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

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• 作者：Simone Wahl (1) (2)
  Susanne Krug (2) (3) (4) (5)
  Cornelia Then (6) (7)
  Anna Kirchhofer (6) (7)
  Gabi Kastenmüller (8)
  Tina Brand (4) (5) (9)
  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 R?misch-Margl (8)
  Jerzy Adamski (12) (13) (2)
  Karsten Suhre (14) (8)
  Thomas Illig (1) (15)
  Harald Grallert (1) (2) (5)
  Helmut Laumen (12) (2) (3) (4) (5)
  Jochen Seissler (6) (7)
  Hans Hauner (2) (3) (4) (5) (9)
  
• 关键词：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
• 刊名：Metabolomics
• 出版年：2014
• 出版时间：June 2014
• 年：2014
• 卷：10
• 期：3
• 页码：386-401
• 全文大小：1,037 KB
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• 作者单位：Simone Wahl (1) (2)
  Susanne Krug (2) (3) (4) (5)
  Cornelia Then (6) (7)
  Anna Kirchhofer (6) (7)
  Gabi Kastenmüller (8)
  Tina Brand (4) (5) (9)
  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 R?misch-Margl (8)
  Jerzy Adamski (12) (13) (2)
  Karsten Suhre (14) (8)
  Thomas Illig (1) (15)
  Harald Grallert (1) (2) (5)
  Helmut Laumen (12) (2) (3) (4) (5)
  Jochen Seissler (6) (7)
  Hans Hauner (2) (3) (4) (5) (9)
  
  1. Research Unit of Molecular Epidemiology, Helmholtz Zentrum München -German Research Center for Environmental Health, Neuherberg, Germany
  2. German Center for Diabetes Research (DZD), Neuherberg, Germany
  3. Else Kr?ner-Fresenius-Center for Nutritional Medicine, Chair of Nutritional Medicine, Technische Universit?t München, Gregor-Mendel-Str. 2, 85350, Freising-Weihenstephan, Germany
  4. ZIEL, Research Center for Nutrition and Food Sciences, Technische Universit?t München, Freising-Weihenstephan, Germany
  5. Clinical Cooperation Group Nutrigenomics and Type 2, Technische Universit?t München and Helmholtz Zentrum München, Munich, Germany
  6. Medizinische Klinik and Poliklinik IV, Diabetes Zentrum -Campus Innenstadt, Klinikum der Universit?t München, Munich, Germany
  7. Clinical Cooperation Group Diabetes, Ludwig-Maximilians-Universit?t München and Helmholtz Zentrum München, Munich, Germany
  8. Institute of Bioinformatics and Systems Biology, Helmholtz Zentrum München -German Research Center for Environmental Health, Neuherberg, Germany
  9. Else Kr?ner-Fresenius-Center for Nutritional Medicine, Klinikum rechts der Isar, Technische Universit?t München, Freising-Weihenstephan, Germany
  10. Institute of Epidemiology II, Helmholtz Zentrum München -German Research Center for Environmental Health, Neuherberg, Germany
  11. Institute of Genetic Epidemiology, Helmholtz Zentrum München -German Research Center for Environmental Health, Neuherberg, Germany
  12. Institute of Experimental Genetics, Helmholtz Zentrum München -German Research Center for Environmental Health, Neuherberg, Germany
  13. Institute of Experimental Genetics, Life and Food Science Center Weihenstephan, Technische Universit?t München, Freising-Weihenstephan, Germany
  14. Department of Physiology and Biophysics, Weill Cornell Medical College in Qatar (WCMC-Q), Doha, Qatar
  15. Medical School Hannover, Hannover Unified Biobank, Hanover, Germany
  
• ISSN：1573-3890

文摘

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?7), 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.