Cholesterol Metabolism in Human Gallbladder Mucosa: Relationship to Cholesterol Gallstone Disease and Effects of Chenodeoxycholic Acid and Ursodeoxycholic Acid Treatment

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Abstract
The objective of this study was to investigate cholesterol metabolism in human gallbladder mucosa, especially in relation to hepatic cholesterol metabolism, gallstone disease and treatment with bile acids. Gallbladder mucosa and liver tissue samples were collected in 44 patients undergoing cholecystectomy; 30 had cholesterol gallstones and the rest were stone free. Ten of the gallstone patients were treated with chenodeoxycholic acid and eight received ursodeoxycholic acid, with a daily dose of 15 mg/kg body wt, for 3 wk before surgery. The 3–hydroxy–3–methylglutaryl coenzyme A reductase activity, governing cholesterol synthesis, was considerably lower in the gallbladder mucosa than in liver tissue (28 ± 6 and 120 ± 40 pmol/min/mg protein). The acyl coenzyme A:acyltransferase activity in the gallbladder mucosa catalyzing the esterification of cholesterol was, on the other hand, several times higher than corresponding activity in the liver (92 ± 23 and 11 ± 2 pmol/min/mg protein). In the presence of exogenous cholesterol, the acyl coenzyme A:acyltransferase activity increased about twofold in the gallbladder mucosa. The acyl coenzyme A:acyltransferase activity of the gallbladder mucosa from untreated gallstone patients was not stimulated further by the addition of exogenous cholesterol. Otherwise, there were no significant differences in acyl coenzyme A:acyltransferase and 3–hydroxy–3–methylglutaryl coenzyme A reductase activities in the gallbladder mucosa of gallstone patients compared with gallstone–free controls. Treatment with chenodeoxycholic and ursodeoxycholic acids did not affect the 3–hydroxy–3–methylglutaryl coenzyme A reductase activity of the gallbladder mucosa but reduced the acyl coenzyme A:acyltransferase activity by 60% to 65%. A positive correlation was obtained between the cholesterol concentration in bile and the acyl coenzyme A:acyltransferase activity in the gallbladder mucosa in the whole series of patients (Spearman's rank–order correlation coefficient [rS] = 0.42, p < 0.05). We conclude that human gallbladder mucosa has a lower 3–hydroxy–3–methylglutaryl coenzyme A reductase activity but acyl coenzyme A:acyltransferase activity several times higher than that in liver tissue. Disturbance of cholesterol metabolism in the gallbladder mucosa, which might contribute to the high cholesterol content of gallbladder bile in patients with cholesterol gallstones, was not found. (Hepatology 1992;16:320-326.)

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