Journal of Lipid Research, Vol 34, 589-600, Copyright © 1993 by Lipid Research, Inc.
Hepatic uptake of beta-VLDL in cholesterol-fed rabbits
O Gudmundsen, T Berg, N Roos and MS Nenseter
Department of Molecular Cell Biology, University of Oslo, Norway.
The hepatic uptake of intravenously injected beta-very low density
lipoprotein (beta-VLDL) in rabbits fed 2% (w/w) cholesterol for 3 weeks was
investigated. In vitro studies were also conducted to examine the
specificity and the capacity of the uptake in isolated liver parenchymal
cells. The hepatic uptake of beta-VLDL was 15.8 +/- 6.7% (n = 6) in the
cholesterol-fed rabbits as compared to 26.6 +/- 7.5% (n = 6) of the
injected dose in control rabbits (P < 0.05). Although this is a
fractional reduction, it represents a more than 10-fold increase in
absolute hepatic uptake of lipoproteins in the cholesterol-fed rabbits. In
these animals the liver parenchymal, endothelial, and Kupffer cells took up
10.2 +/- 2.7%, 3.0 +/- 0.9%, and 1.8 +/- 0.4% of the injected dose,
respectively, compared to 25.9 +/- 6.1%, 3.6 +/- 1.6%, and 1.5 +/- 0.8% of
the injected dose in chow-fed controls. However, taking into account the
high plasma lipoprotein levels in the cholesterol-fed rabbits, the absolute
cellular uptake was 10-fold increased in the parenchymal liver cells and
more than 20-fold increased in the nonparenchymal cells. In vitro results
indicated a 40% down-regulation of the specific receptor for beta-VLDL in
the parenchymal cells, and this, together with an increased competition for
binding sites in the hypercholesterolemic rabbits, probably explains the
reduced uptake of beta-VLDL in terms of % of injected dose observed in
vivo. In vitro data suggested that the receptor involved in both
hypercholesterolemic and normolipemic rabbits was the apolipoprotein (apo)
B,E receptor. On a per cell basis, parenchymal cells from chow-fed control
animals took up 2.4 +/- 0.8% of the injected dose per 10(9) cells; this
uptake was reduced to 1.1 +/- 0.5% in hypercholesterolemic animals. No
differences in uptake of beta-VLDL in nonparenchymal liver cells were
observed on a per cell basis between the two feeding groups, indicating
that binding sites involved in this uptake are not down-regulated by
cholesterol feeding. On the contrary, the absolute uptake in the
nonparenchymal liver cells is greatly increased in hypercholesterolemic
rabbits as compared to controls. In cholesterol-fed rabbits the three
different liver cell types took up approximately the same amount of
beta-VLDL per cell. The liver nonparenchymal cells, therefore, assume a
prominent role in uptake of beta-VLDL in hypercholesterolemic rabbits,
accounting for more than 30% of the total hepatic uptake as compared to 16%
in control animals.(ABSTRACT TRUNCATED AT 400 WORDS)
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