Three-pool model of the long-term turnover of plasma cholesterol in man

Abstract

The long-term turnover of plasma cholesterol was examined in six men injected intravenously with [4-(14)C]cholesterol. The specific radioactivity-time curves were determined for periods of 32-41 wk and were analyzed by computer according to a two-pool and to a three-pool model. In each subject, the three-pool model provided a significantly better description of the long-term turnover curve than did the two-pool model. No further improvement in fit between observed and computed curves was obtained with a four-pool model. The results indicate that the turnover curves of all six subjects conformed to, and could be satisfactorily described by, a three-pool model, as expressed by the equation: specific activity = A(1)e(-alpha(1)t) + A(2)e(-alpha(2)t) + A(3)e(-alpha(3)t). The assumption was made that exit of cholesterol from the body occurs only by way of the tissue pools which comprise the rapidly exchangeable compartment, pool 1. With this assumption, the production rate in pool 1 (PR) is equivalent to the total body turnover rate. The parameters of the three-pool model which can be calculated include PR, the size of pool 1 (M(1)), and the rate constants for transfer between pools. Unique values cannot be obtained for the sizes of the more slowly exchangeable pools of body cholesterol, but their upper and lower limiting values can be determined. The observed values for PR and M(1) (means +/- sem) were 1.13 +/- 0.09 g/day and 23.4 +/- 1.1 g, respectively. When only the first 12 wk of data were analyzed, the turnover curves in all subjects conformed to the two-pool model. The results so obtained were compared with those obtained with the long-term data. The medium-term data provided a valid estimate for M(1), a slightly (8-9%) elevated value for PR, and a quantitatively unreliable (low) estimate of total exchangeable body cholesterol, as compared with the long-term data. Previous estimates of the production rate from studies of 10-12 wk duration can be considered valid if reduced by 8-9%.