Cholecystectomy prevents expansion of the bile acid pool and inhibition of cholesterol 7α-hydroxylase in rabbits fed cholesterol

To study the effect of cholecystectomy on the regu- lation of classic and alternative bile acid syntheses, gallbladder- intact (n � 20) and cholecystectomized (n � 20) New Zealand White rabbits were fed either chow or chow with 2% choles- terol (3 g/day). After 10 days, bile fistulas were constructed in half of each rabbit group to recover and measure the bile acid pool and biliary bile acid flux. After cholesterol feeding, the bile acid pool size increased from 268 � 55 to 444 � 77 mg ( P � 0.01) with a 2-fold rise in the biliary bile acid flux in intact rabbits but did not expand the bile acid pool (270 � 77 vs. 276 � 62 mg), nor did the biliary bile acid flux increase in cholecystectomized rabbits. Ileal apical sodium-dependent bile acid transporter protein increased 46% from 93 � 6 to 136 � 23 units/mg ( P � 0.01) in the intact rabbits but did not change in cholecystectomized rabbits (104 � 14 vs. 99 � 19 units/mg) after cholesterol feeding. Cholesterol 7 � -hydroxylase activity was inhibited 59% ( P � 0.001) while cholesterol 27-hydroxylase activity rose 83% ( P � 0.05) after cholesterol feeding in the in- tact rabbits but neither enzyme activity changed significantly in cholesterol-fed cholecystectomized rabbits. Fecal bile acid out- puts reflecting bile acid synthesis increased significantly in the intact but not in the cholecystectomized rabbits fed choles- terol. Removal of the gallbladder prevented expansion of the bile acid pool after cholesterol feeding as seen in intact rabbits because ileal bile acid transport did not increase. As a result, cholesterol 7 � -hydroxylase was not inhibited. —Xu, G., G. Salen, B. L. Shneider, M. Ananthanarayanan, S. Shefer, L. Ma, A. Batta, L. B. Nguyen, J. J. Lingutla, G. S. Tint, M. Pcolinsky, and F. J. Suchy. Cholecystectomy prevents expansion of the bile acid pool and inhibition of cholesterol 7 � -hydroxylase in rab- bits fed cholesterol. J. Lipid Res. 2001. 42: 1438-1443.