The dynamic range of the human metabolome revealed by challenges

KrugS.; KastenmüllerG.; StücklerF.RistM.J.SkurkT.SailerM.RafflerJ.R?misch-MarglW.AdamskiJ.PrehnC.FrankT.EngelK.-H.HofmannT.LuyB.ZimmermannR.MoritzF.Schmitt-KopplinP.KrumsiekJ.KremerW.HuberF.OehU.TheisF.J.SzymczakW.HaunerH.SuhreK.DanielH.

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The dynamic range of the human metabolome revealed by challenges

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Metabolic challenge protocols, such as the oral glucose tolerance test, can uncover early alterations in metabolism preceding chronic diseases. Nevertheless, most metabolomics data accessible today reflect the fasting state. To analyze the dynamics of the human metabolome in response to environmental stimuli, we submitted 15 young healthy male volunteers to a highly controlled 4 d challenge protocol, including 36 h fasting, oral glucose and lipid tests, liquid test meals, physical exercise, and cold stress. Blood, urine, exhaled air, and breath condensate samples were analyzed on up to 56 time points by MS- and NMR-based methods, yielding 275 metabolic traits with a focus on lipids and amino acids. Here, we show that physiological challenges increased interindividual variation even in phenotypically similar volunteers, revealing metabotypes not observable in baseline metabolite profiles; volunteer-specific metabolite concentrations were consistently reflected in various biofluids; and readouts from a systematic model of β-oxidation (e.g., acetylcarnitine/ palmitylcarnitine ratio) showed significant and stronger associations with physiological parameters (e.g., fat mass) than absolute metabolite concentrations, indicating that systematic models may aid in understanding individual challenge responses. Due to the multitude of analytical methods, challenges and sample types, our freely available metabolomics data set provides a unique reference for future metabolomics studies and for verification of systems biology models.

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《The FASEB Journal》 |2012年第6期|2607-2619|共13页
作者
KrugS.; KastenmüllerG.; StücklerF.RistM.J.SkurkT.SailerM.RafflerJ.R?misch-MarglW.AdamskiJ.PrehnC.FrankT.EngelK.-H.HofmannT.LuyB.ZimmermannR.MoritzF.Schmitt-KopplinP.KrumsiekJ.KremerW.HuberF.OehU.TheisF.J.SzymczakW.HaunerH.SuhreK.DanielH.;
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Molecular Nutrition Unit, Technische Universit?t München, Freising-Weihenstephan, Germany;

Department of Nutritional Medicine, Research Center for Nutrition and Food Sciences, Technische;

Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München, Neuherberg, GermanyMedical Radiation Physics and Diagnostics Research Unit, Helmholtz Zentrum München, NeuherbergInstitute of Experimental Genetics, Genome Analysis Center, Helmholtz Zentrum München, NeuherbergDepartment of General Food Technology, Technische Universit?t München, Freising-WeihenstephanInstitute of Organic Chemistry, Karlsruhe Institute of Technology (KIT), Karlsruhe, GermanyComprehensive Molecular Analytics Cooperation Group, Joint Mass Spectrometry Centre, HelmholtzAnalytical Biogeochemistry Research Unit, Helmholtz Zentrum München, Neuherberg, GermanyLipoFIT Analytic GmbH, Regensburg, Germany, Institute of Biophysics and Physical BiochemistryLipoFIT Analytic GmbH, Regensburg, GermanyDepartment of Food Chemistry and Molecular Sensory Science, Technische Universit?t München;

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正文语种英语
中图分类生物化学;
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Clinical study; Human physiology; Nutrition; Systems biology; Time-resolved fingerprinting;

The dynamic range of the human metabolome revealed by challenges

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