MEASUREMENT OF EXPIRED CARBON-DIOXIDE TO ASSESS THE METABOLISM OF REMNANT LIPOPROTEINS

The cholesteryl esters transported from the intestine in chylomicrons are delivered to the liver. Hepatocytes take up chylomicron remnants b y receptor-mediated endocytosis and the cholesteryl esters are subsequ ently degraded. in this study we measured the appearance in breath of labeled carbon dioxide after injection of chylomicron-like emulsions l abeled with radioactive cholesteryl [1-C-14]oleate. Measurements by th e breath test provide an integrated assessment of capacity for clearan ce and subsequent metabolism of the remnants of the triglyceride-rich lipoproteins. In normal rats, mice, and rabbits injected with the radi oactive emulsions, label appeared in the breath after a delay of appro ximately 30 min, appreciably slower than the appearance of label after injection of emulsions labeled with [C-14]triolein or of [C-14]oleic acid complexed with albumin. To test for the ability of the procedure to detect defects in remnant clearance, labeled emulsions were injecte d into diabetic rats, apoE-deficient mice, low density lipoprotein rec eptor (LDLr)-deficient mice, and Watanabe heritable hyperlipidemic (WH HL) rabbits with defective low density lipoprotein receptors. In rats made diabetic by treatment with streptozotocin the appearance of (CO2) -C-14 in breath was slower than in normal control rats. This finding w as consistent with previous evidence from our laboratory that remnant clearance is defective in diabetic rats. In LDLr-deficient mice the ap pearance of (CO2)-C-14 was slower when compared with control mice and in apoE-deficient mice the appearance of (CO2)-C-14 was extremely smal l. In homozygous WHHL rabbits, the appearance of (CO2)-C-14 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 rab bits. Emulsions with cholesterol omitted, previously found to be clear ed from plasma much slower than chylomicron-like emulsions, had much s lower appearance of label in breath. The breath test as described is c onsistent with predicted metabolism of chylomicron remnants and theref ore provides a useful means of assessment of remnant catabolism in the intact animal.-Redgrave, T. G., I, J, Martins, and B-C, Mortimer. Mea surement of expired carbon dioxide to assess the metabolism of remnant lipoproteins.