Abnormal lipid composition of chylomicrons in broad-β disease (type III hyperlipoproteinemia)

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Abstract
Chylomicron (primary particles) were detected by polyvinylpyrollidone (PVP) flocculation in plasma collected after an overnight fast from eight hyperlipemic subjects with broad-β disease (type III hyperlipoproteinemia). The composition of these chylomicrons was abnormal: relatively poor in triglyceride and rich in cholesterol, giving rise to a triglyceride/cholesterol ratio of < 3.0 in all cases, uniformly below the ratio in chylomicrons from eight fasting subjects with mixed lipemia. By contrast, at the peak of alimentary lipemia following an oral fat load (2 g/kg), chylomicrons from broad-β subjects had normal, triglyceride-rich composition (triglyceride/cholesterol = 14.0) and resembled chylomicrons from subjects with mixed lipemia, endogenous lipemia, and familial hypercholesterolemia after similar fat loads. As the alimentary lipemia cleared, chylomicrons remaining in broad-β subjects 14-24 hr after the fat load were again rich in cholesterol. However, a similar degree of cholesterol enrichment was observed in chylomicrons from the subjects with familial hypercholesterolemia, while only a minor increase in cholesterol was recorded in chylomicrons from subjects with mixed or endogenous lipemia. Parallel studies of changes in chylomicron composition during in vitro incubation of whole plasma and of Sf > 400 with Sf < 400 lipoproteins from subjects with the different forms of hyperlipoproteinemia revealed equal cholesterol enrichment of chylomicrons from a subject with mixed lipemia and from a subject with broad-β disease in media of equivalent cholesterol content. These experiments suggested neither excessive avidity of chylomicrons for cholesterol uptake nor excessive influence of Sf < 400 lipoproteins upon chylomicron composition in broad-β disease. Thus, results in this study suggest that the cholesterol-rich chylomicrons observed in subjects with broad-β disease after an overnight fast may originate in the intestine as particles of normal composition (chiefly dietary triglyceride) but assume a composition which is relatively rich in cholesterol through processes of lipolysis and cholesterol transfer among circulating lipoproteins which may not be unique to broad-β disease.