Diet-induced hypercholesterolemia alters liver glycosaminoglycans and associated-lipoprotein receptors in rats.

Glycosaminoglycans (GAGs) play an important
role in lipoprotein metabolism. In liver, it facilitates the
uptake of remnants through receptor-independent endocytosis.
However, changes in liver GAGs during diet-induced
hypercholesterolemia with normal levels of fat feeding are
unknown. Present paper highlights the effect of dietinduced
hypercholesterolemia with normal levels (5%) of
fat on liver GAGs and other associated lipoprotein receptors.
Hypercholesterolemia was induced in rats by feeding
diet supplemented with 0.5% cholesterol and 0.125% bile
salts. Hypercholesterolemia showed significantly decreased
GAGs of both heparan sulfate (HS) and chondroitin
sulfate/dermatan sulfate (CS/DS) classes of molecules.
Quantitative real-time polymerase chain reaction analysis
of GAG biosynthetic enzymes and other genes revealed
significant changes in expression profile. The decrease in
GAGs was prevented by simvastatin treatment; a drug that
inhibits endogenous cholesterol synthesis that was used as
a positive control in our study. Furthermore, there was a
comparatively decreased binding of GAGs from hypercholesterolemic
rats to lipoprotein lipase. LRP1 which plays a
major role in lipoprotein uptake was also significantly decreased,
and it was attenuated in simvastatin-treated hypercholesterolemic
rats. Furthermore, LDLR and ApoE were
also decreased significantly in liver of hypercholesterolemic
rats. Thus, diet-induced hypercholesterolemia results in dysregulation
of cholesterol homeostasis apparently through
changes in GAGs in conjunction with other associated
players.