CHOLESTEROL AND BILE-ACID METABOLISM AFTER SELECTIVE PORTAL-VEIN LIGATION

Aim: To examine the regulatory effect of bile acid level on bile acid synthesis in the liver. Methods: The portal branch perfusing left late ral and median lobes of the liver was ligated in rats and the activiti es of hepatic microsomal cholesterol 7 alpha-hydroxylase, the rate-lim iting enzyme of bile acid synthesis, 3-hydroxy-3-methylglutaryl coenzy me A (HMG-CoA) reductase, and intrahepatic concentrations of cholester ol and bile acids were determined in the liver lobes deprived of and s upplied with portal blood on Days 0, 1, 2, 4, and 7 after selective po rtal vein ligation (SPVL). Results: In the portal vein (PV)-ligated lo bes, liver weight decreased, hepatic cholesterol concentration was unc hanged, and microsomal cholesterol concentration increased after SPVL. In the PV-nonligated lobes, liver weight increased, hepatic cholester ol concentration increased, and microsomal cholesterol concentration w as unchanged. There were no significant differences in the activities of HMG-CoA reductase and cholesterol 7 alpha-hydroxylase among the PV- ligated and PV-nonligated lobes and the sham-operated controls. Intrah epatic bile acid level increased significantly in the PV-nonligated lo bes for 4 days after SPVL, whereas those were essentially constant in the PV-ligated and the sham-operated control liver. Despite significan t changes in the concentrations of intrahepatic cholesterol and bile a cid, no significant correlations were observed between these concentra tions and the activities of cholesterol 7 alpha-hydroxylase. Conclusio ns: SPVL causes atrophy and hypertrophy of the PV-ligated and nonligat ed liver lobes, respectively, without any significant changes in chole sterol and bile acid synthesis. Intrahepatic concentrations of bile ac ids and cholesterol have no regulatory effect on cholesterol 7 alpha-h ydroxylase activity in the SPVL rat model. (C) 1997 Academic Press.