title: Strategies for individual phenotyping of linoleic and arachidonic acid metabolism using an oral glucose tolerance test.
abstract: The ability to restore homeostasis upon environmental challenges has been proposed as a measure for health. Metabolic profiling of plasma samples during the challenge response phase should offer a profound view on the flexibility of a phenotype to cope with daily stressors. Current data modeling approaches, however, struggle to extract biological descriptors from time-resolved metabolite profiles that are able to discriminate between different phenotypes. Thus, for the case of oxylipin responses in plasma upon an oral glucose tolerance test we developed a modeling approach that incorporates a priori biological pathway knowledge. The degradation pathways of arachidonic and linoleic acids were modeled using a regression model based on a pseudo-steady-state approximated model, resulting in a parameter A that summarizes the relative enzymatic activity in these pathways. Analysis of the phenotypic parameters As suggests that different phenotypes can be discriminated according to preferred relative activity of the arachidonic and linoleic pathway. Correlation analysis shows that there is little or no competition between the arachidonic and linoleic acid pathways, although they share the same enzymes.
authors.affiliation: Laboratory of Systems and Synthetic Biology, University of Wageningen and Research Center, Wageningen, The Netherlands; Biosystem Data Analysis Group, University of Amsterdam, Amsterdam, The Netherlands; Netherlands Metabolomics Centre, Leiden, The Netherlands.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Saccenti
authors.affiliation: Unilever Research & Development, Vlaardingen, The Netherlands; Laboratory of Biophysics, University of Wageningen and Research Center, Wageningen, The Netherlands; Netherlands Metabolomics Centre, Leiden, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: van Duynhoven
authors.affiliation: Unilever Research & Development, Vlaardingen, The Netherlands; Netherlands Metabolomics Centre, Leiden, The Netherlands.
authors.forename: Doris M
authors.initials: DM
authors.lastname: Jacobs
authors.affiliation: Biosystem Data Analysis Group, University of Amsterdam, Amsterdam, The Netherlands; Netherlands Metabolomics Centre, Leiden, The Netherlands.
authors.forename: Age K
authors.initials: AK
authors.lastname: Smilde
authors.affiliation: Biosystem Data Analysis Group, University of Amsterdam, Amsterdam, The Netherlands; Netherlands Metabolomics Centre, Leiden, The Netherlands.
authors.forename: Huub C J
authors.initials: HC
authors.lastname: Hoefsloot
mesh_terms: D016718:Arachidonic Acid / Q000097:blood*; D005951:Glucose Tolerance Test / Q000379:methods*; D006801:Humans; D019787:Linoleic Acid / Q000097:blood*; D053858:Metabolic Networks and Pathways / Q000502:physiology*; D008954:Models, Biological; D054883:Oxylipins / Q000097:blood*; D010641:Phenotype; D012044:Regression Analysis
chemical_list: D054883:Oxylipins; D016718:Arachidonic Acid; D019787:Linoleic Acid