Metabolism of canine β-very low density lipoproteins in normal and cholesterol-fed dogs

Abstract

Cholesteryl ester-rich β-very low density lipoproteins (β-VLDL) are β-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 β-VLDL are chylomicron remnants of intestinal origin, and fraction II β-VLDL are cholesterol-rich VLDL of hepatic origin. The liver rapidly clears fraction I β-VLDL from the plasma of both normal and cholesterol-fed dogs. The liver also clears fraction II β-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 β-VLDL clearance appears to be related to sequenstration of the lipoprotein presumably on endothelial cells and is apparently associated with lipolytic processing. Treatment of the fraction II β-VLDL with lipoprotein lipase abolishes this rapid phase. In the cholesterol of fraction II β-VLDL to the smaller, denser intermediate and low density lipoprotein (IDL and LDL), which are slowly cleared from the plasma. It is concluded that fraction II β-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 β-VLDL are apparently initially bound to endothelial cells and converted to IDL and LDL by lipolytic processing.