Metabolism

Seeds of Metabolic Dysfunction Can Be Sewn in Early Life

Posted on 15 May 2020

Foetal under- or over-nutrition and early life exposure to certain chemicals can have a long-lasting impact on metabolic health, increasing the risk of developing obesity, diabetes and metabolic syndrome in adulthood.

Early exposure to certain chemicals (such as industrial chemicals and pesticides) can interfere with hormone function. It has recently emerged that these endocrine-disrupting chemicals can cause epigenetic alterations – long-lasting changes in gene expression that persist long after exposure, and make the development of metabolic diseases more likely. Consequently, researchers are interested in these chemicals as contributors to the metabolic disease epidemic.

Here, a study provides a proof-of-principle for this process in rats: they report that exposure to endocrine-disrupting chemicals during development caused epigenetic changes in the liver, most of which were equivalent to those observed during ageing. However, many reprogrammed genes remained silent until the rats were fed a western-style diet, whereupon they developed metabolic disruption relative to control rats that were fed the same diet.

Model of how developmental reprogramming can exaggerate response to a wester diet in adulthood.
Treviño, L., Dong, J., Kaushal, A., Katz, T., Jangid, R., & Robertson, M. et al. (2020). Epigenome environment interactions accelerate epigenomic aging and unlock metabolically restricted epigenetic reprogramming in adulthood. Nature Communications11(1). doi: 10.1038/s41467-020-15847-z

During early life, the epigenome is plastic, undergoing remodeling as part of normal development and aging processes. This plasticity creates a vulnerability to environmental exposures, which can disrupt the epigenome, and in the case of the EDC BPA, accelerate normal epigenomic aging to cause widespread epigenetic reprogramming. Later in life, epigenome:environment interactions can unmask the impact of this reprogramming, with the reprogrammed epigenome exhibiting aberrant responses to environmental challenges (ex. a Western-style diet).

Treviño, L., Dong, J., Kaushal, A., Katz, T., Jangid, R., & Robertson, M. et al. (2020). Epigenome environment interactions accelerate epigenomic aging and unlock metabolically restricted epigenetic reprogramming in adulthood. Nature Communications11(1). doi: 10.1038/s41467-020-15847-z

The fact that metabolic disruption due to chemical exposure seems to be dependant on environmental factors in later life suggests it may be possible to ameliorate, or even reverse these epigenetic changes before they can lead to disease.


References

Epigenome environment interactions accelerate epigenomic aging and unlock metabolically restricted epigenetic reprogramming in adulthood: https://doi.org/10.1038/s41467-020-15847-z

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