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Functional network analysis of obese and lean Göttingen minipigs elucidates changes in oxidative and inflammatory networks in obese pigs

Pflügers Archiv - European Journal of Physiology volume 466, pages 2167–2176 (2014)Cite this article

Abstract

The Göttingen minipig model of obesity is used in pre-clinical research to predict clinical outcome of new treatments for metabolic diseases. However, treatment effects often remain unnoticed when using single parameter statistical comparisons due to the small numbers of animals giving rise to large variation and insufficient statistical power. The purpose of this study was to perform a correlation matrix analysis of multiple multi-scale parameters describing co-segregation of traits in order to identify differences between lean and obese minipigs. More than 40 parameters, ranging from physical, cardiovascular, inflammatory and metabolic markers were measured in lean and obese animals. Correlation matrix analysis was performed using permutation test and bootstrapping at different levels of significance. Single parameter comparisons yielded significant differences between lean and obese animals mainly for known physical traits. On the other hand, functional network analysis revealed new co-segregations, particularly in the domain of inflammatory and oxidative stress markers in the obese animals that were not present in the lean. Functional networks of lean or obese minipigs could be utilised to assess drug effects and predict changes in parameters with a certain degree of precision, on the basis of the networks confidence intervals. Comparison of functional networks in minipigs with those of human clinical data may be used to identify common parameters or co-segregations related to obesity between animal models and man.

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Acknowledgments

The valuable technical assistance of Annie B. Kristensen, Joan Frandsen, Elisabeth Veyhe Andersen, Dennis Jensen, Christina Kjempf, Vibeke Christensen, Pia von Voss, Heidi Gertz Andersen and Charlott Kemp is gratefully acknowledged. The lean and obese Göttingen minipigs were funded by the SHARE Foundation and Danielsen’s Foundation and Novo Nordisk A/S, respectively. We acknowledge financial support by the Danish Heart Foundation (Project: R84-A3276-B1335).

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Authors and Affiliations

  1. Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark

    Harrie C. M. Boonen, Majid Sheykhzade & Jiaowei Tang

  2. Novo Nordisk A/S, Maaloev, Denmark

    Sophia G. Moesgaard & Berit Ø. Christoffersen

  3. Department of Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Malene M. Birck, Alan Mortensen, Lisbeth Høier Olsen & Jens Lykkesfeldt

  4. Department of Veterinary Clinical and Animal Sciences, Section of Animal Genetics, Breeding and Bioinformatics, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

    Susanna Cirera & Lars J. Jensen

  5. Innate Immunology Group, National Veterinary Institute, Technical University of Denmark, Copenhagen, Denmark

    Peter M. H. Heegaard & Tina Rødgaard Højbøge

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  1. Harrie C. M. Boonen
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  2. Sophia G. Moesgaard
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  3. Malene M. Birck
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  4. Berit Ø. Christoffersen
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  5. Susanna Cirera
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  6. Peter M. H. Heegaard
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  7. Tina Rødgaard Højbøge
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  8. Lars J. Jensen
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  9. Alan Mortensen
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  10. Lisbeth Høier Olsen
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  11. Majid Sheykhzade
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  12. Jiaowei Tang
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  13. Jens Lykkesfeldt
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Correspondence to Harrie C. M. Boonen.

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Boonen, H.C.M., Moesgaard, S.G., Birck, M.M. et al. Functional network analysis of obese and lean Göttingen minipigs elucidates changes in oxidative and inflammatory networks in obese pigs. Pflugers Arch - Eur J Physiol 466, 2167–2176 (2014). https://doi.org/10.1007/s00424-014-1486-2

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  • DOI: https://doi.org/10.1007/s00424-014-1486-2

Keywords

  • Functional network analysis
  • animal models
  • obesity
  • correlation matrix
  • Göttingen minipig