Dietary cholesterol-induced down-regulation of intestinal 3-hydroxy-3-methylglutaryl coenzyme A reductase activity is diminished in rabbits with hyperresponse of serum cholesterol to dietary cholesterol.

Key enzymes of cholesterol metabolism were studied in two inbred strains of rabbits with hyper- or hyporesponse of serum cholesterol to dietary cholesterol. Baseline 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity in liver was similar in hypo- and hyperresponders, but that in intestine was twofold higher in the hyporesponders. The addition of cholesterol (3 g/kg) to the diet caused similar depression of hepatic HMG-CoA reductase activity in the two strains, whereas intestinal HMG-CoA reductase activity was significantly reduced in hyporesponders but not in hyperresponders. Cholesterol feeding induced higher free cholesterol concentrations in hepatic and intestinal microsomes of both hypo- and hyperresponders and higher activity of hepatic acyl-CoA:cholesterol acyltransferase (ACAT). Hepatic ACAT activity was significantly lower in cholesterol-fed hyperresponders than in hyporesponders, which may have contributed to the observed higher free cholesterol concentrations in hepatic microsomes of cholesterol-fed hyperresponders. Intestinal ACAT activity was similar in hypo- and hyperresponders; cholesterol feeding tended (P = 0.11) to elevate the activity of this enzyme. Hepatic cholesterol 7 alpha-hydroxylase activity was significantly higher in cholesterol-fed hyperresponders than in hyporesponders; it was slightly depressed after cholesterol loading in both rabbit strains.