Abstract

Although editing of apolipoprotein (apo)B in the small intestine, yielding apoB-48, is thought to be nearly complete in adult humans, small amounts of intestinal apoB-100 may also be produced. We have evaluated the fraction of unedited apoB secreted from the intestine postprandially in subjects with primary combined hyperlipidemia, a disorder in which secretion of apoB-100 into the blood is increased. Three hours after these subjects and healthy controls were fed a fat-rich meal containing retinol, the distribution of retinyl esters (RE) between plasma triglyceride-rich lipoprotein (TRL) fractions containing apoB-100 and apoB-48 was measured under conditions minimizing transfer of RE between lipoprotein particles. The estimated maximal percentage of unedited intestinal apoB-100 (∼3%) was not increased in subjects with primary combined hyperlipidemia, suggesting that reduced editing of intestinal mRNA does not contribute to the pathogenesis of this disorder. Postprandially, the triglyceride content of TRL containing apoB-48 more than doubled, leading to a 20% increase in mean diameter, yet the surface concentration of phospholipids and soluble apolipoproteins (apoE and total apoC) was unchanged. Furthermore, the surface concentrations of these components did not differ among TRL containing apoB-48 and two smaller fractions of apoB-100 TRL with distinct immunoreactivities.These findings suggest that available surface area is a major determinant of the particle content of each of these surface components of TRL species of differing size and origin.

Highlights

  • Editing of apolipoproteinB in the small intestine, yielding apoB-48, is thought to be nearly complete in adult humans, small amounts of intestinal apoB-100 may be produced

  • 55%, 80%, and 70% of the increment in triglyceride-rich lipoprotein (TRL)-total cholesterol (TC), TG, and PL was in the apoB-48-rich fraction, all of which increased significantly, as did TG in the bound fraction of apoB-100 TRL

  • Our findings provide in vivo evidence that the human intestine secretes a small but measurable fraction of apoB100 in TRL, both in healthy adults and in those with primary combined hyperlipidemia

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Summary

Introduction

Editing of apolipoprotein (apo)B in the small intestine, yielding apoB-48, is thought to be nearly complete in adult humans, small amounts of intestinal apoB-100 may be produced. We have evaluated the fraction of unedited apoB secreted from the intestine postprandially in subjects with primary combined hyperlipidemia, a disorder in which secretion of apoB-100 into the blood is increased. Three hours after these subjects and healthy controls were fed a fat-rich meal containing retinol, the distribution of retinyl esters (RE) between plasma triglyceride-rich lipoprotein (TRL) fractions containing apoB-100 and apoB-48 was measured under conditions minimizing transfer of RE between lipoprotein particles.

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