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  • Review Article
  • Published:

Animal models of obesity and diabetes mellitus

Nature Reviews Endocrinology volume 14, pages 140–162 (2018)Cite this article

Subjects

Key Points

  • Development of safe and potent therapeutics is required to combat the obesity and diabetes mellitus pandemic

  • Animal models remain indispensable for discovering, validating and optimizing novel therapeutics for their safe use in humans

  • To improve the transition from bench to bedside, researchers must select the appropriate models, beware a myriad of confounding factors and draw appropriate conclusions

  • Experimental procedures and conditions should be accurately detailed to improve the reproducibility and translation of findings in preclinical animal models

  • Different animal models, ranging from non-mammalian models to non-human primates, each have distinct advantages and limitations

Abstract

More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models.

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Figure 1: Key advantages and disadvantages of different classes of animal models used in obesity and diabetes research.
Figure 2: Important experimental parameters and potential confounders of experimental outcomes in obesity and diabetes research and their interrelatedness.

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Authors and Affiliations

  1. Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, Neuherberg, D-85764, Germany

    Maximilian Kleinert, Christoffer Clemmensen, Timo D. Müller & Matthias H. Tschöp

  2. Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, D-80333, Germany

    Maximilian Kleinert, Christoffer Clemmensen, Timo D. Müller & Matthias H. Tschöp

  3. German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, Neuherberg, D-85764, Germany

    Maximilian Kleinert, Christoffer Clemmensen, Susanna M. Hofmann, Simone Renner, Peter Huypens, Johannes Beckers, Martin Hrabe de Angelis, Annette Schürmann, Mostafa Bakhti, Heiko Lickert, Eckhard Wolf, Timo D. Müller & Matthias H. Tschöp

  4. Department of Nutrition, Section of Molecular Physiology, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, DK-2200, Denmark

    Maximilian Kleinert

  5. Institute for Diabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, Neuherberg, D-85764, Germany

    Susanna M. Hofmann, Mostafa Bakhti & Heiko Lickert

  6. Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Ziemssenstr. 1, Munich, D-80336, Germany

    Susanna M. Hofmann

  7. Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, 37212, Tennessee, USA

    Mary C. Moore & Alan D. Cherrington

  8. Chair for Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilan University München, Feodor-Lynen-Str. 25, Munich, D-81377, Germany

    Simone Renner & Eckhard Wolf

  9. Department of Psychiatry and Behavioral Neuroscience, University of Cincinnati College of Medicine, Metabolic Diseases Institute, 2170 East Galbraith Road, Cincinnati, 45237, Ohio, USA

    Stephen C. Woods

  10. Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, Neuherberg, D-85764, Germany

    Peter Huypens, Johannes Beckers & Martin Hrabe de Angelis

  11. Technische Universität München, Chair of Experimental Genetics, Freising, D-85354, Germany

    Johannes Beckers & Martin Hrabe de Angelis

  12. Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114–116, Nuthetal, D-14558, Germany

    Annette Schürmann

  13. Institute of Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, Neuherberg, D-85764, Germany

    Mostafa Bakhti & Heiko Lickert

  14. Chair of Molecular Nutritional Medicine, Technische Universität München, TUM School of Life Sciences Weihenstephan, Gregor-Mendel-Str. 2, Freising, D-85354, Germany

    Martin Klingenspor

  15. Else Kröner-Fresenius Center for Nutritional Medicine, Technische Universität München, Freising, D-85354, Germany

    Martin Klingenspor

  16. Institute for Food & Health, Technische Universität München, Freising, D-85354, Germany

    Martin Klingenspor

  17. MicroBiome Therapeutics, 1316 Jefferson Ave, New Orleans, 70115, Louisiana, USA

    Mark Heiman

  18. Energy Metabolism Laboratory, Institute of Translational Medicine, Swiss Federal Institute of Technology (ETH) Zurich, Zurich-Schwerzenbach, CH-8603, Switzerland

    Michael Ristow

  19. Department of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition, 3135 Meyer Hall, University of California, Davis, 95616–5270, California, USA

    Peter J. Havel

Authors
  1. Maximilian Kleinert
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  2. Christoffer Clemmensen
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  3. Susanna M. Hofmann
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  4. Mary C. Moore
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  5. Simone Renner
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  6. Stephen C. Woods
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  7. Peter Huypens
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  11. Mostafa Bakhti
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  15. Michael Ristow
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  16. Heiko Lickert
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  17. Eckhard Wolf
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  18. Peter J. Havel
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  19. Timo D. Müller
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  20. Matthias H. Tschöp
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Contributions

M.Kle. and M.H.T conceptualized the review. All authors wrote parts of the review article, contributed to discussion of content and reviewed and/or edited the manuscript before submission.

Corresponding author

Correspondence to Matthias H. Tschöp.

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Competing interests

The authors declare no competing financial interests.

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Amphid neuron

Sensory neurons found in the anterior head region of the nematode Caenorhabditis elegans.

Four core genotypes

A mouse model system that dissociates the effects of the gonadal sex (testes or ovaries) from the effects of the sex chromosomes (XX or XY)121.

Envirotype

Factors that are exogenous to an organism.

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Kleinert, M., Clemmensen, C., Hofmann, S. et al. Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol 14, 140–162 (2018). https://doi.org/10.1038/nrendo.2017.161

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