Hepatic cholesterol metabolism in patients with cholesterol gallstones: Enhanced intracellular transport of cholesterol

Abstract

Background and Aims: Alterations of hepatic cholesterol metabolism in patients with cholesterol gallstones are still controversial. This study investigated whether hepatic cholesterol metabolism is altered in Japanese patients with cholesterol gallstones. Methods: In this systematic study of 24 middle-aged nonobese and nondiabetic Japanese patients who had cholesterol gallstones and were undergoing elective cholecystectomy, an analysis of three regulatory enzymes in the cholesterol metabolism, as well as cytosolic total and free cholesterol levels and sterol carrier protein 2/nonspecific lipid transfer protein (SCP2/nsLTP) levels, was conducted using liver biopsy samples obtained during surgery. Results: The activities of 3-hydroxy-3- methylglutaryl-coenzyme A (HMG-CoA) reductase, cholesterol 7α-hydroxylase, and acyl-CoA/cholesterol acyltransferase were not significantly different between patients and controls. Nevertheless, patients with gallstones showed tendencies for elevated HMG-CoA reductase activity and protein content and decreased cholesterol 7α-hydroxylase activities. As anticipated, serum levels of 7α-hydroxycholesterol and squalene paralleled these findings. The patients with gallstones also had significantly increased cytosolic total and free cholesterol levels (P < 0.001), which correlated strongly with increased cytosolic levels of SCP2/nsLTP (r = 0.80, P < 0.001 and r = 0.81, P < 0.001, respectively). Conclusions: The results suggest that intracellular cholesterol transport is enhanced in patients with cholesterol gallstones.