Kinetic analysis of cholesterol turnover in rat tissues

A number of studies have been conducted on serum cholesterol disappearance following a single injection of tracer. They have shown 2 or 3 component curves depending on the length of time of observation. They have been interpreted to indicate pools of cholesterol in fast or slow equilibrium with serum and generally depicted as representing groups of tissues. A cholesterol kinetic study was conducted using rats so that each tissue could be analyzed for appearance-disappearance of cholesterol from 30 minutes to 75 days. Serum and liver appeared to die-away for 30 days in a 2 component configuration, then exhibited a repetition of the same curve in the next 30 days. Skeletal muscle and kidney had a slow buildup for 2 weeks, then a plateau for 2 weeks then a 2 component die-away. Adipose showed a high plateau from 30 minutes to 30 days then a 2 component die-away, with specific activity higher than serum at all times. The data are interpreted to indicate that adipose tissue sequestered part of the tracer dose and all tissues reached equilibrium at about 30 days. After that time all tissues had a statistically significant 2 component die-away curve. The mathematical models tested suggest that in the steady state, cholesterol enters and exits the slow pool of serum, kidney, muscle and adipose and in liver enters both pools. Interpretation of the complete die-away is that the tracer dose first equilibrates with membrane free cholesterol, then with the intracellular cholesterol, and finally dies-away at the rate of release by the slow intercellular pool.