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

Saccenti E, van Duynhoven J, Jacobs DM, Smilde AK, Hoefsloot HC - PLoS ONE (2015)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Correlation among AA and LA parameters.Heat-map for the correlation matrix among the parameters describing AA and LA downstream metabolism, obtained using the estimated values obtained for the seven A parameters for the 12 subjects. There is no (or very weak) correlations between the AA and LA metabolites, suggesting that the formation of AA and LA metabolites is not related to each other.
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pone.0119856.g005: Correlation among AA and LA parameters.Heat-map for the correlation matrix among the parameters describing AA and LA downstream metabolism, obtained using the estimated values obtained for the seven A parameters for the 12 subjects. There is no (or very weak) correlations between the AA and LA metabolites, suggesting that the formation of AA and LA metabolites is not related to each other.

Mentions: To get an overview of the pathway-related and phenotypic differences in the AA and LA metabolism, principal component analysis (PCA) was performed on the phenotypic parameters A that were calculated for the AA (Table 4) and LA (Table 5) metabolites for each of the 12 subjects. From the biplot in Fig. 4 it becomes apparent that the first component is exclusively described by the LA metabolites, while the second component mostly explains the variation in AA metabolites. This indicates that the AA and LA pathways are independent. Also the correlation matrix (Fig. 5) calculated on the basis of the A parameters of the AA and LA metabolites across the subjects shows no strong correlations between the AA and LA metabolites, thus confirming that the formation of AA and LA metabolites is not related to each other. This is surprising considering that the same enzymes (LOX, CYP) are involved in the two pathways. For example, 15(S)-HETE and 13(S)-HODE are formed through the activity of the 15-LOX enzyme from AA and LA, respectively. Similarly, the CYP enzyme regulates the formation of 9,10-DiHOME from LA and 11,12-DiHETrE and 14,15-DiHETrE from AA.


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

Saccenti E, van Duynhoven J, Jacobs DM, Smilde AK, Hoefsloot HC - PLoS ONE (2015)

Correlation among AA and LA parameters.Heat-map for the correlation matrix among the parameters describing AA and LA downstream metabolism, obtained using the estimated values obtained for the seven A parameters for the 12 subjects. There is no (or very weak) correlations between the AA and LA metabolites, suggesting that the formation of AA and LA metabolites is not related to each other.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4364740&req=5

pone.0119856.g005: Correlation among AA and LA parameters.Heat-map for the correlation matrix among the parameters describing AA and LA downstream metabolism, obtained using the estimated values obtained for the seven A parameters for the 12 subjects. There is no (or very weak) correlations between the AA and LA metabolites, suggesting that the formation of AA and LA metabolites is not related to each other.
Mentions: To get an overview of the pathway-related and phenotypic differences in the AA and LA metabolism, principal component analysis (PCA) was performed on the phenotypic parameters A that were calculated for the AA (Table 4) and LA (Table 5) metabolites for each of the 12 subjects. From the biplot in Fig. 4 it becomes apparent that the first component is exclusively described by the LA metabolites, while the second component mostly explains the variation in AA metabolites. This indicates that the AA and LA pathways are independent. Also the correlation matrix (Fig. 5) calculated on the basis of the A parameters of the AA and LA metabolites across the subjects shows no strong correlations between the AA and LA metabolites, thus confirming that the formation of AA and LA metabolites is not related to each other. This is surprising considering that the same enzymes (LOX, CYP) are involved in the two pathways. For example, 15(S)-HETE and 13(S)-HODE are formed through the activity of the 15-LOX enzyme from AA and LA, respectively. Similarly, the CYP enzyme regulates the formation of 9,10-DiHOME from LA and 11,12-DiHETrE and 14,15-DiHETrE from AA.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus