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

Journal of Lipid Research

Frederik J. van Schooten¹  Angela Risch²  Tanja Karl²  Antoon Opperhuizen³  Sven H. Rouschop³  Roger W. Godschalk³  Vera B. Schrauwen-Hinderling⁴  Petronella A. van Ewijk⁴ 

[1] Netherlands Food and Consumer Product Safety Authority (NVWA), Utrecht, The Netherlands;Department of BiosciencesUniversity of Salzburg, Salzburg, Austria;Department of Pharmacology and Toxicology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University, Maastricht, The Netherlands;Department of Radiology and Nuclear MedicineMaastricht University Medical Center, Maastricht, The Netherlands;

关键词: obesity;    pregnancy;    liver;    microarrays;    diet and dietary lipids;    in utero;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown