Direct synthesis of low-density lipoprotein apoprotein B in the miniature pig

Abstract

The metabolism of apoprotein B (apo B) was investigated in five miniature pigs following the injection of radiolabeled, very low-density lipoproteins (VLDL). The fractional catabolic rate (FCR) for VLDL apoprotein B was 0.71 +/- 0.10 h-1 (mean +/- SE), the rate of flux was 0.77 +/- 0.05 mg h-1 kg-1, and the pool size of apoprotein B averaged 1.26 +/- 0.20 mg kg-1. Examination of precursor-product relationships between VLDL and low-density lipoprotein (LDL) apoprotein B illustrated that a significant proportion (greater than 80%) of LDL apo B was derived from some source other than VLDL catabolism. In further experiments (n = 4), 125I-VLDL and 131I-LDL were simultaneously injected into miniature pigs. The fractional catabolic rate of LDL apo B averaged 0.055 +/- 0.008 h-1 and the flux rate 0.73 +/- 0.07 mg h-1 kg-1. These dual-label studies allowed us to calculate that an average of 16% of VLDL apoprotein B was converted to LDL and thus the remainder was cleared directly from the circulation. Simultaneous injection of radiolabeled homologous and human VLDL indicated that the catabolism of the two tracers was qualitatively similar. However, human VLDL apo B exhibited a slower fractional catabolic rate (0.42 v 0.71 h-1 P less than 0.05) and reduced rate of conversion to LDL. Therefore, low-density lipoproteins in the pig are largely produced by direct secretion into the circulation, independent of VLDL catabolism. Apo B metabolism in miniature pigs is similar to that of cynomologous and squirrel monkeys, and rats, but differs from normal humans in whom all LDL apo B is derived from VLDL catabolism.