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The Developmental Origins of Health and Disease hypothesis predicts that early-life environmental exposures can be detrimental to later-life health and that mismatch between the pre- and post-natal environment may contribute to the growing non-communicable disease epidemic. Within this is an increasingly recognized role for epigenetic mechanisms; for example, epigenetic modifications can be influenced by nutrition and can alter gene expression in mothers and offspring. Currently, there are few whole-genome transcriptional studies of response to nutritional alteration. Thus, we sought to explore how nutrition affects the expression of genes involved in epigenetic processes in  We manipulated  food macronutrient composition at the F0 generation, mismatched F1 offspring back to a standard diet and analysed the transcriptome of the F0-F3 generations by RNA sequencing. At F0, the altered (high-protein, low-carbohydrate) diet increased expression of genes classified as having roles in epigenetic processes, with co-ordinated down-regulation of genes involved in immunity, neurotransmission and neurodevelopment, oxidative stress and metabolism. Upon reversion to standard nutrition, mismatched F1 and F2 generations displayed multigenerational inheritance of altered gene expression. By the F3 generation, gene expression had reverted to F0 (matched) levels. These nutritionally induced gene expression changes demonstrate that dietary alterations can up-regulate epigenetic genes, which may influence the expression of genes with broad biological functions. Furthermore, the multigenerational inheritance of the gene expression changes in F1 and F2 mismatched generations suggests a predictive adaptive response to maternal nutrition, aiding the understanding of the interaction between maternal diet and offspring health, with direct implications for the current non-communicable disease epidemic.

current zoology/environmental epigenetics/current zoology

A ‘phenotypic hangover’: the predictive adaptive response and multigenerational effects of altered nutrition on the transcriptome of Drosophila melanogaster