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Maternal Nutrition Induces Pervasive Gene Expression Changes but No Detectable DNA Methylation Differences in the Liver of Adult Offspring
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Details:
  • Pubmed ID:
    24594983
  • Pubmed Central ID:
    PMC3940881
  • Description:
    Aims

    Epidemiological and animal studies have shown that maternal diet can influence metabolism in adult offspring. However, the molecular mechanisms underlying these changes remain poorly understood. Here, we characterize the phenotypes induced by maternal obesity in a mouse model and examine gene expression and epigenetic changes induced by maternal diet in adult offspring.

    Methods

    We analyzed genetically identical male mice born from dams fed a high- or low-fat diet throughout pregnancy and until day 21 postpartum. After weaning, half of the males of each group were fed a high-fat diet, the other half a low-fat diet. We first characterized the genome-wide gene expression patterns of six tissues of adult offspring - liver, pancreas, white adipose, brain, muscle and heart. We then measured DNA methylation patterns in liver at selected loci and throughout the genome.

    Results

    Maternal diet had a significant effect on the body weight of the offspring when they were fed an obesogenic diet after weaning. Our analyses showed that maternal diet had a pervasive effect on gene expression, with a pronounced effect in liver where it affected many genes involved in inflammation, cholesterol synthesis and RXR activation. We did not detect any effect of the maternal diet on DNA methylation in the liver.

    Conclusions

    Overall, our findings highlighted the persistent influence of maternal diet on adult tissue regulation and suggested that the transcriptional changes were unlikely to be caused by DNA methylation differences in adult liver.

  • Document Type:
  • Collection(s):
  • Funding:
    DP1 HD075624/HD/NICHD NIH HHS/United States
    DP1 OD006911/OD/NIH HHS/United States
    DP1HD075624/DP/NCCDPHP CDC HHS/United States
    K01 DK084079/DK/NIDDK NIH HHS/United States
    K01 DK084079/DK/NIDDK NIH HHS/United States
    P40 RR012305/RR/NCRR NIH HHS/United States
    R01 DK08824/DK/NIDDK NIH HHS/United States
    R01 DK088824/DK/NIDDK NIH HHS/United States
    U24 DK76174/DK/NIDDK NIH HHS/United States
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