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Metabolomics

, Volume 10, Issue 3, pp 386–401 | Cite as

Comparative analysis of plasma metabolomics response to metabolic challenge tests in healthy subjects and influence of the FTO obesity risk allele

  • Simone Wahl
  • Susanne Krug
  • Cornelia Then
  • Anna Kirchhofer
  • Gabi Kastenmüller
  • Tina Brand
  • Thomas Skurk
  • Melina Claussnitzer
  • Cornelia Huth
  • Margit Heier
  • Christa Meisinger
  • Annette Peters
  • Barbara Thorand
  • Christian Gieger
  • Cornelia Prehn
  • Werner Römisch-Margl
  • Jerzy Adamski
  • Karsten Suhre
  • Thomas Illig
  • Harald Grallert
  • Helmut LaumenEmail author
  • Jochen Seissler
  • Hans Hauner
Original Article

Abstract

The measurement of metabolites during intravenous or nutritional challenges may improve the identification of novel metabolic signatures which are not detectable in the fasting state. Here, we comprehensively characterized the plasma metabolomics response to five defined challenge tests and explored their use to identify interactions with the FTO rs9939609 obesity risk genotype. Fifty-six non-diabetic male participants of the KORA S4/F4 cohort, including 25 homozygous carriers of the FTO risk allele (AA genotype) and 31 carriers of the TT genotype were recruited. Challenges comprised an oral glucose tolerance test, a standardized high-fat high-carbohydrate meal and a lipid tolerance test, as well as an intravenous glucose tolerance test and a euglycemic hyperinsulinemic clamp. Blood was sampled for biochemical and metabolomics measurement before and during the challenges. Plasma samples were analyzed using a mass spectrometry-based metabolomics approach targeting 163 metabolites. Linear mixed-effects models and cluster analysis were performed. In both genotype groups, we observed significant challenge-induced changes for all major metabolite classes (amino acids, hexose, acylcarnitines, phosphatidylcholines, lysophosphatidylcholines and sphingomyelins, with corrected p-values ranging from 0.05 to 6.7E−37), which clustered in five distinct metabolic response profiles. Our data contribute to the understanding of plasma metabolomics response to diverse metabolic challenges, including previously unreported metabolite changes in response to intravenous challenges. The FTO genotype had only minor effects on the metabolite fluxes after standardized metabolic challenges.

Keywords

Metabolomics Metabolite profile Nutritional challenge Metabolic challenge Oral glucose tolerance test Oral lipid tolerance test Intravenous glucose tolerance test Clamp Obesity FTO Gene-environment interaction 

Notes

Acknowledgments

This work was funded by the Else Kroener-Fresenius Foundation, Bad Homburg v. d. H, Germany, the grant Virtual Institute ‘Molecular basis of glucose regulation and type 2 diabetes’ received from the Helmholtz Zentrum München, Neuherberg, Germany, the grant Clinical Cooperation Group ‘Nutrigenomics and type 2 diabetes’ received from the Helmholtz Zentrum München, Neuherberg, Germany, the Technische Universität München, Freising-Weihenstephan, and by funding from the German Federal Ministry for Education and Research (BMBF) to the German Center for Diabetes Research (DZD e. V.). WRM is funded by BMBF Grant no. 03IS2061B (project Gani_Med). KS is supported by ‘Biomedical Research Program’ funds at Weill Cornell Medical College in Qatar, a program funded by the Qatar Foundation. The KORA study group consists of A. Peters (speaker), R. Leidl, R. Holle, J. Heinrich, C. Meisinger, C. Strauch, and their coworkers, who are responsible for the design and conduct of the KORA studies. We gratefully acknowledge the contribution of all members of field staffs conducting the KORA study and thank all study probands participating in the study. The KORA research platform studies were initiated and financed by the Helmholtz Zentrum München – German Research Center for Environmental Health, which is funded by the German Federal Ministry of Education and Science, Research and Technology and by the State of Bavaria. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank Julia Scarpa, Katharina Sckell and Arsin Sabunchi for metabolomics measurement performed at the Helmholtz Zentrum München, Genome Analysis Center, Metabolomics Core Facility, Neuherberg, Germany, and Jan Krumsiek for advice concerning weighted enrichment analysis.

