Increasing evidence indicates that the intra-uterine environment has consequences for later life. However, the mechanisms of this fetal programming remain unclear. We aimed to investigate the impact of diet-induced maternal hypercholesterolemia on the predisposition of offspring to nonalcoholic fatty liver diseases (NAFLD) and metabolic diseases and its underlying mechanisms. Female apolipoprotein (Apo) E-deficient mice were fed a control diet (CD) or high fat/high cholesterol Western-type diet (WD) before and throughout pregnancy and lactation, and their offspring were weaned onto a CD postnatally. Strikingly, male offspring of WD-fed dams developed glucose intolerance and decreased peripheral insulin sensitivity and exhibited hepatic steatosis. Hepatic steatosis could be attributed, at least in part, to increased hepatic lipogenesis in E18.5 embryos and decreased serum VLDL levels in adulthood. In addition, males born to WD-fed dams had lower serum ApoB levels and hepatic ApoB gene expression compared with males born to CD-fed dams. DNA methylation analysis revealed increased methylation of CpG dinucleotides on the promoter region of the ApoB genes in the livers of male offspring of WD-fed dams. Our findings suggest that maternal WD intake can exacerbate the development of NAFLD in male offspring potentially by affecting ApoB gene expression through epigenetic alterations.
All Science Journal Classification (ASJC) codes
- Endocrinology, Diabetes and Metabolism
- Molecular Biology
- Nutrition and Dietetics
- Clinical Biochemistry