EXOGENOUS HYPERCHOLESTEROLEMIC RATS, COMPARED WITH THEIR PROGENITOR, SPRAGUE-DAWLEY RATS, PROMPTLY ALTER CHOLESTEROL-METABOLISM IN THE LIVER AND SECRETE CHOLESTEROL-RICH PARTICLES IN RESPONSE TO DIETARY-CHOLESTEROL

Early responses of cholesterol metabolism to dietary cholesterol were compared between exogenous hypercholesterolemic (ExHC) and Sprague-Daw ley rats. Both strains had a similar radioactivity of [C-14]cholestero l in the serum half a day after the oral administration, but thereafte r the radioactivity disappeared slowly in ExHC rats. ExHC rats promptl y altered in response to the dietary cholesterol, activities of choles terol 7 alpha-hydroxylase and cholesterol synthesis in the liver and f ecal excretion of bile acids derived from [C-14]cholesterol administer ed orally. Lymphatic transport for 24 hr of [C-14]cholesterol was simi lar between the strains. Triton administration resulted in a marked ac cumulation of cholesterol in serum d > 1.006 g/ml lipoproteins in ExHC rats; in addition, the formation of cholesteryl esters from [C-14]ole ic acid intravenously infused was greater in ExHC rats. These results indicate that ExHC rats increase serum cholesterol in response to exog enous cholesterol by decreasing the liver uptake and enhancing the sec retion in the liver.