Format

Send to

Choose Destination
J Lipid Res. 2019 May 7. pii: jlr.M092593. doi: 10.1194/jlr.M092593. [Epub ahead of print]

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

Author information

1
Maastricht University, Netherlands.
2
Salzburg University, Austria.
3
Maastricht University, Netherlands; r.godschalk@maastrichtuniversity.nl.

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 (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 binding sites upstream of Lpin1, a gene involved in lipid metabolism. Furthermore, DNA methylation of Lpin1 transcription factor 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:

Development; Diet and dietary lipids; Epigenetics; In utero; Lipid metabolism; Liver; Microarrays; Obesity; Oxidative stress; Pregnancy

PMID:
31064776
DOI:
10.1194/jlr.M092593
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center