Hepatic cholesterol metabolism in human obesity

作者：Dagny Ståhlberg, Mats J. Rudling, Bo Angelin, Ingemar Björkhem, Pontus K. A. Larsson Forsell, KLAS NILSELL, Kurt Einarsson · 发表于：Hepatology · 年份：1997 · DOI：10.1002/hep.510250623 · 被引用次数：99 · 研究领域：Cholesterol and Lipid Metabolism、Cancer, Lipids, and Metabolism、Drug Transport and Resistance Mechanisms

Hepatic cholesterol metabolism was studied in operative liver biopsies from 17 morbidly obese subjects and compared with that in samples from 15 nonobese controls. The aim was to understand the mechanisms causing the hypersecretion of cholesterol into bile. The content of cholesteryl esters was increased threefold in the liver of obese subjects compared with that of the controls (P < .0001). The activity and the messenger RNA (mRNA) level of 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase, the rate limiting enzyme for cholesterol synthesis, were higher in the obese subjects compared with the nonobese subjects (75% and 140%, respectively; P < .01). In the obese subjects, the activity and mRNA level of cholesterol 7alpha-hydroxylase, which regulates the catabolism of cholesterol to bile acids, were also increased by 140% (P < .05) and 180% (P = .06), respectively, as compared with the controls. There was a significant correlation between the activities and the mRNA levels of cholesterol 7alpha-hydroxylase among the obese subjects (r = +0.65, P < .01). The activities of acyl-coenzyme A:cholesterol acyltransferase (ACAT), which governs cholesteryl ester formation, in obese and nonobese patients were 12.5 +/- 1.7 and 8.1 +/- 1.2 pmol/min/mg protein, respectively (P < .05), and the low-density lipoprotein (LDL) receptor mRNA levels were 5.3 +/- 0.7 and 4.5 +/- 0.9 molecules of mRNA/microg of RNA, respectively. We conclude that the activities of three key enzymes in hepati...