Hepatic uptake of beta-VLDL in cholesterol-fed rabbits.
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)
Department of Molecular Cell Biology, University of Oslo, Norway.
O
O
Gudmundsen
T
T
Berg
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N
Roos
M S
MS
Nenseter
D000818:Animals; D002791:Cholesterol, Dietary / Q000494:pharmacology; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D007728:Kupffer Cells / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism*; D008099:Liver / Q000166:cytology* / Q000378:metabolism*; D008297:Male; D008854:Microscopy, Electron; D011817:Rabbits; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein
D002791:Cholesterol, Dietary; D007457:Iodine Radioisotopes; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein