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 (13)C in the
fatty acid moiety. End exhalation breath was collected at intervals after
intravenous injection of the remnant-like
emulsions and analyzed for (13)C 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.