Relative roles of mitochondrial and peroxisomal fatty acid oxidation in the metabolism of chylomicron remnants in rats and mice as assessed by a stable-isotope breath test

We have developed a stable isotope breath test to trace physiological remna nt metabolism. Validity of the test depends on the injected lipid emulsion mimicking chylomicron remnant (CR) clearance and on subsequent metabolism o f the emulsion cholesteryl ester (CE). Oxidation of CE fatty acids could in volve both mitochondrial and peroxisomal pathways. In the present studies v arious agents were used to inhibit the binding of remnants, CE hydrolysis o r mitochondrial fatty acid oxidation. Treatment of mice with suramin or lac toferrin markedly delayed the clearance and metabolism of remnants as shown by the significantly lower enrichment of (CO2)-C-13 in the breath when com pared with untreated mice. In hepatectomized rats injected with remnant-lik e emulsions, enrichment with (CO2)-C-13 was virtually abolished. Treatment of mice with chloroquine or rats with methyl palmoxirate (an inhibitor of m itochondrial fatty acid oxidation) markedly impaired the recovery of label in the breath. Compared with mice fasted overnight, Intralipid by gavage de creased the breath enrichment with (CO2)-C-13 consistent with competition b etween endogenous CR and the injected emulsion particles. These findings sh ow that the breath test reliably measures the metabolism of CR and that CE fatty acid is metabolised by mitochondrial pathways. (C) 2000 Elsevier Scie nce Ireland Ltd. All rights reserved.