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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. ; Grallert, H. ; Laumen, H. ; Seissler, J. ; Hauner, H.

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

Catal. Lett. 10, 386-401 (2014)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
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.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
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; Gene-environment Interactions; Glucagon-like Peptide-1; Glucose-tolerance Test; Insulin-resistance; Lipid-metabolism; Phosphatidylcholine Hydrolysis; Human Adipocytes; Rat Hepatocytes; Phospholipase-d; Acid Oxidation
ISSN (print) / ISBN 1011-372X
e-ISSN 1572-879X
Journal Catalysis Letters
Quellenangaben Volume: 10, Issue: 3, Pages: 386-401 Article Number: , Supplement: ,
Publisher Springer
Publishing Place New York, NY
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Epidemiology II (EPI2)
Institute of Experimental Genetics (IEG)
Institute of Bioinformatics and Systems Biology (IBIS)
Institute of Genetic Epidemiology (IGE)
Molekulare Endokrinologie und Metabolismus (MEM)
CCG Biomarker for the subclassification of T2DM (KKG-KDB)
German Center for Diabetes Reseach (DZD)