Conflict of interest

All authors declare that there is no conflict of interest.

Supplementary material

11306_2013_586_MOESM1_ESM.xlsx (68 kb)
Supplementary material 1 (XLSX 67 kb)
11306_2013_586_MOESM2_ESM.pdf (294 kb)
Supplementary material 2 (PDF 293 kb)

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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Simone Wahl
    • 1
    • 2
  • Susanne Krug
    • 3
    • 2
    • 4
    • 5
  • Cornelia Then
    • 6
    • 7
  • Anna Kirchhofer
    • 6
    • 7
  • Gabi Kastenmüller
    • 8
  • Tina Brand
    • 9
    • 4
    • 5
  • Thomas Skurk
    • 3
    • 4
    • 9
  • Melina Claussnitzer
    • 3
  • Cornelia Huth
    • 10
    • 2
  • Margit Heier
    • 10
  • Christa Meisinger
    • 10
    • 2
  • Annette Peters
    • 10
    • 2
  • Barbara Thorand
    • 10
    • 2
  • Christian Gieger
    • 11
  • Cornelia Prehn
    • 12
  • Werner Römisch-Margl
    • 8
  • Jerzy Adamski
    • 12
    • 13
    • 2
  • Karsten Suhre
    • 8
    • 14
  • Thomas Illig
    • 1
    • 15
  • Harald Grallert
    • 1
    • 2
    • 5
  • Helmut Laumen
    • 3
    • 2
    • 4
    • 5
    • 12
    Email author
  • Jochen Seissler
    • 6
    • 7
  • Hans Hauner
    • 3
    • 2
    • 4
    • 5
    • 9
  1. 1.Research Unit of Molecular EpidemiologyHelmholtz Zentrum München – German Research Center for Environmental HealthNeuherbergGermany
  2. 2.German Center for Diabetes Research (DZD)NeuherbergGermany
  3. 3.Else Kröner-Fresenius-Center for Nutritional Medicine, Chair of Nutritional MedicineTechnische Universität MünchenFreising-WeihenstephanGermany
  4. 4.ZIEL, Research Center for Nutrition and Food SciencesTechnische Universität MünchenFreising-WeihenstephanGermany
  5. 5.Clinical Cooperation Group Nutrigenomics and Type 2Technische Universität München and Helmholtz Zentrum MünchenMunichGermany
  6. 6.Medizinische Klinik and Poliklinik IV, Diabetes Zentrum – Campus InnenstadtKlinikum der Universität MünchenMunichGermany
  7. 7.Clinical Cooperation Group DiabetesLudwig-Maximilians-Universität München and Helmholtz Zentrum MünchenMunichGermany
  8. 8.Institute of Bioinformatics and Systems BiologyHelmholtz Zentrum München – German Research Center for Environmental HealthNeuherbergGermany
  9. 9.Else Kröner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der IsarTechnische Universität MünchenFreising-WeihenstephanGermany
  10. 10.Institute of Epidemiology IIHelmholtz Zentrum München – German Research Center for Environmental HealthNeuherbergGermany
  11. 11.Institute of Genetic EpidemiologyHelmholtz Zentrum München – German Research Center for Environmental HealthNeuherbergGermany
  12. 12.Institute of Experimental GeneticsHelmholtz Zentrum München – German Research Center for Environmental HealthNeuherbergGermany
  13. 13.Institute of Experimental Genetics, Life and Food Science Center WeihenstephanTechnische Universität MünchenFreising-WeihenstephanGermany
  14. 14.Department of Physiology and BiophysicsWeill Cornell Medical College in Qatar (WCMC-Q)DohaQatar
  15. 15.Medical School HannoverHannover Unified BiobankHanoverGermany

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