Metabolism of canine beta-very low density lipoproteins in normal and cholesterol-fed dogs.
Cholesteryl ester-rich beta-very low density lipoproteins (beta-VLDL) are beta-migrating lipoproteins that accumulate in the plasma of cholesterol-fed animals and of patients with type III hyperlipoproteinemia. There are two distinct fractions: fraction I beta-VLDL are chylomicron remnants of intestinal origin, and fraction II beta-VLDL are cholesterol-rich VLDL of hepatic origin. The liver rapidly clears fraction I beta-VLDL from the plasma of both normal and cholesterol-fed dogs. The liver also clears fraction II beta-VLDL rapidly and efficiently from the plasma of normal dogs by receptor-mediated uptake. In cholesterol-fed dogs the clearance is biphasic: an initial rapid die-away of about 30% to 40% of the injected dose within 5 minutes, followed by a slow clearance of plasma radioactivity (a half-life of more than 20 hours). The rapid, initial phase of fraction II beta-VLDL clearance appears to be related to sequestration of the lipoproteins presumably on endothelial cells and is apparently associated with lipolytic processing. Treatment of the fraction II beta-VLDL with lipoprotein lipase abolishes this rapid phase. In the cholesterol-fed dog, the slow, late phase of clearance corresponds to the conversion of fraction II beta-VLDL to the smaller, denser intermediate and low density lipoproteins (IDL and LDL), which are slowly cleared from the plasma. It is concluded that fraction II beta-VLDL are catabolized in the normal dog by rapid uptake mediated at least in part by the apo B,E(LDL) receptor of hepatic parenchymal cells. In cholesterol-fed dogs, in which these receptors are markedly down-regulated, fraction II beta-VLDL are apparently initially bound to endothelial cells and converted to IDL and LDL by lipolytic processing.
Fainaru
M
M
Department of Pathology, University of California, San Francisco.
Funke
H
H
Boyles
J K
JK
Ludwig
E H
EH
Innerarity
T L
TL
Mahley
R W
RW
D000818:Animals; D002791:Cholesterol, Dietary; D004285:Dogs; D008079:Lipoproteins, VLDL / Q000032:analysis / Q000493:pharmacokinetics*; D008099:Liver / Q000378:metabolism; D008297:Male; D011956:Receptors, Cell Surface / Q000378:metabolism; D018110:Receptors, Lipoprotein
D002791:Cholesterol, Dietary; D008079:Lipoproteins, VLDL; D011956:Receptors, Cell Surface; D018110:Receptors, Lipoprotein; C032531:apolipoprotein B,E receptor; C028203:chylomicron receptor