Reduced cholesterol transmucosal transport in rats with inhibited mucosal acyl CoA:cholesterol acyltransferase and normal pancreatic function

Abstract

Absorption of cholesterol during inhibition of mucosal acyl CoA:cholesterol acyltransferase was studied in mesenteric lymph fistula rats with normal pancreatic function. The specific inhibitor used (Sandoz Compound 58-035; 3-(decyldimethylsilyl)-N-[2-(4-methylphenyl)-1-phenylethyl]prop anamide) greatly reduced cholesterol esterification in vitro and decreased lymphatic secretion of esterified cholesterol in vivo, but did not affect triglyceride metabolism by the gut in vitro or in vivo. During steady state lymphatic transport of cholesterol, unesterified cholesterol was increased and cholesteryl esters were decreased in whole lymph, lymph chylomicrons, and very low density lipoproteins. Incorporation of labeled cholesterol infused into the lumen into cholesteryl esters of lymph very low density lipoproteins was particularly suppressed. Labeled cholesterol incorporation into individual cholesteryl esters differed and was differentially affected when total cholesteryl ester synthesis was inhibited. The results support a major regulatory role for mucosal acyl CoA:cholesterol acyltransferase in cholesterol absorption and imply differences in the metabolism of endogenous and exogenous cholesterol by the intestinal mucosa.