Production of plasma esterified cholesterol in lean, normotriglyceridemic humans

The rate of production of plasma esterified cholesterol was measured both in vivo and in vitro in seven subjects and in vivo alone in eight subjects. All subjects were lean, clinically healthy, and had triglyceride concentrations less than 1.5 micro moles/ml. In vivo production was calculated from the labeling of free and esterified cholesterol in plasma samples collected at 1-hr intervals for 8 hr after an intravenous injection of [(3)H]mevalonic acid, on the assumption that plasma free cholesterol was the sole immediate precursor of esterified cholesterol. In vitro production was measured in serum samples collected 1 hr after the injection of [(3)H]mevalonic acid (when radioactivity in esterified cholesterol was very low relative to that in free cholesterol); these samples were incubated for 1 hr at 37 degrees C. The rates measured in vivo and in vitro were very similar in the seven subjects, strengthening the confidence in the techniques. In vivo production was measured during the postabsorptive state in all 15 subjects and in 5 of them also during the last 8 hr of a 32-56-hr period when all calories were taken in three hourly meals of an 80% carbohydrate, fat-free formula. In the postabsorptive state there was no apparent relationship between the production of esterified cholesterol and the concentration of either free or esterified cholesterol. Rather, despite a wide range of cholesterol concentrations, esterified cholesterol production was similar in all subjects. During the carbohydrate consumption the esterified cholesterol concentrations were significantly lower than during the postabsorptive state, but there was virtually no change in rate of production. It has been concluded that the differences in concentration of esterified cholesterol in lean, normotriglyceridemic subjects cannot be explained solely on the basis of differences in its production.