Chylomicron remnant metabolism in familial dyslipidemias studied with a remnant-like emulsion breath test

T.G Redgrave,G.F Watts,I.J Martins,P.H.R Barrett,J.C.L Mamo,S.B Dimmitt,A.D Marais

doi:10.1016/s0022-2275(20)31632-1

Abstract

We have developed a stable isotope breath test for the assessment of chylomicron remnant metabolism and report the results from the breath test in human subjects selected for disorders of chylomicron or remnant metabolism. In type I hyperlipemia, the phenotype is extreme hypertriglyceridemia due to a lack of lipoprotein lipase activity, which causes the failure of remnant formation. The type III dyslipidemia phenotype is caused by the inefficient removal of chylomicron remnants from plasma, generally because of homozygosity for apolipoprotein E2 alleles. The breath test was predicted to be abnormal in type III hyperlipemia, whereas a priori in type I hyperlipemia defective remnant clearance was not anticipated. Subjects were injected with lipid emulsions prepared with a composition similar to normal chylomicron remnants. The emulsions contained cholesteryl ester incorporating the stable nonradioactive isotope 13C in the fatty acid moiety. End exhalation breath was collected at intervals after intravenous injection of the remnant-like emulsions and analyzed for 13C enrichment by isotope-ratio mass spectrometry. Compared with the group of normolipemic men, the fractional catabolic rate of remnants measured by the breath test was significantly decreased (P = 0.006) in subjects with type III dyslipidemia. In the group with type I hyperlipemia, the fractional catabolic rate was not different (P = 0.233) from the control group. Therefore, the underlying capacity for remnant catabolism was normal in this group of markedly hypertriglyceridemic subjects. By short-circuiting the step of lipolysis, the remnant-like emulsion breath test provides direct information about remnant clearance and metabolism, which should assist in investigations of postprandial lipid metabolism.—Redgrave, T. G., G. F. Watts, I. J. Martins, P. H. R. Barrett, J. C. L. Mamo, S. B. Dimmitt, and A. D. Marais. Chylomicron remnant metabolism in familial dyslipidemias studied with a remnant-like emulsion breath test. J. Lipid Res. 2001. 42: 710–715.

Highlights

We have developed a stable isotope breath test for the assessment of chylomicron remnant metabolism and report the results from the breath test in human subjects selected for disorders of chylomicron or remnant metabolism
The triglyceride-rich chylomicrons secreted by the intestine and very low density lipoprotein (VLDL) secreted by the liver are substrates for lipoprotein lipase, which hydrolyzes a proportion of the particle triglyceride content to produce a remnant particle that is smaller in size, contains fewer triglycerides and phospholipids, and is relatively enriched in its content of free and ester cholesterol [5]
The breath test depends on plasma removal of the emulsion remnant particles into the liver for catabolism and on the subsequent metabolism of fatty acids hydrolyzed from the emulsion cholesteryl ester

Summary

Introduction

We have developed a stable isotope breath test for the assessment of chylomicron remnant metabolism and report the results from the breath test in human subjects selected for disorders of chylomicron or remnant metabolism. Compared with the group of normolipemic men, the fractional catabolic rate of remnants measured by the breath test was significantly decreased (P ‫ ؍‬0.006) in subjects with type III dyslipidemia. By short-circuiting the step of lipolysis, the remnant-like emulsion breath test provides direct information about remnant clearance and metabolism, which should assist in investigations of postprandial lipid metabolism.—Redgrave, T. Chylomicron remnant metabolism in familial dyslipidemias studied with a remnant-like emulsion breath test. We report here the results in selected groups of subjects of an investigation of remnant metabolism using a remnant-like emulsion breath test. The new breath test overcomes difficulties in measuring remnant metabolism in humans and is timely because the cholesterol-enriched remnants of triglyceride-rich lipoproteins play a role in accelerated atherosclerosis [2,3,4].

Methods

Results

Conclusion