Abstract
The effects were studied of dietary lipid, dietary cholesterol and abministered insulin on 3-hy- droxy-3-methylglutaryl Co. A. reductase activity and serum cholesterol level in normal and alloxan diabetic rat liver.
The normal rats had been maintained on 0%, 5%, 10% or 20% fat-diet for 5 days. The amount of diet fed was adjusted so that each animal was given 60 calories daily. The enzyme activity was stimulated even with the feeding of a 5% fat-diet. The highest activities were obtained with the 10% and 20% fat-diets. The content of fat in the diet apparently regulate the level of the reductase activity, and 10% fat in the diet seems to be enough to achieve the maximum response of this enzyme.
The administration of insulin caused marked and rapid response of HMG-CoA reductase in normal and diabetic rats fed 0% or 10% fat-diet. However the stimulated activities of reductase were higher in animals maintained on 10% fat-diet than in those on 0%. The effects of dietary lipid and insulin administration on the reductase activity were shown to be additive.
On the other hand, the stimulatory effect of dietary lipid on reductase was completely blocked when cholesterol was added to the diet. This result suggests that cholestrol exerts its effect on the reductase activity at the more basic point of regulatory mechanism.
While producing widely different reductase activities, a number of dietary and hormonal manipulations produced no change in the level of serum cholesterol except in a group of diabetics on cholesterol diet. Despite its low activity of the reductase, the serum cholesterol level was slightly increased. This result strongly suggests that hepatic cholesterogenesis is not the sole determinant of serum cholesterol level and that other factor (s) such as catabolism of cholesterol may influence it.
