Delayed clearance of chylomicron remnants following vitamin-A-containing oral fat loads in broad-beta disease (type III hyperlipoproteinemia).

Abstract

Chylomicron "remnants" are formed by the selective removal of triglyceride catalyzed by lipoprotein lipase. To investigate a possible defect in the clearance of these remnants in the pathophysiology of broad-beta disease (type III hyperlipoproteinemia), subjects with this disorder and comparison subjects with endogenous hypertriglyceridemia (and type IV lipoprotein patterns) ingested an oral fat load (corn oil: cocoa butter, 1:1, 50 g/sq M) containing retinyl ester, 100 mg, with or without 15 muCi 15-(14) C-retinol (43.7 mCi/mg). The content of triglyceride and vitamin A was sequentially determined in chylomicrons (Sf more than 400) and very low density lipoproteins (VLDS, Sf20-400) over the ensuing 24-72 hr. Vitamin A was chosen as a marker for exogenous sterol assimilation since, like cholesterol, it is absorbed in the small intestine and cosecreted in esterified form with triglyceride in the chylomicron core; however, unlike cholesterol, once having been removed by the liver, it cannot be recycled inot VLDL, but subsequently circulates only as a complex with the high density retinol binding protein. Thus measurements of the vitamin A/triglyceride ratio in Sf greater than 20 lipoproteins reflected the relative efficiency of vitamin A versus triglyceride removal within these lipoproteins. These studies confirmed the intital concentration of exogenous vitamin A in chylomicrons but invariably disclosed an increasing proportion of the remaining Sf greater than 20 vitamin A in VLDL 24 hr after its ingestion. The vitamin A/triglyceride ratio also invariably increased between 6 and 24 hr in the Sf20-30 subfraction, reflecting the formation of vitamin A-rich "remnants" as intermediate species in the catabolism of chylomicrons and VLDL. Among those with mild to moderate endogenous hypertriglyceridemia the Sf greater than 400 vitamin A/triglyceride ratio declined between 6 and 24 hr, reflecting the efficient passage of the vitamin A through this fraction and/or continued secretion of Sf greater than 400 particles rich in triglyceride. Among those with severe endogenous hypertriglyceridemia, both the peak and decline in the Sf greater than 400 vitamin A/triglyceride ratio were delayed. However, among those with broad-beta disease, an increasing vitamin A/triglyceride ratio between 6 and 24 hr was frequent within all VLDL subfractions and invariable among lipoproteins of Sf greater than 400 regardless of the degree of antecedent hypertriglyceridemia. Although additional experiments disclosed a similar delay in both vitamin A and triglyceride assimilation when basal triglyceride levels were high in these subjects, marked reduction of triglyceride levels did not correct the rise in the Sf greater than 400 vitamin A/triglyceride ratio between 6 and 24 hr. Experiments employing preparative electrophoresis confirmed the identity of VLDL containing a high vitamin A/triglyceride ratio with the beta-VLDL which accumulate in broad-beta disease...

• Authors: W R Hazzard, E L Bierman
• Journal: Metabolism: clinical and experimental (Metabolism) Vol. 25 Issue 7 Pg. 777-801 (Jul 1976) ISSN: 0026-0495 [Print] United States
• PMID: 181657 (Publication Type: Clinical Trial, Comparative Study, Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Chylomicrons
• Fats
• Lipoproteins, LDL
• Lipoproteins, VLDL
• Triglycerides
• Vitamin A

Topics

• Adult
• Aged
• Chylomicrons (metabolism)
• Clinical Trials as Topic
• Fats (metabolism)
• Female
• Humans
• Hyperlipidemias (metabolism)
• Lipoproteins, LDL (blood)
• Lipoproteins, VLDL (blood, metabolism)
• Liver (metabolism)
• Male
• Middle Aged
• Triglycerides (blood)
• Vitamin A (metabolism)