The dynamic range of the human metabolome revealed by challenges

Susanne Krug, Gabi Kastenmüller, Ferdinand Stückler, Manuela J. Rist, Thomas Skurk, Manuela Sailer, Johannes Raffler, Werner Römisch-Margl, Jerzy Adamski, Cornelia Prehn, Thomas Frank, Karl Heinz Engel, Thomas Hofmann, Burkhard Luy, Ralf Zimmermann, Franco Moritz, Philippe Schmitt-Kopplin, Jan Krumsiek, Werner Kremer, Fritz HuberUwe Oeh, Fabian J. Theis, Wilfried Szymczak, Hans Hauner, Karsten Suhre, Hannelore Daniel

Research output: Contribution to journalArticle

189 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)2607-2619
Number of pages13
JournalFASEB Journal
Issue number6
Publication statusPublished - 1 Jun 2012



  • Clinical study
  • Human physiology
  • Nutrition
  • Systems biology
  • Time-resolved fingerprinting

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

Cite this

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., ... Daniel, H. (2012). The dynamic range of the human metabolome revealed by challenges. FASEB Journal, 26(6), 2607-2619.