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 remnant metabolism. Validity of the test depends on the injected lipid emulsion mimicking chylomicron remnant (CR) clearance and on subsequent metabolism of the emulsion cholesteryl ester (CE). Oxidation of CE fatty acids could involve both mitochondrial and peroxisomal pathways. In the present studies various agents were used to inhibit the binding of remnants, CE hydrolysis or mitochondrial fatty acid oxidation. Treatment of mice with suramin or lactoferrin markedly delayed the clearance and metabolism of remnants as shown by the significantly lower enrichment of 13CO(2) in the breath when compared with untreated mice. In hepatectomized rats injected with remnant-like emulsions, enrichment with 13CO(2) was virtually abolished. Treatment of mice with chloroquine or rats with methyl palmoxirate (an inhibitor of mitochondrial fatty acid oxidation) markedly impaired the recovery of label in the breath. Compared with mice fasted overnight, Intralipid by gavage decreased the breath enrichment with 13CO(2) consistent with competition between endogenous CR and the injected emulsion particles. These findings show that the breath test reliably measures the metabolism of CR and that CE fatty acid is metabolised by mitochondrial pathways.
Martins
I J
IJ
Department of Physiology, The University of Western Australia, Stirling Highway, Nedlands, Perth, Australia. imartins@cyllene.uwa.edu.au
Vermeulen
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D000284:Administration, Oral; D000818:Animals; D001944:Breath Tests / Q000379:methods; D002245:Carbon Dioxide / Q000032:analysis; D002247:Carbon Isotopes; D002738:Chloroquine / Q000494:pharmacology; D002788:Cholesterol Esters / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D004852:Epoxy Compounds / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage; D005227:Fatty Acids / Q000378:metabolism*; D006498:Hepatectomy; D006868:Hydrolysis; D007781:Lactoferrin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism*; D010084:Oxidation-Reduction; D020675:Peroxisomes / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D013498:Suramin / Q000494:pharmacology
D002247:Carbon Isotopes; D002788:Cholesterol Esters; D002914:Chylomicrons; D004852:Epoxy Compounds; D005217:Fat Emulsions, Intravenous; D005227:Fatty Acids; D011422:Propionates; D002245:Carbon Dioxide; D013498:Suramin; D002738:Chloroquine; D007781:Lactoferrin; C017522:methyl 2-tetradecylglycidate