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Journal of Lipid Research, Vol 26, 465-472, Copyright © 1985 by Lipid Research, Inc.
DK Spady, SD Turley and JM Dietschy
The relationship between rates of hepatic sterol synthesis and rates of
hepatic low density lipoprotein (LDL) uptake (clearance) was studied in
animals with high (rats), low (female hamsters), and very low (male
hamsters) basal rates of hepatic sterol synthesis. In rats and female
hamsters, rates of hepatic sterol synthesis were varied over a 110-fold
range by feeding cholesterol or cholestyramine; nevertheless, rates of
hepatic LDL clearance remained essentially unchanged as did plasma LDL-
cholesterol concentrations. In contrast, in male hamsters, which have a
very limited capacity to synthesize cholesterol in the liver,
cholestyramine feeding increased rates of hepatic LDL uptake by 2.5- fold
and this was associated with a 50% reduction in plasma LDL- cholesterol
concentrations. The observed increase in LDL uptake was due to an increase
in receptor-dependent LDL transport while receptor- independent lipoprotein
uptake remained constant. These studies suggest that rates of hepatic
cholesterol synthesis and receptor-dependent LDL uptake are regulated
independently. Furthermore, the primary response of the liver to changes in
cholesterol availability is regulation of sterol synthesis and only when
the capacity of this compensatory mechanism is exceeded is the rate of LDL
transport altered.
ARTICLES
Rates of low density lipoprotein uptake and cholesterol synthesis are regulated independently in the liver
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