A 13CO2 breath test to assess the metabolism of triglyceride-rich lipoprotein remnants in mice

Abstract

Remnant-like emulsions were prepared with lipid compositions similar to remnants derived from triacylglycerol-rich lipoproteins. When injected into the bloodstream of conscious mice the remnant-like emulsions labeled with cholesteryl[13C]oleate were metabolized in the liver and the appearance of 13CO2 in the breath was measured. In control mice injected with remnant-like emulsions labeled with cholesteryl[13C]oleate, enrichment of 13CO2 in the breath peaked at 45 min and then decreased markedly by 3 h. In apoE-deficient (–/–) mice no enrichment was found and in low density lipoprotein receptor (LDLr)-deficient (–/–) mice the appearance of 13CO2 in the breath was markedly decreased. These findings were consistent with the ability of the breath test to detect defects in remnant metabolism. The breath test was useful in detecting a defect in remnant metabolism in LDLr heterozygote (+/–) mice, in which the appearance of 13CO2 in the breath was less by 45 min but remained elevated for the duration of the experiment when compared with control mice. In hepatic lipase-deficient (–/–) mice no defect in remnant metabolism was found. Under fasting conditions, the enrichment of 13CO2 in the breath after injection of emulsion was markedly increased when compared with fed mice, indicating that the metabolism of the injected remnant-like emulsion was probably competed for by post-prandial particles under fed conditions. Our findings show that a 13C breath test can be used to assess the metabolism of remnants. The test provides a useful and sensitive method for non-invasive testing of remnant metabolism in experimental animals.—Martins, I. J., and T. G. Redgrave. A 13CO2 breath test to assess the metabolism of triglyceride-rich lipoprotein remnants in mice.