Hepatic uptake of beta-VLDL in cholesterol-fed rabbits
| Autor: | Trond Berg, Norbert Roos, Ola Gudmundsen, Marit S. Nenseter |
|---|---|
| Rok vydání: | 1993 |
| Předmět: |
Male
Very low-density lipoprotein medicine.medical_specialty Apolipoprotein B Kupffer Cells Receptors Cell Surface QD415-436 In Vitro Techniques Lipoproteins VLDL Biology Biochemistry Cholesterol Dietary Iodine Radioisotopes chemistry.chemical_compound Endocrinology In vivo Internal medicine medicine Animals Receptor Receptors Lipoprotein Cholesterol Liver cell Cell Biology Lipoproteins LDL Microscopy Electron Liver chemistry Low-density lipoprotein biology.protein lipids (amino acids peptides and proteins) Rabbits Lipoprotein |
| Zdroj: | Journal of Lipid Research, Vol 34, Iss 4, Pp 589-600 (1993) |
| ISSN: | 0022-2275 |
| DOI: | 10.1016/s0022-2275(20)39982-x |
| Popis: | The hepatic uptake of intravenously injected P-very low density lipoprotein (8-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 P-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 con- trol rabbits (P < 0.05). Although this is a fractional reduction, it represents a more than 10-fold increase in absolute hepatic up- take 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 in- jected 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 8- VLDL in the parenchymal cells, and this, together with an in- creased competition for binding sites in the hypercholestero- lemic rabbits, probably explains the reduced uptake of 0-VLDL in terms of % of injected dose observed in vivo. In vitro data suggested that the receptor involved in both hypercholestero- lemic 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 109 cells; this uptake was reduced to 1.1 f 0.5% in hyper- cholesterolemic animals. No differences in uptake of P-VLDL in nonparenchymal liver cells were observed on a per cell basis be- tween the two feeding groups, indicating that binding sites in- volved in this uptake are not down-regulated by cholesterol feed- ing. On the contrary, the absolute uptake in the nonparenchymal liver cells is greatly increased in hyper- cholesterolemic rabbits as compared to controls. In cholesterol- fed rabbits the three different liver cell types took up approxi- mately the same amount of P-VLDL per cell. The liver non- parenchymal cells, therefore, assume a prominent role in uptake of 0-VLDL in hypercholesterolemic rabbits, accounting for more than 30% of the total hepatic uptake as compared to 16% in control animals. Electron microscopic studies showed a significant accumulation of lipids in all cell types investigated from cholesterol-fed rabbits, while no such lipid accretion could be observed in control rabbits. The in vivo data show that the nonparenchymal cells, notably the Kupffer cells, play an impor- tant role in catabolizing P-VLDL in hypercholesterolemic rab- bits.-Gudmundsen, O., T. Berg, N. Roos, and M. S. Nen- seter. Hepatic uptake of P-VLDL in cholesterol-fed rabbits. J. Lipid Res. 1993. 34: 589-600. |
| Databáze: | OpenAIRE |
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