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The dynamic range of the human metabolome revealed by challenges
Abstract
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.—Krug, S., Kastenmüller, G., Stückler, F., Rist, M. J., Skurk, T., Sailer, M., Raffler, J., Römisch‐Margl, W., Adamski, J., Prehn, C., Frank, T., Engel, K‐H., Hofmann, T., Luy, B., Zimmermann, R., Moritz, F., Schmitt‐Kopplin, P., Krumsiek, J., Kremer, W., Huber, F., Oeh, U., Theis, F. J., Szymczak, W., Hauner, H., Suhre, K., Daniel, H. The dynamic range of the human metabolome revealed by challenges. FASEB J. 26, 2607‐2619 (2012). www.fasebj.org
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“This effect, however, may reflect mitochondrial metabolism under acute dietary challenge (48) rather than effects of long-term habitual diet as assessed in our study.”
From Amino acids, lipid metabolites, and ferritin as potential mediators linking red meat consumption to type 2 diabetes (2015) · cites this paper as [48]
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Metadata
- Authors
- Krug, S., Kastenmüller, G., Stückler, F., Rist, M. J., Skurk, T., Sailer, M., Raffler, J., Römisch‐Margl, W., Adamski, J., Prehn, C., Frank, T., Engel, K., Hofmann, T., Luy, B., Zimmermann, R., Moritz, F., Schmitt‐Kopplin, P., Krumsiek, J., Kremer, W., Huber, F., Oeh, U., Theis, F. J., Szymczak, W., Hauner, H., Suhre, K., & Daniel, H.
- Affiliations
- Technical University of Munich (DE)
- Helmholtz Munich (DE)
- Department of General Food Technology Technische Universität München Freising‐Weihenstephan Germany
- Department of Food Chemistry and Molecular Sensory Science Technische Universität München Freising‐Weihenstephan Germany
- Karlsruhe Institute of Technology (DE)
- University of Regensburg (DE)
- LipoFIT Analytic GmbH Regensburg Germany
- TUM Klinikum (DE)
- Corresponding author
- Skurk, Thomas
- ORCID
- Kastenmüller, Gabi
- Rist, Manuela J.
- Skurk, Thomas
- Sailer, Manuela
- Raffler, Johannes
- Römisch‐Margl, Werner
- Adamski, Jerzy
- Prehn, Cornelia
- Engel, Karl‐Heinz
- Luy, Burkhard
- Zimmermann, Ralf
- Moritz, Franco
- Schmitt‐Kopplin, Philippe
- Krumsiek, Jan
- Kremer, Werner
- Theis, Fabian J.
- Hauner, Hans
- Suhre, Karsten
- Daniel, Hannelore
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2012-03-16
- Volume
- 26
- Issue
- 6
- Pages
- 2607-2619
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2096486669
- Cited by
- 327
- References
- 29
- Citations by year
- 2026: 8 · 2025: 10 · 2024: 19 · 2023: 11 · 2022: 22 · 2021: 21 · 2020: 36 · 2019: 13 · 2018: 25 · 2017: 29 · 2016: 27 · 2015: 30 · 2014: 34 · 2013: 35 · 2012: 7
- FWCI
- 13.62
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- University of Regensburg Publication Server (University of Regensburg) (submittedVersion)
- mediaTUM – the media and publications repository of the Technical University Munich (Technical University Munich) (submittedVersion)
- Site cant be reached (submittedVersion)
- Funders
- Studienstiftung des Deutschen Volkes
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolomics and Mass Spectrometry Studies
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Health, Environment, Cognitive Aging
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- fasting, oral glucose tolerance test, physical activity, cold stress, metabolic phenotypes, fatty acid beta-oxidation, fat mass, lipids, amino acids, exhaled breath condensate, urinary metabolites, blood metabolites, systems biology models
- MeSH terms
- Adult, Breath Tests, Carnitine, Cold Temperature, Fasting, Fatty Acids, Glucose Tolerance Test, Humans, Lipids, Male, Models, Biological, Magnetic Resonance Spectroscopy, Oxidation-Reduction, Stress, Physiological, Exercise, Lipid Metabolism, Metabolomics, Metabolome
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