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Early life diet conditions the molecular response to post-weaning protein restriction in the mouse

Research output: Contribution to journalArticle

Amy F. Danson, Sarah J. Marzi, Robert Lowe, Michelle L. Holland, Vardhman K. Rakyan

Original languageEnglish
JournalBMC Biology
DOIs
Accepted/In press9 Apr 2018
Published2 May 2018

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Abstract

Background
Environmental influences fluctuate throughout the life course of an organism. It is therefore important to understand how the timing of exposure impacts molecular responses. Herein, we examine the responses of two key molecular markers of dietary stress, namely variant-specific methylation at ribosomal DNA (rDNA) and small RNA distribution, including tRNA fragments, in a mouse model of protein restriction (PR) with exposure at pre- and/or post-weaning.

Results
We first confirm that pre-weaning PR exposure modulates the methylation state of rDNA in a genotype-dependent manner, whereas post-weaning PR exposure has no such effect. Conversely, post-weaning PR induces a shift in small RNA distribution, but there is no effect in the pre-weaning PR model. Intriguingly, mice exposed to PR throughout their lives show neither of these two dietary stress markers, similar to controls.

Conclusions
The results show that the timing of the insult affects the nature of the molecular response but also, critically, that ‘matching’ diet exposure either side of weaning eliminates the stress response at the level of rDNA methylation and small RNA in sperm

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