Influence of Maternal Hypercholesterolemia and Phytosterol Intervention During Gestation and Lactation on Dyslipidemia and Hepatic Lipid Metabolism in Offspring of Syrian Golden Hamsters

摘要

Although there is a normal physiological rise in maternal lipids during pregnancy, excessive maternal hyperlipidemia during pregnancy increases cardiovascular disease risk for both the mother and offspring. There are limited safe lipid-lowering treatment options for use during pregnancy, therefore, we evaluated the influence of maternal phytosterol (PS) supplementation on lipid and lipoprotein metabolism in mothers and progeny. Female Syrian golden hamsters were randomly assigned to three diets throughout pre-pregnancy, gestation, and lactation (n=6/group): (i) Chow (Chow), (ii) chow with 0.5% cholesterol (CH), and (iii) chow with 0.5% cholesterol and 2% PS (CH/PS). Compared with newly-weaned pups from Chow dams, pups from dams fed the cholesterol-enriched diet demonstrated increases (p<0.05) in total-C, LDL-C, HDL-C, and total LDL and VLDL particle number. Pups from cholesterol-fed mothers also exhibited higher hepatic cholesterol concentration and differential mRNA expression pattern of cholesterol regulatory genes. Pups from PS-supplemented dams demonstrated reductions (p<0.05) in serum total-C, non-HDL-C, and LDL-C but also increased triglycerides compared with pups from CH-fed dams. Maternal PS supplementation reduced (p<0.05) hepatic cholesterol and increased the abundance of HMG-CoAr and LDLr protein in newly-weaned pups compared with the CH group. Results suggest that maternal PS supplementation is largely effective in normalizing cholesterol in pups born to mothers with hypercholesterolemia, however, the cause and long-term influence of increased TG is not known.