Early Exposure to Phytosterols Protects Offspring from Hypercholesterolemia Induced by Maternal Cholesterol Feeding in Syrian Golden Hamsters.

摘要

Pronounced maternal hyperlipidemia during pregnancy produces offspring who are predisposed to cardiovascular disease risk. As lipid-lowering drugs are contraindicated in pregnancy, we evaluated maternal phytosterol (PS) supplementation to protect against hyperlipidemia in offspring. Female Syrian golden hamsters were randomly assigned to three diets throughout pre-pregnancy (2 weeks), gestation, and lactation (n=6/group): (i) Chow only (Chow), (ii) chow with 0.5% cholesterol (CH), and (iii) chow with 0.5% cholesterol and 2% PS (CH/PS). Compared with 21 day-old pups from Chow dams, pups from dams fed the cholesterol-enriched diet displayed increases (p<0.05) in total-C (+68%), non-HDL-C (+123%), LDL-C (+154%), HDL-C (+30%), total LDL particle number (+216%), and VLDL particle number (+254%). CH-pups exhibited higher hepatic cholesterol deposition and differential mRNA expression pattern of cholesterol regulatory genes. Pups from PS-supplemented dams were protected against this dyslipidemic response with reductions (p<0.05) in total-C (-26%), non-HDL-C (-32%), and LDL-C (-29%) compared with the CH diet. However, serum triglycerides (TG) were increased (+62%) in pups from PS-fed mothers compared with pups from CH dams. Maternal PS supplementation reduced (p<0.05) hepatic cholesterol and increased the abundance of HMG-CoAr and LDLr protein in newly weaned offspring. Results suggest that maternal PS supplementation is effective in normalizing cholesterol in pups born to mothers with excessive hypercholesterolemia during pregnancy, however, the implications of increased blood TG concentrations is not known.