Measurement of expired carbon dioxide to assess the metabolism of remnant lipoproteins.

Abstract

The cholesteryl esters transported from the intestine in chylomicrons are delivered to the liver. Hepatocytes take up chylomicron remnants by receptor-mediated endocytosis and the cholesteryl esters are subsequently degraded. In this study we measured the appearance in breath of labeled carbon dioxide after injection of chylomicron-like emulsions labeled with radioactive cholesteryl [1-14C]oleate. Measurements by the breath test provide an integrated assessment of capacity for clearance and subsequent metabolism of the remnants of the triglyceride-rich lipoproteins. In normal rats, mice, and rabbits injected with the radioactive emulsions, label appeared in the breath after a delay of approximately 30 min, appreciably slower than the appearance of label after injection of emulsions labeled with [14C]triolein or of [14C]oleic acid complexed with albumin. To test for the ability of the procedure to detect defects in remnant clearance, labeled emulsions were injected into diabetic rats, apoE-deficient mice, low density lipoprotein receptor (LDLr)-deficient mice, and Watanabe heritable hyperlipidemic (WHHL) rabbits with defective low density lipoprotein receptors. In rats made diabetic by treatment with streptozotocin the appearance of 14CO2 in breath was slower than in normal control rats. This finding was consistent with previous evidence from our laboratory that remnant clearance is defective in diabetic rats. In LDLr-deficient mice the appearance of 14CO2 was slower when compared with control mice and in apoE-deficient mice the appearance of 14CO2 was extremely small. In homozygous WHHL rabbits, the appearance of 14CO2 in breath was much slower than in normal control rabbits, while in heterozygous WHHL rabbits an intermediate level of appearance was found, consistent with our previous findings of defective remnant clearance in WHHL rabbits. Emulsions with cholesterol omitted, previously found to be cleared from plasma much slower than chylomicron-like emulsions, had much slower appearance of label in breath. The breath test as described is consistent with predicted metabolism of chylomicron remnants and therefore provides a useful means of assessment of remnant catabolism in the intact animal.