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

Sven H. Rouschop, Tanja Karl, Angela Risch, Petronella A. van Ewijk, Vera B. Schrauwen-Hinderling, Antoon Opperhuizen, Frederik J. van Schooten, Roger W. Godschalk*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Web of Science)

Abstract

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.

Original languageEnglish
Pages (from-to)1250-1259
Number of pages10
JournalJournal of Lipid Research
Volume60
Issue number7
DOIs
Publication statusPublished - Jul 2019

Keywords

  • obesity
  • pregnancy
  • liver
  • microarrays
  • diet and dietary lipids
  • in utero
  • epigenetics
  • lipid metabolism
  • oxidative stress
  • development
  • deoxyribonucleic acid
  • high-fat diet
  • HIGH-FAT DIET
  • BODY-MASS INDEX
  • TRANSGENIC MICE
  • CHOLESTEROL-SYNTHESIS
  • LIVER-REGENERATION
  • ADAPTIVE RESPONSES
  • GLUCOSE-TOLERANCE
  • ACID SYNTHESIS
  • BINDING
  • PATHWAY

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