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Epigenetic mechanisms that underpin metabolic and cardiovascular diseases

Nature Reviews Endocrinology volume 5, pages 401408 (2009) | Download Citation

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Abstract

Cellular commitment to a specific lineage is controlled by differential silencing of genes, which in turn depends on epigenetic processes such as DNA methylation and histone modification. During early embryogenesis, the mammalian genome is 'wiped clean' of most epigenetic modifications, which are progressively re-established during embryonic development. Thus, the epigenome of each mature cellular lineage carries the record of its developmental history. The subsequent trajectory and pattern of development are also responsive to environmental influences, and such plasticity is likely to have an epigenetic basis. Epigenetic marks may be transmitted across generations, either directly by persisting through meiosis or indirectly through replication in the next generation of the conditions in which the epigenetic change occurred. Developmental plasticity evolved to match an organism to its environment, and a mismatch between the phenotypic outcome of adaptive plasticity and the current environment increases the risk of metabolic and cardiovascular disease. These considerations point to epigenetic processes as a key mechanism that underpins the developmental origins of chronic noncommunicable disease. Here, we review the evidence that environmental influences during mammalian development lead to stable changes in the epigenome that alter the individual's susceptibility to chronic metabolic and cardiovascular disease, and discuss the clinical implications.

Key points

  • Developmental plasticity enables an organism to respond to environmental cues and adjust its phenotypic development to match its environment

  • Developmental plasticity is effected, at least in part, by epigenetic changes that are established in early life and modulate gene expression during development and maturity

  • In mammals, the window during which the epigenome is susceptible to nutritional cues extends from conception to at least weaning

  • Mismatch between the early and mature environments may result in inappropriate patterns of epigenetic changes and gene expression that increase subsequent susceptibility to metabolic and cardiovascular diseases

  • The available evidence suggests that interventions to prevent metabolic and cardiovascular diseases should focus on the prenatal and early postnatal periods

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Acknowledgements

P. D. Gluckman, T. Buklijas, F. M. Low and A. S. Beedle are funded by the National Research Centre for Growth and Development (New Zealand). M. A. Hanson is funded by the British Heart Foundation.

Désirée Lie, University of California, Irvine, CA, is the author of and is solely responsible for the content of the learning objectives, questions and answers of the Medscape-accredited continuing medical education activity associated with this article.

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Affiliations

  1. Centre for Human Evolution, Adaptation and Disease, Liggins Institute, The University of Auckland, Auckland, New Zealand.

    • Peter D. Gluckman
    • , Tatjana Buklijas
    • , Felicia M. Low
    •  & Alan S. Beedle
  2. Institute of Developmental Sciences, University of Southampton, Southampton, UK.

    • Mark A. Hanson

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The authors declare no competing financial interests.

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Correspondence to Peter D. Gluckman.

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https://doi.org/10.1038/nrendo.2009.102

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