Feedback regulation of cholesterol biosynthesis in rhesus monkeys with variable hypercholesterolemic response to...

To test the hypothesis that high-responding rhesus monkeys should have a greater degree of feedback inhibition of hepatic cholesterol biosynthesis than the low-responding monkeys because the former group absorbs a higher percentage of cholesterol than the later group, we determined the relative rates of cholesterol biosynthesis by measuring plasma desmosterol levels while feeding triparanol along with diets high and low in cholesterol and with or without 2% plant sterols. The build-up of plasma desmosterol was more rapid in low-responders than in high-responders on all diets; the difference was significant only on diets low in plant sterols. In both groups, adding plant sterols to either diet increased the initial slope of plasma desmosterol build-up (significant only for high cholesterol diet). The mean percent cholesterol absorption in high-responders was significantly higher than in low-responders on high and low cholesterol diets with low levels of plant sterols. On adding 2% plant sterols to both diets, the percent cholesterol absorption decreased significantly and became essentially the same in both groups. Triparanol feeding decreased plasma cholesterol significantly in both groups on both diets; the decrease in the low-responders was smaller than in high-responders. Addition of plant sterols to either diet also reduced plasma cholesterol in both groups, but the decrease was significant only in the high-responders on high cholesterol diet. The study demonstrates that high-responders have a greater degree of feedback inhibition of cholesterol biosynthesis than low-responders probably because of higher absorption of cholesterol. The results also indicate that both endogenous and exogenous cholesterol are effective mediators of the feedback inhibition mechanism.