title: Isotopomics: a top-down systems biology approach for understanding dynamic metabolism in rats using [1,2-(13)C(2)] acetate.
abstract: Isotope labeled tracers are commonly used to quantify the turnover rates of various metabolic intermediates and yield information regarding physiological regulation. Studies often only consider either one nutritional state (fasted or fed) and/or one question (e.g., measure of lipid or protein turnover). In this article, we consider a novel application combining the global approach of metabonomics with widespread stable isotope labeling as a way of being able to map metabolism in open mammalian systems, an approach we call "isotopomics". A total of 45 15-week-old male Zucker rats were administrated different amounts (from 0.5 to 8 mmol/kg) of sodium [1,2-(13)C(2)] acetate. Plasma samples taken at 1, 4, and 24 h were analyzed with (13)C nuclear magnetic resonance (NMR) and gas chromatography/mass spectrometry (GC/MS) to measure (13)C isotopic enrichment of 39 plasma metabolites across a wide range of compound classes (amino acids, short-chain fatty acids, lactate, glucose, and free fatty acids). Isotopic enrichment from 0.1-7.1 mole percent excess (MPE) for the highest dose could be reliably measured in 16 metabolites, and the kinetics of their (13)C isotopic enrichment are reported. Clustering metabolites based on (13)C kinetic curves enabled highlighting of time dependent patterns of (13)C distribution through the key metabolic pathways. These kinetic and quantitative data were reported into a biochemical map. This type of isotopomic approach for mapping dynamic metabolism in an open system has great potential for advancing our mechanistic knowledge of how different interventions and diseases can impact the metabolic response of animals and humans.
authors.affiliation: Nestlé Research Centre, Vers-Chez-les-Blanc, 1000 Lausanne 26, Switzerland. Jean-Philippe.Godin@rdls.nestle.com
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Godin
authors.forename: Alastair B
authors.initials: AB
authors.lastname: Ross
authors.forename: Serge
authors.initials: S
authors.lastname: Rezzi
authors.forename: Carine
authors.initials: C
authors.lastname: Poussin
authors.forename: Francois-Pierre
authors.initials: FP
authors.lastname: Martin
authors.forename: Andreas
authors.initials: A
authors.lastname: Fuerholz
authors.forename: Marilyn
authors.initials: M
authors.lastname: Cléroux
authors.forename: Anne-France
authors.initials: AF
authors.lastname: Mermoud
authors.forename: Lionel
authors.initials: L
authors.lastname: Tornier
authors.forename: Francia
authors.initials: F
authors.lastname: Arce Vera
authors.forename: Etienne
authors.initials: E
authors.lastname: Pouteau
authors.forename: Ziad
authors.initials: Z
authors.lastname: Ramadan
authors.forename: Sunil
authors.initials: S
authors.lastname: Kochhar
authors.forename: Laurent-Bernard
authors.initials: LB
authors.lastname: Fay
mesh_terms: D000818:Animals; D002247:Carbon Isotopes / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods*; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D008297:Male; D055432:Metabolomics; D015999:Multivariate Analysis; D051381:Rats; D019346:Sodium Acetate / Q000097:blood / Q000378:metabolism*; D013997:Time Factors
chemical_list: D002247:Carbon Isotopes; D019346:Sodium Acetate