Studies on the mechanism of action of unsaturated fats on cholesterol metabolism in the rabbit.

The original observation by Kinsell and his associates (3) and by Groen and his associates (4) that the feeding of saturated fats results in an elevation whereas the feeding of unsaturated fats causes a lowering of serum cholesterol has been confirmed repeatedly in both man (5-7) and experimental animals (7-10). Theoretically, unsaturated fats might produce a lowering of serum cholesterol in at least four ways: by increasing the excretion or degradation of cholesterol, by inhibiting cholesterol synthesis, by interfering with the absorption of cholesterol, or by effecting a redistribution of cholesterol between serum and tissues either directly or via an influence on lipoprotein metabolism. Previous attempts to elucidate the mechanism or mechanisms responsible for this action have not demonstrated any consistently reproducible effects either on cholesterol excretion or degradation (11-15) or on cholesterol synthesis (16-20), and consequently it has been suggested by exclusion that unsaturated fats cause a redistribution of cholesterol between serum and the tissues (15). However, attempts to demonstrate directly that a shift of cholesterol occurs under circumstances of isocaloric fat substitution have not been successful (19). Two recent observations made it logical to reevaluate the possible mechanisms of this cholesterol-lowering effect. First, Wigand has clearly