Catabolism of Very Low Density Lipoprotein B Apoprotein in Man

Abstract

A B S T R A C a The turnover and the catabolic fate of the B apoprotein of very low density lipoprotein (VLDL-B) was studied in 15 normal and hyperlipidemic subjects using reinjected autologous VLDL labeled with radioiodine. The specific radioactivity-time curve ofthe B apoprotein in total VLDL (Sf 20-400) was multiexponential but conformed to a two-pool model during the first 48 h of catabolism. The flux was highest in several hypertriglyceridemic subjects. The mass of pool A exceeded the intravascular content of VLDL-B by 30% on average, indicating extravascular metabolism of VLDL. The two-pool model might reflect the input of several populations of particles or heterogeneity of catabolic processes or pools. The flux of B apoprotein was also measured in several subclasses of VLDL, in smailler intermediate density lipoproteins, and in low density lipoproteins (LDL). In three subjects the flux was similar in Sf 60-400 and in Sf 12-60 lipoproteins, suggesting that VLDL was catabolized at least to a particle in the density range Sf 12-60. Subsequent catabolism appeared to proceed by two pathways: in normotriglyceridemiic subjects, B apoprotein flux in the Sf 20-400 and in Sf 12-20 lipoproteins was similar, whereas in hypertriglyceridemic subjects flux through Sf 12-20 accounted for only part of the VLDL-B flux.The flux of low density' lipoprotein B apoprotein (LDL-B), which is believed to be derived from VLDL catabolism, was calculated f'rom the area between the specific activity time curves of' VLDL-B and LDL-B. In subjects with normal plasmla triglyceride concentration, LDL-B flux was froml 91% to 113% of that of VLDL-B; but in three hy'pertriglyceridemic subjects showing high rates of VLDL-B transport, LDL-B flux was only one-third that of VLDL-B. This suggests that

Transport of Very Low Density Lipoprotein Triglycerides in Varying Degrees of Obesity and Hypertriglyceridemia

“…This possibility has been invoked by other workers (50,51) including a preliminary report using the same methodology as employed in this work (52). Second, the "remnant" of VLDL may be removed by pathways other than conversion to LDL, particularly in hyperlipidemic subjects, as suggested for man by the work of Sigurdssoni et al (49), Reardlon et al (15), and Bermlani et al (53), anid for rats by Faergeman et al (54).…”

“…They assumed that for the remaining patients single-exponential analysis should provide a reasonable approximation. It should be emphasized that in most of these previous studies, decay curves were followed for only [12][13][14][15][16][17][18] h, whereas the departure from log-linear decay is often not readily apparent until later times.…”

Measurement of very low density and low density lipoprotein apolipoprotein (Apo) B-100 and high density lipoprotein Apo A-I production in human subjects using deuterated leucine. Effect of fasting and feeding.

“…Subjects have therefore been studied during periods of both fasting and feeding. In previous VLDL apo B kinetic studies (26)(27)(28)(29)(30), fat-and calorie-restricted diets have been given to minimize the secretion of chylomicrons and VLDL from the intestine. This rather artificial situation, however, represents neither a fasted nor fed state.…”

Transfers and exchanges of esterified cholesterol between plasma lipoproteins

“…The major proportion of the LCAT-derived esterified cholesterol in human plasma is transferred from HDL to other lipoprotein fractions, predominantly (in mass terms) to VLDL (Nichols & Smith, 1965). Under normal conditions human VLDL are not removed from the plasma, but as a consequence of catabolism within the plasma are converted quantitatively to LDL (Reardon et al, 1978) which are taken up by tissues (Goldstein & Brown, 1974). In a normal human subject with an LDL esterified cholesterol concentration of 2000-3000nmol/ml and an LDL removal rate in vivo of about 2% per hour (Langer et al, 1972) a tissue uptake of LDL can account for the removal of 40-60nmol of esterified cholesterol/h per ml, representing the major proportion of that formed in the LCAT reaction.…”