Intestinal apolipoprotein synthesis and secretion in the suckling pig.

Abstract

The present studies report characterization of intestinal apolipoprotein (apoLp) synthesis and secretion in the suckling pig. Lipoproteins (d less than 1.006 g/ml) from mesenteric lymph were found to contain both apoB-100 and B-48, in addition to apoA-IV, E, A-I, and Cs. Lymph low density lipoproteins (LDL) and high density lipoproteins (HDL) contained mainly apoB-100 and apoA-I, respectively. Analysis of core cholesteryl ester fatty acid composition suggested filtration from plasma as the major source of lymph LDL and HDL. Dual radioisotope labeling of intestinal and hepatic apoLps in lymph, as well as immunoprecipitation of radiolabeled intestinal mucosa, demonstrated intestinal synthesis of apoB-48, A-IV, and A-I. There was no evidence for apoB-100 synthesis by intestinal mucosa. By contrast, piglet liver synthesized apoB-100, E, A-I, and Cs, but not apoB-48. Newly synthesized intracellular intestinal apoA-I was mainly (basic) isoform 1 (pI 5.58), while lymph and plasma HDL apoA-I were predominantly isoform 3 (pI 5.33), mature apoA-I. Lymph apoB (P less than 0.001) and apoA-I (P less than 0.04) mass output increased significantly during lipid absorption. Studies were subsequently conducted in fasting, fat-fed, bile-diverted, and sham-operated animals to determine the role of both dietary and biliary lipid in regulating intestinal apoLp biosynthesis. Proximal and distal small intestinal loops were pulse-radiolabeled with [3H]leucine, and apoB-48 and A-I were immunoprecipitated from cytosolic supernatants. Although a proximal to distal gradient in intestinal synthesis rates for both apoB and A-I was noted in all groups, the acute absorption of dietary lipid did not significantly increase apoB or A-I synthesis in either location. Complete removal of biliary lipid for 48 hr did not alter synthesis rates in jejunum or ileum. These studies suggest that mesenteric lymph apoLps in the suckling pig are derived both by filtration from plasma and by direct secretion from the intestine. Physiologic regulation of intestinal apoA-I and B-48 synthesis rates appears to be independent of luminal lipid availability.