Relative contributions by liver and intestine to individual plasma apolipoproteins in the rat.

Abstract

In order to determine if plasma apolipoproteins could be synthesized by tissues other than liver and intestine, two known sites of lipoprotein biogenesis, r3H]leucine incorporation into lipoproteins was measured in rats in which the small intestine was resected and the liver was removed from the circulation. No evidence for additional apolipoprotein sources was found. Two methods were then developed to determine the relative contributions of liver and intestine to individual apolipoproteins found in plasma. In one method, plasma proteins from liver and intestine were differentially labeled by the simultaneous administration of r3H]leutine intraduodenally and [‘4C]leucine intraportally. The relative organ contributions were calculated from the 3H/14C ratios measured in individual plasma apolipoproteins and in several reference proteins, plasma albumin and selected apolipoproteins from mesenteric lymph. In the second method, the patterns of apolipoprotein synthesis were determined in (a) isolated, perfused livers, (b) isolated intestinal segments in uIuo, and (c) intact rats, respectively, from the distribution of incorporated [3H]leucine in each preparation. The relative organ contributions required to account for the pattern observed in the intact animal were then calculated by multiple regression analysis. Results from the two complementary methods, both applied in fat-fed animals, were in good agreement. The quantitative order of apolipoprotein synthesis in intact rats was apolipoprotein E (ape-E) > apo-B > apoA-I > apo-C > apo-A-IV. Nineteen per cent of the total apolipoprotein pool was synthesized by intestine and 81% by liver. The per cent intestinal contribution to individual proteins was as follows: apo-A-IV, 59; apoA-I, 56; apo-B, 16; apo-C-II, 10; apo-C-III-O, 7; apo-CI&2(-1), ~10; apo-C-III-3, 4; and apo-E, 4. Apo-C-I analyses were uncertain, but little or none was derived from intestine. Since apo-A-I and apo-A-IV are major proteins in plasma high density lipoproteins, intestine contributes importantly to this lipoprotein class.