Discrepancies in the catabolic pathways of rat and human low density lipoproteins as revealed by partial hepatectomy in the rat

Abstract

The serum decay of iodine-labeled low density lipoprotein (LDL) was measured in rats 2–8 h after partial hepatectomy or sham-operation. In sham-operated rats homologous LDL showed a biexponential decay with t 1 2 ' s of 0.27 ± 0.02 h and 4.3 ± 0.8 h for the initial rapid phase and the slow phase, respectively. After partial hepatectomy the t1/2 of the rapid phase was unchanged, while the t 1 2 of the slow phase increased to 10.3 ± 1.0 h ( P < 0.01). The fractional catabolic rate (F.C.R.) was decreased by 62% (from 4.8 ± 0.9 to 1.8 ± 0.2/day), a % comparable to the amount of liver removed. The level of serum LDL is slightly elevated (19%), if measured 8 h after partial hepatectomy. Chemical analysis shows that the triglyceride content of LDL decreases from 9.4 ± 2.3% in control rats to 3.7 ± 0.9% after partial hepatectomy. Human iodine-labeled LDL shows a monoexponential decay from rat serum with a t sol1 2 of 9.4 ± 0.7 h, which is not affected by partial hepatectomy. The F.C.R. is low in both sham-operated and hepatectomized rats (1.8 ± 0.1 vs. 1.9 ± 0.1/day). The % of the injected rat LDL radioactivity recovered in the liver of control rats is twice as high as that of human LDL, as measured 6 h after the injection; at this time the serum radioactivity is much lower in the case of rat LDL. Partial hepatectomy did not change the levels of extrahepatic tissue radio-activities significantly. It is concluded that the liver determines the catabolic rate of homologous LDL-apoproteins in the rat. In contrast, the slow degradation of human LDL-apoprotein is probably located extrahepatically.