Normal cholesterol absorption in rats deficient in intestinal acyl coenzyme A:cholesterol acyltransferase activity.
Acyl coenzyme A:cholesterol acyl transferase and/or cholesterol esterase may regulate the esterification and absorption of exogenous cholesterol. To assess this, mucosal acyl coenzyme A:cholesterol acyl transferase activity was inhibited selectively with three different drugs [Sandoz #58-035, inhibitor 1; Lederle inhibitor 2 and inhibitor 3] and the effect upon the absorption of a [4-14C]cholesterol meal was studied in the lymph fistula rat. Compared to control rats, ACAT activity measured in mucosal homogenates from the drug-treated rats was reduced 80-90%, 40%, and 30%, respectively, during the predicted time-frame for maximum mucosal esterification of cholesterol (i.e., after cholesterol is fed and before it appears in lymph). In contrast, [14C]cholesterol absorption in the drug-treated animals was unchanged from controls [5.7 +/- 1.2 (inhibitor 1) vs. 5.4 +/- 1.6 mumol/6 hr (control); 6.1 +/- 2.1 (inhibitor 2) and 5.2 +/- 1.5 (inhibitor 3) vs. 4.1 +/- 1.3 mumol/6 hr (control)]. Of the absorbed [14C]cholesterol, approximately 75% was esterified in all groups. Cholesterol esterase activity measured in the drug-treated rats was unchanged compared to controls nor did the drugs inhibit this enzyme in vitro. Under the conditions of this study, drugs causing substantial inhibition of acyl coenzyme A:cholesterol acyl transferase activity had no effect on the absorption of exogenous cholesterol.
D000818:Animals; D002784:Cholesterol / Q000378:metabolism*; D002788:Cholesterol Esters / Q000378:metabolism; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000378:metabolism; D008196:Lymph / Q000378:metabolism; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D002787:Sterol Esterase / Q000378:metabolism; D002785:Sterol O-Acyltransferase / Q000037:antagonists & inhibitors / Q000172:deficiency*
D002788:Cholesterol Esters; D002784:Cholesterol; D002785:Sterol O-Acyltransferase; D002787:Sterol Esterase