The role of diet and exercise in the transgenerational epigenetic landscape of T2DM

Key Points

  • Epigenetic processes have been implicated in the pathogenesis of type 2 diabetes mellitus

  • Diet and exercise might affect the epigenome over several generations

  • Epigenetic changes can be driven by DNA methylation and histone modification in response to environmental stressors

  • Regulation of gene expression by DNA methylation and histone modification occurs by a mechanism that impairs the access of transcriptional machinery to the promoters

  • Studying the epigenetic signatures of insulin resistance and the adaptive response to exercise might provide insight into gene–environment networks that control glucose and energy homeostasis.


Epigenetic changes are caused by biochemical regulators of gene expression that can be transferred across generations or through cell division. Epigenetic modifications can arise from a variety of environmental exposures including undernutrition, obesity, physical activity, stress and toxins. Transient epigenetic changes across the entire genome can influence metabolic outcomes and might or might not be heritable. These modifications direct and maintain the cell-type specific gene expression state. Transient epigenetic changes can be driven by DNA methylation and histone modification in response to environmental stressors. A detailed understanding of the epigenetic signatures of insulin resistance and the adaptive response to exercise might identify new therapeutic targets that can be further developed to improve insulin sensitivity and prevent obesity. This Review focuses on the current understanding of mechanisms by which lifestyle factors affect the epigenetic landscape in type 2 diabetes mellitus and obesity. Evidence from the past few years about the potential mechanisms by which diet and exercise affect the epigenome over several generations is discussed.

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Figure 1: The main forms of epigenetic modifications.
Figure 2: Putative effects of exercise and obesity on the predisposition to metabolic diseases.
Figure 3: Potential effect of environmentally induced epigenetic changes on gene expression.


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The authors are supported by grants to R.B. and J.R.Z. from the Novo Nordisk Foundation, and to J.R.Z. from the Swedish Research Council, The European Research Council and the Strategic Program in Diabetes Research at Karolinska Institutet.

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Both authors researched data for the article, contributed to discussion of the content, wrote the article and reviewed and/or edited the article before submission.

Correspondence to Juleen R. Zierath.

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Barrès, R., Zierath, J. The role of diet and exercise in the transgenerational epigenetic landscape of T2DM. Nat Rev Endocrinol 12, 441–451 (2016).

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