Krug, Susanne and Kastenmueller, Gabi and Stueckler, Ferdinand and Rist, Manuela J. and Skurk, Thomas and Sailer, Manuela and Raffler, Johannes and Roemisch-Margl, Werner and Adamski, Jerzy and Prehn, Cornelia and Frank, Thomas and Engel, Karl-Heinz and Hofmann, Thomas and Luy, Burkhard and Zimmermann, Ralf and Moritz, Franco and Schmitt-Kopplin, Philippe and Krumsiek, Jan and Kremer, Werner and Huber, Fritz and Oeh, Uwe and Theis, Fabian J. and Szymczak, Wilfried and Hauner, Hans and Suhre, Karsten and Daniel, Hannelore (2012) The dynamic range of the human metabolome revealed by challenges. FASEB JOURNAL, 26 (6). pp. 2607-2619. ISSN 0892-6638,
Full text not available from this repository. (Request a copy)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 beta-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., Kastenmuller, G., Stuckler, F., Rist, M. J., Skurk, T., Sailer, M., Raffler, J., Romisch-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
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MITOCHONDRIAL BETA-OXIDATION; MASS-SPECTROMETRY; DISEASE; BIOMARKERS; URINE; clinical study; human physiology; nutrition; systems biology; time-resolved fingerprinting |
| Subjects: | 500 Science > 570 Life sciences |
| Divisions: | Biology, Preclinical Medicine > Institut für Biophysik und physikalische Biochemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 13 May 2020 05:21 |
| Last Modified: | 13 May 2020 05:21 |
| URI: | https://pred.uni-regensburg.de/id/eprint/18654 |
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