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Epigenetic germline inheritance of diet-induced obesity and insulin resistance

Nature Genetics volume 48, pages 497499 (2016) | Download Citation

Abstract

There is considerable controversy regarding epigenetic inheritance in mammalian gametes. Using in vitro fertilization to ensure exclusive inheritance via the gametes, we show that a parental high-fat diet renders offspring more susceptible to developing obesity and diabetes in a sex- and parent of origin–specific mode. The epigenetic inheritance of acquired metabolic disorders may contribute to the current obesity and diabetes pandemic.

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Acknowledgements

The authors are grateful for the expert technical assistance of M. Bamberger, A. Bettenbrock, S. Dunst, J. Wörner, M. Brückl, B. Rey and the animal caretakers of the German Mouse Clinic. This work was supported by grants from the Helmholtz Portfolio Theme 'Metabolic Dysfunction and Common Disease' (J.B.), the Helmholtz Alliance 'Imaging and Curing Environmental Metabolic Diseases' (ICEMED; J.B.) and the German Federal Ministry of Education and Research, INFRAFRONTIER grant 01KX1012 (M.H.d.A.).

Author information

Author notes

    • Martin Hrabě de Angelis
    •  & Johannes Beckers

    These authors contributed equally to this work.

Affiliations

  1. Institute of Experimental Genetics, Helmholtz Zentrum München, Neuherberg, Germany.

    • Peter Huypens
    • , Moya Wu
    • , Daniela Dyckhoff
    • , Susan Marschall
    • , Martin Hrabě de Angelis
    •  & Johannes Beckers
  2. German Mouse Clinic, Helmholtz Zentrum München, Neuherberg, Germany.

    • Peter Huypens
    • , Moya Wu
    • , Daniela Dyckhoff
    • , Susan Marschall
    • , Martin Hrabě de Angelis
    •  & Johannes Beckers
  3. German Center for Diabetes Research (DZD), Neuherberg, Germany.

    • Peter Huypens
    • , Daniela Dyckhoff
    • , Matthias Tschöp
    • , Martin Hrabě de Angelis
    •  & Johannes Beckers
  4. Institute of Computational Biology, Helmholtz Zentrum München, Neuherberg, Germany.

    • Steffen Sass
    •  & Fabian Theis
  5. Institute of Diabetes and Obesity, Helmholtz Zentrum München, Neuherberg, Germany.

    • Matthias Tschöp
  6. Division of Metabolic Diseases, Department of Medicine, Technische Universität München, Munich, Germany.

    • Matthias Tschöp
  7. Department of Mathematics, Technische Universität München, Garching, Germany.

    • Fabian Theis
  8. Chair of Experimental Genetics, Technische Universität München, Freising, Germany.

    • Martin Hrabě de Angelis
    •  & Johannes Beckers

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Contributions

P.H., M.T., M.H.d.A. and J.B. initiated the project and designed experiments. P.H., M.W., D.D. and S.M. performed the experiments. P.H., S.S., F.T. and J.B. analyzed data. P.H. and J.B. wrote the manuscript.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Peter Huypens or Johannes Beckers.

Integrated supplementary information

Supplementary information

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  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1–3.

Excel files

  1. 1.

    Supplementary Table 1

    Detailed diet composition.

  2. 2.

    Supplementary Table 2

    IVF details.

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DOI

https://doi.org/10.1038/ng.3527

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