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Lipid metabolism is associated with developmental epigenetic programming.

ABSTRACT: Maternal diet and metabolism impact fetal development. Epigenetic reprogramming facilitates fetal adaptation to these in utero cues. To determine if maternal metabolite levels impact infant DNA methylation globally and at growth and development genes, we followed a clinical birth cohort of 40 mother-infant dyads. Targeted metabolomics and quantitative DNA methylation were analyzed in 1st trimester maternal plasma (M1) and delivery maternal plasma (M2) as well as infant umbilical cord blood plasma (CB). We found very long chain fatty acids, medium chain acylcarnitines, and histidine were: (1) stable in maternal plasma from pregnancy to delivery, (2) significantly correlated between M1, M2, and CB, and (3) in the top 10% of maternal metabolites correlating with infant DNA methylation, suggesting maternal metabolites associated with infant DNA methylation are tightly controlled. Global DNA methylation was highly correlated across M1, M2, and CB. Thus, circulating maternal lipids are associated with developmental epigenetic programming, which in turn may impact lifelong health and disease risk. Further studies are required to determine the causal link between maternal plasma lipids and infant DNA methylation patterns.

SUBMITTER: Marchlewicz EH

PROVIDER: S-EPMC5054359 | biostudies-literature | 2016 Oct

REPOSITORIES: biostudies-literature

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Lipid metabolism is associated with developmental epigenetic programming.

Marchlewicz Elizabeth H EH Dolinoy Dana C DC Tang Lu L Milewski Samantha S Jones Tamara R TR Goodrich Jaclyn M JM Soni Tanu T Domino Steven E SE Song Peter X K PX F Burant Charles C Padmanabhan Vasantha V

Scientific reports 20161007

Maternal diet and metabolism impact fetal development. Epigenetic reprogramming facilitates fetal adaptation to these in utero cues. To determine if maternal metabolite levels impact infant DNA methylation globally and at growth and development genes, we followed a clinical birth cohort of 40 mother-infant dyads. Targeted metabolomics and quantitative DNA methylation were analyzed in 1st trimester maternal plasma (M1) and delivery maternal plasma (M2) as well as infant umbilical cord blood plasm ...[more]

PMID: 27713555

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Project description:BackgroundCell specific states of the chromatin are programmed during mammalian development. Dynamic DNA methylation across the developing embryo guides a program of repression, switching off genes in most cell types. Thus, the majority of the tissue specific differentially methylated sites (TS-DMS) must be un-methylated CpGs.Methodology and principal findingsComparison of expanded Methyl Sensitive Cut Counting data (eMSCC) among four tissues (liver, testes, brain and kidney) from three C57BL/6J mice, identified 138,052 differentially methylated sites of which 23,270 contain CpGs un-methylated in only one tissue (TS-DMS). Most of these CpGs were located in intergenic regions, outside of promoters, CpG islands or their shores, and up to 20% of them overlapped reported active enhancers. Indeed, tissue-specific enhancers were up to 30 fold enriched in TS-DMS. Testis showed the highest number of TS-DMS, but paradoxically their associated genes do not appear to be specific to the germ cell functions, but rather are involved in organism development. In the other tissues the differentially methylated genes are associated with tissue-specific physiological or anatomical functions. The identified sets of TS-DMS quantify epigenetic distances between tissues, generated during development. We applied this concept to measure the extent of reprogramming in the liver of mice exposed to in utero or early postnatal nutritional stress. Different protocols of food restriction reprogrammed the liver methylome in different but reproducible ways.Conclusion and significanceThus, each identified set of differentially methylated sites constituted an epigenetic signature that traced the developmental programing or the early nutritional reprogramming of each exposed mouse. We propose that our approach has the potential to outline a number of disease-associated epigenetic states. The composition of differentially methylated CpGs may vary with each situation, behaving as a composite variable, which can be used as a pre-symptomatic marker for disease.

Dataset Information

Lipid metabolism is associated with developmental epigenetic programming.

Publications

Lipid metabolism is associated with developmental epigenetic programming.

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