A (CO2)-C-13 BREATH TEST TO ASSESS THE METABOLISM OF TRIGLYCERIDE-RICH LIPOPROTEIN REMNANTS IN MICE

Remnant-like emulsions were prepared with lipid compositions similar t o remnants derived from triacylglycerol-rich lipoproteins. When inject ed into the bloodstream of conscious mice the remnant-like emulsions l abeled with cholesteryl[C-13] oleate were metabolized in the liver and the appearance of (CO2)-C-13 in the breath was measured. In control m ice injected with remnant-like emulsions labeled with cholesteryl[C-13 ] oleate, enrichment of (CO2)-C-13 in the breath peaked at 45 min and then decreased markedly by 3 h. In apoE-deficient (-/-) mice no enrich ment was found and in low density lipoprotein receptor (LDLr)-deficien t (-/-) mice the appearance of (CO2)-C-13 in the breath was markedly d ecreased. These findings were consistent with the ability of the breat h test to detect defects in remnant metabolism. The breath test was us eful in detecting a defect in remnant metabolism in LDLr heterozygote (+/-) mice, in which the appearance of (CO2)-C-13 in the breath was le ss by 45 min but remained elevated for the duration of the experiment when compared with control mice. In hepatic lipase-deficient (-/-) mic e no defect in remnant metabolism was found. Under fasting conditions, the enrichment of (CO2)-C-13 in the breath after injection of emulsio n was markedly increased when compared with fed mice, indicating that the metabolism of the injected remnant-like emulsion was probably comp eted for by post-prandial particles under fed conditions. Our findings show that a C-13 breath test can be used to assess the metabolism of remnants. The test provides a useful and sensitive method for non-inva sive testing of remnant metabolism in experimental animals.