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Metabolomics of prolonged fasting in humans reveals new catabolic markers

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Abstract

Fasting is one of the simplest metabolic challenges that can be performed in humans. We here report for the first time a comprehensive analysis of the human “fasting metabolome” obtained from analysis of plasma and urine samples in a small cohort of healthy volunteers, using nuclear magnetic resonance (NMR), gas chromatography- and liquid chromatography-mass spectrometry (GC-MS and LC-MS). Intra- and inter-individual variation of metabolites was on measurement of four overnight fasting samples collected from each volunteer over a four week period. One additional sample per volunteer was collected following a prolonged fasting period of 36 h. Amongst a total of 377 quantified entities in plasma around 44% were shown to change significantly in concentration when volunteers extended fasting from 12 to 36 h. In addition to known markers (plasma free fatty acids, glycerol, ketone bodies) that reflect changes in the body’s fuel management under fasting conditions a wide range of “new” entities such as α-aminobutyrate as well as other amino and keto acids were identified as fasting markers. Based on multiple correlations amongst the metabolites and selected hormones in plasma such as leptin or insulin-like-growth-factor-1 (IGF-1), a robust metabolic network with coherent regulation of a wide range of metabolites could be identified. The metabolomics approach described here demonstrates the plasticity of human metabolism and identifies new and robust markers of the fasting state.

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Acknowledgments

This study was funded by the European Nutrigenomics Organisation, an EC funded Network of Excellence, grant No: FOOD-2004-506360. We kindly thank all members of the NuGO PPS Study for excellent cooperation and productive scientific discussions. We specifically would like to thank Karen Ross and Lynn Pirie for their help with the sample preparation work, Barbara Gelhaus, Mark Philo, Ronny Scheundel, Hermine Kienberger and Johanna Welzhofer for excellent technical assistance.

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Authors and Affiliations

  1. Molecular Nutrition Unit, ZIEL—Research Center for Nutrition and Food Sciences, Technische Universität München, Gregor-Mendel-Str. 2, 85350, Freising-Weihenstephan, Germany

    Isabel Rubio-Aliaga, Gabriele Schmidt, Carolin Heim & Hannelore Daniel

  2. Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, UK

    Baukje de Roos, Susan J. Duthie & L. Katie Crosley

  3. Biomathematics and Statistics Scotland, Aberdeen, Scotland, UK

    Claus Mayer & Graham Horgan

  4. Institute of Food Research, Norwich Research Park, Norwich, UK

    Ian J. Colquhoun, Gwénaëlle Le Gall, Francis Mulholland, Ian T. Johnson, Abigael C. Polley & Ruan M. Elliott

  5. LIPOFIT Analytics GmbH, Regensburg, Germany

    Fritz Huber & Werner Kremer

  6. Bioanalytik Weihenstephan, ZIEL—Research Center for Nutrition and Food Sciences, Technische Universität München, Freising-Weihenstephan, Germany

    Michael Rychlik

  7. Physiological Genomics, TNO-Quality of Life, Zeist, The Netherlands

    Suzan Wopereis & Ben van Ommen

  8. Functional Genetics, Maastricht University, Maastricht, The Netherlands

    Freek G. Bouwman & Edwin C. Mariman

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  1. Isabel Rubio-Aliaga
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  2. Baukje de Roos
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  3. Susan J. Duthie
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  4. L. Katie Crosley
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  5. Claus Mayer
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  6. Graham Horgan
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  7. Ian J. Colquhoun
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  8. Gwénaëlle Le Gall
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  9. Fritz Huber
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  10. Werner Kremer
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  14. Gabriele Schmidt
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  15. Carolin Heim
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  16. Freek G. Bouwman
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  17. Edwin C. Mariman
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  18. Francis Mulholland
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  19. Ian T. Johnson
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  20. Abigael C. Polley
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  21. Ruan M. Elliott
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  22. Hannelore Daniel
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Correspondence to Hannelore Daniel.

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Rubio-Aliaga, I., de Roos, B., Duthie, S.J. et al. Metabolomics of prolonged fasting in humans reveals new catabolic markers. Metabolomics 7, 375–387 (2011). https://doi.org/10.1007/s11306-010-0255-2

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  • DOI: https://doi.org/10.1007/s11306-010-0255-2

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