title: 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.
authors.affiliation: Department of Nutritional Medicine, Research Center for Nutrition and Food Sciences, Technische Universität München, Freising-Weihenstephan, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Krug
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Stückler
authors.forename: Manuela J
authors.initials: MJ
authors.lastname: Rist
authors.forename: Thomas
authors.initials: T
authors.lastname: Skurk
authors.forename: Manuela
authors.initials: M
authors.lastname: Sailer
authors.forename: Johannes
authors.initials: J
authors.lastname: Raffler
authors.forename: Werner
authors.initials: W
authors.lastname: Römisch-Margl
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.forename: Thomas
authors.initials: T
authors.lastname: Frank
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Engel
authors.forename: Thomas
authors.initials: T
authors.lastname: Hofmann
authors.forename: Burkhard
authors.initials: B
authors.lastname: Luy
authors.forename: Ralf
authors.initials: R
authors.lastname: Zimmermann
authors.forename: Franco
authors.initials: F
authors.lastname: Moritz
authors.forename: Philippe
authors.initials: P
authors.lastname: Schmitt-Kopplin
authors.forename: Jan
authors.initials: J
authors.lastname: Krumsiek
authors.forename: Werner
authors.initials: W
authors.lastname: Kremer
authors.forename: Fritz
authors.initials: F
authors.lastname: Huber
authors.forename: Uwe
authors.initials: U
authors.lastname: Oeh
authors.forename: Fabian J
authors.initials: FJ
authors.lastname: Theis
authors.forename: Wilfried
authors.initials: W
authors.lastname: Szymczak
authors.forename: Hans
authors.initials: H
authors.lastname: Hauner
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
authors.forename: Hannelore
authors.initials: H
authors.lastname: Daniel
mesh_terms: D000328:Adult; D001944:Breath Tests; D002331:Carnitine / Q000031:analogs & derivatives / Q000378:metabolism; D003080:Cold Temperature; D015444:Exercise; D005215:Fasting / Q000097:blood / Q000652:urine; D005227:Fatty Acids / Q000378:metabolism; D005951:Glucose Tolerance Test; D006801:Humans; D050356:Lipid Metabolism / Q000502:physiology; D008055:Lipids; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D055442:Metabolome / Q000502:physiology; D055432:Metabolomics; D008954:Models, Biological; D010084:Oxidation-Reduction; D013312:Stress, Physiological
chemical_list: D005227:Fatty Acids; D008055:Lipids; D002331:Carnitine