ENHANCED HEPATIC-UPTAKE AND METABOLISM OF DESIALYLATED CHYLOMICRONS

Background and Aim: The uptake and metabolism of desialylated chylomic rons were compared with that of untreated chylomicrons and chylomicron remnants in the perfused liver and in vivo in the rat. Methods and Re sults: After treatment with neuraminidase, desialylated chylomicrons d id not differ in either lipid or apolipoprotein composition from untre ated chylomicrons. In 90 minutes, the perfused liver took up 25.1% of [14C]palmitate-labelled chylomicrons, whereas in the same period 42.4% of labelled desialylated chylomicrons were taken up compared with 49. 1% of labelled chylomicron remnants Hepatic metabolism was measured by oxidation of the labelled fatty acid to (CO2)-C-14 and conversion of [14C]triacylglycerol to phospholipid. Metabolism of untreated chylomic rons was minimal (0.8% and 3.6% respectively) whereas oxidation of des ialylated chylomicrons rose to 2.0% compared to 2.21% for remnants and conversion to phospholipid amounted to 15.3% for the desialylated chy lomicrons compared to 16.1% for remnants. After intravenous administra tion of [3H]cholesterol-labelled untreated chylomicrons to rats in viv o, 75.4% remained in the circulation after 10 min, compared to only 37 .0% for desialylated chylomicrons and 27.5% for chylomicron remnants. Most of this uptake was accounted for by the liver. Over a 3 h period except for the first 20 minutes, the disappearance curves for both unt reated and desialylated chylomicrons in blood were virtually superimpo sable, with 20% of the administered radioactivity remaining after I h. Secretion of[3H]radioactivity into bile was linear after 30 minutes a nd there were no significant differences between untreated and desialy lated chylomicrons, with 11-12% of the administered radioactivity bein g present in the bile after 3 h, of which 70-80% was in bile acids and the remainder in unesterified cholesterol. Conclusion: The results pr ovide evidence that desialylation of chylomicrons increases their rate of removal by the liver and that the uptake is also accompanied by co mparable increases in their metabolism, which cannot be distinguished from that of chylomicron remnants. Uptake of desialylated chylomicrons via the asialoglycoprotein receptor would appear to be an alternative mechanism for clearance of chylomicrons when the normal pathways for chylomicron metabolism via remnant formation and the low-density lipop rotein or remnant receptor are deficient. (C) 1997, Medikal Press.