soga T, Ohashi Y, Ueno Y et al (2003) Quantitative metabolome analysis using capillary electrophoresis mass spectrometry research articles. J Proteome Res 2:488–494

    Article  CAS  PubMed  Google Scholar 

  31. Soga T, Baran R, Suematsu M et al (2006) Differential metabolomics reveals ophthalmic acid as an oxidative stress biomarker indicating hepatic glutathione consumption. J Biol Chem 281:16768–16776

    Article  CAS  PubMed  Google Scholar 

  32. Soga T, Heiger DN (2000) Amino acid analysis by capillary electrophoresis electrospray ionization mass spectrometry. Anal Chem 72:1236–1241

    Article  CAS  PubMed  Google Scholar 

  33. Baran R, Kochi H, Saito N et al (2006) MathDAMP: a package for differential analysis of metabolite profiles. BMC Bioinform 7:530

    Article  Google Scholar 

  34. Saito K, Maekawa K, Pappan KL et al (2013) Differences in metabolite profiles between blood matrices, ages, and sexes among Caucasian individuals and their inter-individual variations. Metabolomics 10:402–413

    Article  Google Scholar 

  35. Ishikawa M, Maekawa K, Saito K et al (2014) Plasma and serum lipidomics of healthy white adults shows characteristic profiles by subjects’ gender and age. PLoS One 9:e91806

    Article  PubMed Central  PubMed  Google Scholar 

  36. Froy O, Miskin R (2007) The interrelations among feeding, circadian rhythms and ageing. Prog Neurobiol 82:142–150

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory for Synthetic Biology, Quantitative Biology Center, RIKEN, 1-3, Yamadaoka, Suita, Osaka, 565-0871, Japan

    Hitoshi Iuchi, Rikuhiro G. Yamada & Hiroki R. Ueda

  2. Systems Biology Program, Graduate School of Media and Governance, Keio University, Fujisawa, 252-8520, Japan

    Hitoshi Iuchi

  3. Department of Systems Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1, Bunkyo-ku, Tokyo, 113-0033, Japan

    Hiroki R. Ueda

Authors
  1. Hitoshi Iuchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rikuhiro G. Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hiroki R. Ueda
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hiroki R. Ueda .

Editor information

Editors and Affiliations

  1. Neuroscience Center, University of Helsinki, Helsinki, Finland

    Nina Karpova

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer Science+Business Media New York

About this protocol

Cite this protocol

Iuchi, H., Yamada, R.G., Ueda, H.R. (2016). Metabolites as Clock Hands: Estimation of Internal Body Time Using Blood Metabolomics. In: Karpova, N. (eds) Epigenetic Methods in Neuroscience Research. Neuromethods, vol 105. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-2754-8_15

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-2754-8_15

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-2753-1

  • Online ISBN: 978-1-4939-2754-8

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation