Abstract
Levels of plasma very low density lipoprotein (VLDL) and low density lipoprotein (LDL) constituents increase with age. In an attempt to further define the mechanisms responsible for these changes, kinetic studies of VLDL and LDL apolipoprotein (apo) B-100 were carried out in 19 normolipidemic male subjects with plasma total cholesterol and triglyceride levels below the 90th percentile whose ages ranged from 24 to 73 years. Subjects were maintained on standardized diets consisting of 47-49% of calories as carbohydrate, 15% protein, and 36-40% fat (15-17% saturated, 15-17% monounsaturated, 6% polyunsaturated) with 150 mg cholesterol/1000 kcal. At the end of the diet period, the metabolism of apoB-100 within VLDL, intermediate density lipoprotein (IDL), and LDL was studied in the fed state using a primed-constant infusion of [2H3]leucine. Data were fit to a multicompartmental model to determine residence times and production rates of apoB-100 in each fraction. There were significant positive correlations between age and VLDL, IDL, and LDL apoB-100 concentrations (r = 0.50, 0.62, and 0.69; P = 0.03, 0.004, and 0.001, respectively). There was a positive correlation between age and the production rate of VLDL apoB-100 (r = 0.50, P = 0.03), but there was no significant relationship between age and either IDL or LDL apoB-100 production rates. Age was also positively correlated with the residence time of LDL apoB-100 (r = 0.68 P = 0.001). Our data suggest that the age-associated increase in VLDL apoB-100 is due to an increased production rate of this constituent, whereas the age-associated increase in LDL apoB-100 is due to an increased residence time of these particles in plasma.
Highlights
Low Medium High1 x 106 1 x 106 1 x 106 1 x 1062 x 103 3 x 103 5.2 x 103 10.2 x 103"Calculated as in reference 18.'As calculated in the current study.were analyzed with the CONSAM 30 software program [19]
There was a substantial improvement in the sum of the fractional standard deviation (FSD) by including one dummy data point in each of the very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) data sets
The results of this study indicate that the residence time of LDL apoB-100 decreases with advancing age in men
Summary
Low Medium High1 x 106 1 x 106 1 x 106 1 x 1062 x 103 3 x 103 5.2 x 103 10.2 x 103"Calculated as in reference 18.'As calculated in the current study.were analyzed with the CONSAM 30 software program [19]. Two dummy data points, representing the theoretical maximal enrichment, referred to as the plateau value, of apoB-100, calculated as previously described [13], were inserted into each data set at 350 and 400 h to ensure that the VLDL, IDL, and LDL data sets all reached an identical plateau value and to improve the reproducibility of the analysis. The mass of each lipoprotein fraction was accounted for in the model by dividing the sum of the function(s) describing the kinetic behavior of each lipoprotein fraction by the corresponding apoB-100 pool size (equation 1). This is identical to fitting data expressed as tracer units to these same function(s) (equation 2)
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