Characterization and catabolism of rat very high density lipoproteins.

A previously unrecognized lipoprotein of very high density was isolated from rat serum. During zonal ultracentrifugation of whole serum or of fractions from Sepharose 4B chromatography, a peak comigrating with a peak of cholesterol was found between the typical high density lipoproteins and the residual serum proteins. Centrifugation of chylomicrons, very low density lipoproteins, and high density lipoproteins, radio-iodinated in their lipid and protein moieties and mixed with serum, did not yield this peak. The pooled fractions contained about 85% protein. The remainder was lipid comprising cholesteryl esters, free cholesterol, triglycerides, phosphatidylcholine, and sphingomyelin. Polyacrylamide gel electrophoresis revealed bands in the region of apolipoproteins E and C as the major components. The composition suggested a lipoprotein, and this was substantiated by electron microscopy which showed particles with a mean diameter of 150 A. Their average hydrated density was 1.23 g/ml and the apparent molecular weight was 1.35 X 10(6). These very high density lipoproteins are characterized by a rapid catabolism as compared to high density lipoproteins. Within 10 min, 84% and 70% of intravenously injected 125I-labeled very high density lipoproteins were removed from plasma of male and female rats, respectively, and did not appear to be converted to lipoproteins of a different density class. Ninety-five percent of the removed 125I was recovered in the liver and the radioactivity per gram of tissue was also highest for the liver. Accordingly, the rate of clearance of 125I-labeled very high density lipoproteins was markedly reduced in functionally eviscerated rats. Radioautography revealed that most of the silver grains representing very high density lipoproteins were associated with hepatocytes and only about 1% was found over v. Kupffer cells. Uptake and degradation by freshly isolated rat hepatocytes were mediated by a saturable and specific binding site. Composition and metabolic pathway are compatible with a function of very high density lipoproteins in the transport of protein and lipids to the liver.