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Journal of Lipid Research, Vol. 42, 710-715, May 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

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

Correspondence to: T. G. Redgrave, at the Department of Physiology, the University of Western Australia, Stirling Hwy, Nedlands, Perth, Western Australia 6907. e-mail redgrave@cyllene.uwa.edu.au

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.

Supplementary key words: hyperlipidemia, isotope ratio mass spectrometry, carbon isotopes, cholesteryl ester

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