Journal of Lipid Research, Vol. 20, 316-324, March 1979
Copyright © 1979 by Lipid Research, Inc.

Quantification of the hepatic contribution to the catabolism of high density lipoproteins in rats

Gunnar Sigurdsson , Simon-Pierre Noel , and Richard J. Havel

Cardiovascular Research Institute and Department of Medicine, University of California, San Francisco, CA 94143

Isolated rat livers were perfused for four hours in a recirculating system containing washed rat erythrocytes. Biologically screened radioiodinated rat high density lipoproteins (1.090 < d < 1.21 g/ml) were added to the perfusate with different amounts of whole serum to supply unlabeled rat high density lipoproteins. The protein moiety of the lipoprotein contained more than 95% of the radioiodine. The fraction of apolipoprotein mass degraded during the perfusion was quantified by the linear increment of non-protein-bound radioiodine in the perfusate, corrected for the increment observed during recirculation of the perfusate in the absence of a liver. The small amount of ¹³¹I secreted into bile was added to calculate the fractional catabolic rate. The fractional catabolic rate ranged from 0.22 to 0.63% per hour in 12 experiments and was inversely related to the size of the perfusate pool of high density apolipoprotein. The absolute catabolic rate of high density apolipoprotein (fractional catabolic rate x pool size) in three livers in which the concentration of rat HDL in the perfusate approximated that in intact rats was 69.5 ± 10.4 µg hr^-1 (mean ± SD). The rate of disappearance of cholesteryl esters of rat high density lipoproteins (labeled biologically by injecting donor rats with [5-³H]mevalonic acid) from the liver perfusate did not exceed that of the apoprotein component. These rates were compared with catabolic rates for rat high density lipoproteins in intact rats. Fractional catabolic rate in vivo, obtained by multicompartmental analysis of the disappearance curve of ¹³¹I-high density apolipoprotein from blood plasma, was 11.9 ± 1.3% hr^-1 (mean ± SD). Total catabolic rate in vivo (fractional catabolic rate x intravascular pool of high density apolipoprotein) was 986 ± 145 µg hr^-1 (mean ± SD). The results suggest that only a small fraction of high density lipoproteins in blood plasma of rats is degraded directly by the liver.—Sigurdsson, G., S-P. Noel, and R. J. Havel. Quantification of the hepatic contribution to the catabolism of high density lipoproteins in rats.

Supplementary key words HDL apoproteins • cholesteryl esters • fractional catabolic rate

Submitted on February 15, 1978
Accepted on September 5, 1978

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