Intestinal apoB synthesis, lipids, and lipoproteins in chylomicron retention disease.

Chylomicron retention disease is characterized by fat malabsorption, hypocholesterolemia, normal fasting triglycerides, and marked intestinal steatosis despite the presence of both plasma and intestinal apoprotein B. The defect remains unknown but presumably involves the synthesis or secretion of chylomicrons. The present investigation examines this hypothesis by studying the biosynthesis of chylomicrons in cultured jejunal explants and by defining the quantitative and qualitative abnormalities of plasma lipids and of circulating lipoproteins. Following 2-3 years of a low fat diet supplemented with medium chain triglycerides, six patients with chylomicron retention disease had significantly higher triglyceride (TG) levels coupled with a decrease in both free (FC) and esterified cholesterol (EC) as well as in essential fatty acids and phospholipids (PL) when compared to healthy controls. The low total plasma cholesterol was largely accounted for by low levels of both low density (LDL) and high density lipoprotein (HDL) cholesterol. VLDL and LDL were characterized by a diminished percentage of CE with an increase of TG while HDL contained relatively more FC as well as PL and less CE. The diameter of VLDL was larger whereas those of LDL and HDL were smaller than in normal controls. Jejunal explants, when incubated with [14C]palmitate, were capable of normal biosynthesis of TG, diglycerides, PL, and CE. These lipids, however, except for PL, were retained in the tissue and could not be secreted into the culture medium. Incubation of intestinal biopsies with [3H]leucine and [14C]mannose resulted in normal protein synthesis and reduced glycosylation. The presence of intestinal apoB-48 was confirmed by immunoblot using 2D8 antibodies. These data suggest that the intestinal defect in this disease results from a disorder of the final assembly of chylomicrons or in the mechanism of their exocytosis.