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Journal of Lipid Research, Vol. 42, 1438-1443, September 2001
Copyright © 2001 by Lipid Research, Inc.

Original Article

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

Correspondence to: Gerald Salen, at GI Lab (15A), VA Medical Center, 385 Tremont Avenue, East Orange, NJ 07018-1095., salenge{at}umdnj.edu (E-mail)

To study the effect of cholecystectomy on the regulation 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% cholesterol (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 intact rabbits but neither enzyme activity changed significantly in cholesterol-fed cholecystectomized rabbits. