Gene expression and DNA methylation as mechanisms of disturbed metabolism in offspring after exposure to a prenatal HF diet

J Lipid Res. 2019 Jul;60(7):1250-1259. doi: 10.1194/jlr.M092593. Epub 2019 May 7.


Exposure to a prenatal high-fat (HF) diet leads to an impaired metabolic phenotype in mouse offspring. The underlying mechanisms, however, are not yet fully understood. Therefore, this study investigated whether the impaired metabolic phenotype may be mediated through altered hepatic DNA methylation and gene expression. We showed that exposure to a prenatal HF diet altered the offspring's hepatic gene expression of pathways involved in lipid synthesis and uptake (SREBP), oxidative stress response [nuclear factor (erythroid-derived 2)-like 2 (Nrf2)], and cell proliferation. The downregulation of the SREBP pathway related to previously reported decreased hepatic lipid uptake and postprandial hypertriglyceridemia in the offspring exposed to the prenatal HF diet. The upregulation of the Nrf2 pathway was associated with increased oxidative stress levels in offspring livers. The prenatal HF diet also induced hypermethylation of transcription factor (TF) binding sites upstream of lipin 1 (Lpin1), a gene involved in lipid metabolism. Furthermore, DNA methylation of Lpin1 TF binding sites correlated with mRNA expression of Lpin1 These findings suggest that the effect of a prenatal HF diet on the adult offspring's metabolic phenotype are regulated by changes in hepatic gene expression and DNA methylation.

Keywords: deoxyribonucleic acid; development; diet and dietary lipids; epigenetics; high-fat diet; in utero; lipid metabolism; liver; microarrays; obesity; oxidative stress; pregnancy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Proliferation / drug effects
  • Cell Proliferation / genetics
  • DNA / metabolism
  • DNA Methylation / drug effects
  • DNA Methylation / genetics
  • Diet, High-Fat / adverse effects*
  • High-Throughput Nucleotide Sequencing
  • Lipid Metabolism / drug effects*
  • Lipid Metabolism / genetics*
  • Liver / drug effects
  • Liver / metabolism
  • Male
  • Mice, Inbred C57BL
  • Oxidation-Reduction / drug effects
  • Oxidative Stress / drug effects
  • Phosphatidate Phosphatase / genetics
  • Phosphatidate Phosphatase / metabolism
  • Real-Time Polymerase Chain Reaction


  • DNA
  • Lpin1 protein, mouse
  • Phosphatidate Phosphatase