Abstract
BackgroundConsumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated. Selenium and folate are two compounds which influence epigenetic mechanisms. We investigated the hypothesis that post-weaning supplementation with adequate levels of selenium and folate in offspring of female mice fed a high-fat, low selenium and folate diet during gestation and lactation will lead to epigenetic changes of potential importance for long-term health.MethodsFemale offspring of mothers fed the experimental diet were either maintained on this diet (HF-low-low), or weaned onto a high-fat diet with sufficient levels of selenium and folate (HF-low-suf), for 8 weeks. Gene and protein expression, DNA methylation, and histone modifications were measured in colon and liver of female offspring.ResultsAdequate levels of selenium and folate post-weaning affected gene expression in colon and liver of offspring, including decreasing Slc2a4 gene expression. Protein expression was only altered in the liver. There was no effect of adequate levels of selenium and folate on global histone modifications in the liver. Global liver DNA methylation was decreased in mice switched to adequate levels of selenium and folate, but there was no effect on methylation of specific CpG sites within the Slc2a4 gene in liver.ConclusionsPost-weaning supplementation with adequate levels of selenium and folate in female offspring of mice fed high-fat diets inadequate in selenium and folate during gestation and lactation can alter global DNA methylation in liver. This may be one factor through which the negative effects of a poor diet during early life can be ameliorated. Further research is required to establish what role epigenetic changes play in mediating observed changes in gene and protein expression, and the relevance of these changes to health.
Highlights
Consumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated
Food intake and body weight There was no effect of adequate levels of selenium and folate post-weaning on food intake (c. 2.7 g diet/day; P = 0.91) or bodyweight (c. 18.5 g; P = 0.66) of offspring
The data described here show that in addition to changes in gene and protein expression in metabolic and oxidative pathways, altering dietary levels of selenium and folate post-weaning can alter global DNA methylation. Because epigenetic mechanisms such as DNA methylation may have a role in disease processes, modulation of these by micronutrient supplementation may play a role in preventing or ameliorating negative health outcomes from inadequate nutrition
Summary
Consumption of high-fat diets has negative impacts on health and well-being, some of which may be epigenetically regulated. We investigated the hypothesis that post-weaning supplementation with adequate levels of selenium and folate in offspring of female mice fed a high-fat, low selenium and folate diet during gestation and lactation will lead to epigenetic changes of potential importance for long-term health. The epigenome comprises interconnected, interdependent heritable processes (including DNA methylation, histone modifications, and non-coding RNAs) that regulate gene expression in response to environmental influences. There is mounting evidence that epigenetics has a major role in multiple physiological processes including development, imprinting, and regulation of gene transcription [2]. It is important to investigate the potential of food components to induce phenotypic changes via epigenetic modulation of gene expression [9]
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