High cholesterol-supplemented diet during gestation and lactation alters liver glycosaminoglycans and associated lipoprotein receptors and results in fat accumulation in adulthood.

In utero insults to growing fetus impact its health in adulthood. Glycosaminoglycans (GAGs)
are involved in lipoprotein metabolism in the liver and vary both quantitively and qualitatively
on feeding adult rats a diet rich in cholesterol. However, no reports are available to
show the modulation of GAGs when the offspring are subjected to a high cholesterol diet in
gestation and lactation stages. Hypercholesterolemia in pregnant rats was induced by feeding
an AIN-93 diet supplemented with 0.5% cholesterol. The pups born to mothers fed with
high cholesterol diet showed a significant increase in cholesterol and triglycerides accumu-
lation in the liver. Quantitative changes in sulfated glycosaminoglycans (sGAGs), in particular
of heparan sulfate, were observed across the developmental stages. Other players involved
in lipoprotein metabolism, namely low-density lipoprotein receptor-related protein
1, apolipoprotein E, and low-density lipoprotein receptor expression levels, also showed differential
changes across developmental stages. Interestingly, when pups from hypercholes-
terolemic mothers were fed a normal diet after weaning until adulthood, a considerable
amount of fat accumulation in the liver was observed, implicating fetal exposure to early
high cholesterol exposure on long term health.