Maternal Diet‐Induced Hypercholesterolemia Programs Lipoprotein Metabolism by Increasing VLDL Particle Number and Size in C57BL6/J Mouse Progeny

Abstract

Early exposure to excessive cholesterol, in utero or in the early postnatal life, may program lipid metabolism in later life and predispose adult offspring to cardiovascular disease risk. However, little is known regarding the influence of maternal hypercholesterolemia on blood lipids and lipoprotein distribution throughout the life course. To better understand the influence of maternal hypercholesterolemia on blood lipids and lipoprotein distribution in offspring, blood lipid phenotyping was performed on newly‐weaned offspring (postnatal day 21) and chow‐fed adult offspring (postnatal day 84) born to mothers fed a chow diet or a chow diet supplemented with 0.15% cholesterol throughout gestation and lactation (n=6/group). Blood lipids including total‐C, HDL‐C, and LDL‐C were measured with enzymatic assay, and blood lipoprotein particle number and size were determined through nuclear magnetic resonance spectroscopy. Maternal serum total‐C during gestation (week 2) was higher (p≤0.05) in cholesterol‐supplemented dams compared with chow‐fed dams (87.5 ± 3.7 vs. 67.0 ± 3.5 mg/dL). Newly‐weaned and adult pups from chow or cholesterol‐supplemented mothers did not differ (p≥0.05) in serum lipid profile (total‐C, LDL‐C, or HDL‐C) or LDL and HDL particle number and size. However, both newly‐weaned pups and adult offspring born to cholesterol‐supplemented mothers demonstrated an increase (p≤0.05) in VLDL particle number and VLDL size compared with offspring from chow‐fed mothers. These results suggest that early exposure to cholesterol through maternal diet‐induced hypercholesterolemia influences VLDL distribution and size in newly‐weaned mouse offspring that persists into adulthood.Support or Funding InformationSupported by the National Institute for Complementary and Alternative Medicine.