Chylomicron metabolism in normal, cholesterol-fed, and Wantanabe heritable hyperlipidemic rabbits: saturation of the sequestration step of the remnant clearance pathway

• Published in: The Journal of biological chemistry Vol. 270; no. 15
• Main Authors: Hussain, M.M. (Medical College of Pennsylvania, Philadelphia, PA.), Innerarity, T.L, Brecht, W.J, Mahley, R.W
• Format: Journal Article
• Language: English
• Published: 14.04.1995
• Subjects: ANTICORPS MONOCLONAL; ANTICUERPOS MONOCLONALES; CHOLESTEROL; CHYLOMICRON; COLESTEROL; CONEJO (ORYCTOLAGUS); DIETA; DISTRIBUCION ECONOMICA; DISTRIBUTION ECONOMIQUE; HIPERLIPIDEMIA; HYPERLIPIDEMIE; LAPIN (ORYCTOLAGUS); LIPOPROTEINAS; LIPOPROTEINE; METABOLISME DES LIPIDES; METABOLISMO DE LIPIDOS; PLASMA SANGUIN; PLASMA SANGUINEO; QUILOMICRONES; REGIME ALIMENTAIRE; TECHNIQUE DES TRACEURS; TECNICAS DE TRAZADORES; TEJIDOS ANIMALES; TISSU ANIMAL; TRASTORNOS GENETICOS; TROUBLE GENETIQUE
• ISSN: 0021-9258; 1083-351X

The plasma clearance of radiolabeled chylomicrons was compared in normal, cholesterol-fed, and Watanabe heritable hyperlipidemic (WHHL) rabbits. Chylomicron clearance was rapid in normal rabbits but was significantly retarded in cholesterol-fed and WHHL rabbits. At 40 min after the injection of chylomicrons, 14-17% of the injected dose remained in the plasma of normal rabbits, whereas approximately 40-50% of the injected dose remained in the plasma of cholesterol-fed and WHHL rabbits. The differences were reflected in the reduced plasma clearance by the liver and bone marrow of the cholesterol-fed and WHHL rabbits. The hyperlipidemic rabbits expressed normal levels of low density lipoprotein (LDL) receptor-related protein/alpha2-macroglobulin receptor in the liver. In contrast, the hepatic levels of LDL receptors were lower in hyperlipidemic rabbits; as expected, they were significantly lower in WHHL rabbits compared with normal and cholesterol-fed rabbits. Furthermore, it was demonstrated that lipoproteins accumulating in the plasma of the hyperlipidemic rabbits competed for and retarded the clearance of chylomicrons from the plasma. Competition was demonstrated by cross-circulation of normal and cholesterol-fed or normal and WHHL rabbits, in which the rapid influx of plasma containing the accumulated plasma lipoproteins from cholesterol-fed or WHHL rabbits was shown to impair the uptake of chylomicrons by the liver and bone marrow of normal rabbits. These observations were extended by infusing isolated lipoproteins into normal rabbits. The rabbit d 1.02 g/ml (remnant) fraction and the canine cholesterol-rich high density lipoproteins (HDL) with apolipoprotein E (HDLc) inhibited chylomicron clearance, whereas human LDL and HDL from humans and rabbits did not. We conclude that the low LDL receptor activity in the cholesterol-fed and WHHL rabbits may contribute, at least in part, to the impaired clearance by decreasing remnant uptake