Alterations in hepatic gene expression and DNA methylation as underlying mechanisms of disturbed metabolism in adult mouse offspring after exposure to a prenatal high fat diet
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 could have been mediated through altered hepatic DNA methylation and gene expression. In this study, both parent mice received a HF or low fat (LF) diet before and during pregnancy, and throughout lactation, after which offspring was weaned onto a HF diet. Previous work showed that at 12 weeks of age, the offspring displayed postprandial hypertriglyceridemia, which related to an impaired clearance of lipids from the blood into the liver after a HF meal. To study the mechanisms underlying the impaired metabolic phenotype after prenatal exposure to a HF diet, hepatic genome-wide gene expression was studied using whole transcript microarrays. In addition, hepatic DNA methylation of selected genes was assessed by bisulphite pyrosequencing.
Overall design
Male offspring mice were sacrificed at 12 and 28 weeks of age. Livers were obtained and total RNA was isolated for microarray hybridization. In total, 32 samples were included: for week 12, n=7 per group (prenatal HF or LF) and for week 28, n=9 per group.
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