Strategies for individual phenotyping of linoleic and arachidonic acid metabolism using an oral glucose tolerance test

PLoS One. 2015 Mar 18;10(3):e0119856. doi: 10.1371/journal.pone.0119856. eCollection 2015.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arachidonic Acid / blood*
  • Glucose Tolerance Test / methods*
  • Humans
  • Linoleic Acid / blood*
  • Metabolic Networks and Pathways / physiology*
  • Models, Biological*
  • Oxylipins / blood*
  • Phenotype*
  • Regression Analysis

Substances

  • Oxylipins
  • Arachidonic Acid
  • Linoleic Acid

Grants and funding

This project was financed by The Netherlands Metabolomics Centre (NMC), which is part of The Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research. DJ and JvD are employees of Unilever, a company that markets food products enriched with unsaturated fatty acids. Unilever provided support in the form of salaries for authors JvD and DJ, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.