Characterization of chylomicron remnant clearance by retinyl palmitate label in normal humans

To characterize chylomicron remnant clearance by the liver, plasma elimination of retinyl palmitate-labeled chylomicron remnants was studied in 18 healthy subjects, ages 21-42 years. Autologous plasma containing retinyl palmitate-labeled chylomicrons and their remnants was injected intravenously, and retinyl palmitate disappearance was measured in serial plasma samples in all subjects and in lipoprotein fractions in 11 subjects. The injected doses (n = 18) ranged from 0.34 to 7.11 mumol retinyl palmitate in d less than or equal to 1.006 g/ml particles with an average molar ratio of 330/1 of retinyl palmitate/apoB-48 (n = 8). The label distributed in the intravascular space and exhibited apparent first order elimination, monoexponential in 6 and biexponential in 12 subjects. The first rapid component k1 (t1/2 18.8 +/- 11.4 min, n = 18) was shown to represent retinyl palmitate in particles of d less than or equal to 1.006 g/ml, i.e., chylomicron remnants, and the second slow component k2 (t1/2 123 +/- 62 min, n = 12) small amounts of retinyl palmitate (11 +/- 7%) injected in d greater than 1.006 g/ml particles (therefore excluded from analysis). Assuming a single-compartment model, initial rates of elimination (= dose x k1) of labeled chylomicron remnants obeyed (P = 0.06) Michaelis-Menten saturation kinetics: Km was 921 +/- 305 nmol retinyl palmitate label and Vmax 124 +/- 14 nmol/min corresponding to 0.88 nM apoB-48 for Km and 0.25 x 10(-3) nmol apoB-48.min-1.g-1 liver for Vmax. Their elimination was limited neither by the injected triglyceride dose nor theoretically by the liver blood flow. After the intake of 70 g of fat (cream) containing retinyl palmitate, the plasma retinyl palmitate concentration exceeded the estimated saturation concentration for 7 h. In conclusion, physiological chylomicron remnant catabolism by the liver appears to be saturable by ordinary lipid intake in healthy humans.