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 GrallertHelmut Laumen, Jochen Seissler, Hans Hauner

Research output: Contribution to journalArticle

7 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)386-401
Number of pages16
Issue number3
Publication statusPublished - 2014
Externally publishedYes



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

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry
  • Endocrinology, Diabetes and Metabolism

Cite this

Wahl, S., Krug, S., Then, C., Kirchhofer, A., Kastenmüller, G., Brand, T., Skurk, T., Claussnitzer, M., Huth, C., Heier, M., Meisinger, C., Peters, A., Thorand, B., Gieger, C., Prehn, C., Römisch-Margl, W., Adamski, J., Suhre, K., Illig, T., ... Hauner, H. (2014). Comparative analysis of plasma metabolomics response to metabolic challenge tests in healthy subjects and influence of the FTO obesity risk allele. Metabolomics, 10(3), 386-401.