Hypercholesterolemia protection by phytosterols in dyslipidemic mothers and their progeny

Background: In utero exposure to excessive cholesterol has been shown to increase fetal plasma cholesterol concentration and predispose adult offspring to cardiovascular disease (CVD) risk. As lipid-lowering drugs are contraindicated during pregnancy, natural cholesterol-lowering compounds may be a safe and effective alternative to reduce CVD risk in offspring born to hypercholesterolemic mothers.;Objective: This study utilized the hypercholesterolemic apolipoprotein E deficient (apoE-/-) mouse model to test the hypothesis that mothers supplemented with phytosterols (PS) during gestation and lactation would produce offspring with a more favorable cholesterol profile than offspring from unsupplemented mothers despite having a genetic predisposition toward hypercholesterolemia.;Methods: Sixteen female apoE-/- mice were randomly assigned to one of two diets fed throughout the gestation and lactation periods: a cholesterol enriched (0.15%) diet (CH) or the CH diet supplemented with PS (2%, CH/PS). Serum lipids and lipoproteins were measured by enzyme assay and nuclear magnetic resonance spectroscopy, respectively and liver cholesterol was analyzed by gas chromatography.;Results: Compared with the CH dams at the end of lactation, PS-supplemented dams displayed lower (p0.05) in HDL-C concentrations. Pups from PS-fed dams demonstrated lower ( p0.05) in HDL-C compared with pups from CH-fed dams. Furthermore, compared with pups from CH-fed dams, pups from PS-supplemented dams displayed a lower (p<0.05) number of total LDL particles (34%) and HDL particles (-30%).;Conclusions: Our results in apoE-/- mice suggest that even under strong genetic predisposition to hypercholesterolemia, pups born to mothers supplemented with PS during gestation and lactation exhibit favorable liver and serum cholesterol responses compared with pups from unsupplemented mothers.