Global testing of shifts in metabolic phenotype

Parastoo Fazelzadeh, Huub C.J. Hoefsloot*, Thomas Hankemeier, Jasper Most, Sander Kersten, Ellen E. Blaak, Mark Boekschoten, John van Duynhoven

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Introduction: Current metabolomics approaches to unravel impact of diet- or lifestyle induced phenotype variation and shifts predominantly deploy univariate or multivariate approaches, with a posteriori interpretation at pathway level. This however often provides only a fragmented view on the involved metabolic pathways. Objectives: To demonstrate the feasibility of using Goeman’s global test (GGT) for assessment of variation and shifts in metabolic phenotype at the level of a priori defined pathways. Methods: Two intervention studies with identified phenotype variations and shifts were examined. In a weight loss (WL) intervention study obese subjects received a mixed meal challenge before and after WL. In a polyphenol (PP) intervention study obese subjects received a high fat mixed meal challenge (61E% fat) before and after a PP intervention. Plasma samples were obtained at fasting and during the postprandial response. Besides WL- and PP-induced phenotype shifts, also correlation of plasma metabolome with phenotype descriptors was assessed at pathway level. The plasma metabolome covered organic acids, amino acids, biogenic amines, acylcarnitines and oxylipins. Results: For the population of the WL study, GGT revealed that HOMA correlated with the fasting levels of the TCA cycle, BCAA catabolism, the lactate, arginine–proline and phenylalanine–tyrosine pathways. For the population of the PP study, HOMA correlated with fasting metabolite levels of TCA cycle, fatty acid oxidation and phenylalanine–tyrosine pathways. These correlations were more pronounced for metabolic pathways in the fasting state, than during the postprandial response. The effect of the WL and PP intervention on a priori defined metabolic pathways, and correlation of pathways with insulin sensitivity as described by HOMA was in line with previous studies. Conclusion: GGT confirmed earlier biological findings in a hypothesis led approach. A main advantage of GGT is that it provides a direct view on involvement of a priori defined pathways in phenotype shifts.

Original languageEnglish
Article number139
JournalMetabolomics
Volume14
Issue number10
DOIs
Publication statusPublished - 4 Oct 2018

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Polyphenols
Weight Loss
Phenotype
Fasting
Testing
Metabolic Networks and Pathways
Plasmas
Metabolome
Oxylipins
Fats
Meals
Biogenic Amines
Organic acids
Nutrition
Metabolites
Metabolomics
Lactic Acid
Fatty Acids
Population
Insulin Resistance

Keywords

  • Goeman’s global test
  • Metabolic pathways
  • Phenotype shifts

Cite this

Fazelzadeh, P., Hoefsloot, H. C. J., Hankemeier, T., Most, J., Kersten, S., Blaak, E. E., ... van Duynhoven, J. (2018). Global testing of shifts in metabolic phenotype. Metabolomics, 14(10), [139]. https://doi.org/10.1007/s11306-018-1435-8
Fazelzadeh, Parastoo ; Hoefsloot, Huub C.J. ; Hankemeier, Thomas ; Most, Jasper ; Kersten, Sander ; Blaak, Ellen E. ; Boekschoten, Mark ; van Duynhoven, John. / Global testing of shifts in metabolic phenotype. In: Metabolomics. 2018 ; Vol. 14, No. 10.
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abstract = "Introduction: Current metabolomics approaches to unravel impact of diet- or lifestyle induced phenotype variation and shifts predominantly deploy univariate or multivariate approaches, with a posteriori interpretation at pathway level. This however often provides only a fragmented view on the involved metabolic pathways. Objectives: To demonstrate the feasibility of using Goeman’s global test (GGT) for assessment of variation and shifts in metabolic phenotype at the level of a priori defined pathways. Methods: Two intervention studies with identified phenotype variations and shifts were examined. In a weight loss (WL) intervention study obese subjects received a mixed meal challenge before and after WL. In a polyphenol (PP) intervention study obese subjects received a high fat mixed meal challenge (61E{\%} fat) before and after a PP intervention. Plasma samples were obtained at fasting and during the postprandial response. Besides WL- and PP-induced phenotype shifts, also correlation of plasma metabolome with phenotype descriptors was assessed at pathway level. The plasma metabolome covered organic acids, amino acids, biogenic amines, acylcarnitines and oxylipins. Results: For the population of the WL study, GGT revealed that HOMA correlated with the fasting levels of the TCA cycle, BCAA catabolism, the lactate, arginine–proline and phenylalanine–tyrosine pathways. For the population of the PP study, HOMA correlated with fasting metabolite levels of TCA cycle, fatty acid oxidation and phenylalanine–tyrosine pathways. These correlations were more pronounced for metabolic pathways in the fasting state, than during the postprandial response. The effect of the WL and PP intervention on a priori defined metabolic pathways, and correlation of pathways with insulin sensitivity as described by HOMA was in line with previous studies. Conclusion: GGT confirmed earlier biological findings in a hypothesis led approach. A main advantage of GGT is that it provides a direct view on involvement of a priori defined pathways in phenotype shifts.",
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Fazelzadeh, P, Hoefsloot, HCJ, Hankemeier, T, Most, J, Kersten, S, Blaak, EE, Boekschoten, M & van Duynhoven, J 2018, 'Global testing of shifts in metabolic phenotype', Metabolomics, vol. 14, no. 10, 139. https://doi.org/10.1007/s11306-018-1435-8

Global testing of shifts in metabolic phenotype. / Fazelzadeh, Parastoo; Hoefsloot, Huub C.J.; Hankemeier, Thomas; Most, Jasper; Kersten, Sander; Blaak, Ellen E.; Boekschoten, Mark; van Duynhoven, John.

In: Metabolomics, Vol. 14, No. 10, 139, 04.10.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - Global testing of shifts in metabolic phenotype

AU - Fazelzadeh, Parastoo

AU - Hoefsloot, Huub C.J.

AU - Hankemeier, Thomas

AU - Most, Jasper

AU - Kersten, Sander

AU - Blaak, Ellen E.

AU - Boekschoten, Mark

AU - van Duynhoven, John

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N2 - Introduction: Current metabolomics approaches to unravel impact of diet- or lifestyle induced phenotype variation and shifts predominantly deploy univariate or multivariate approaches, with a posteriori interpretation at pathway level. This however often provides only a fragmented view on the involved metabolic pathways. Objectives: To demonstrate the feasibility of using Goeman’s global test (GGT) for assessment of variation and shifts in metabolic phenotype at the level of a priori defined pathways. Methods: Two intervention studies with identified phenotype variations and shifts were examined. In a weight loss (WL) intervention study obese subjects received a mixed meal challenge before and after WL. In a polyphenol (PP) intervention study obese subjects received a high fat mixed meal challenge (61E% fat) before and after a PP intervention. Plasma samples were obtained at fasting and during the postprandial response. Besides WL- and PP-induced phenotype shifts, also correlation of plasma metabolome with phenotype descriptors was assessed at pathway level. The plasma metabolome covered organic acids, amino acids, biogenic amines, acylcarnitines and oxylipins. Results: For the population of the WL study, GGT revealed that HOMA correlated with the fasting levels of the TCA cycle, BCAA catabolism, the lactate, arginine–proline and phenylalanine–tyrosine pathways. For the population of the PP study, HOMA correlated with fasting metabolite levels of TCA cycle, fatty acid oxidation and phenylalanine–tyrosine pathways. These correlations were more pronounced for metabolic pathways in the fasting state, than during the postprandial response. The effect of the WL and PP intervention on a priori defined metabolic pathways, and correlation of pathways with insulin sensitivity as described by HOMA was in line with previous studies. Conclusion: GGT confirmed earlier biological findings in a hypothesis led approach. A main advantage of GGT is that it provides a direct view on involvement of a priori defined pathways in phenotype shifts.

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KW - Goeman’s global test

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Fazelzadeh P, Hoefsloot HCJ, Hankemeier T, Most J, Kersten S, Blaak EE et al. Global testing of shifts in metabolic phenotype. Metabolomics. 2018 Oct 4;14(10). 139. https://doi.org/10.1007/s11306-018-1435-8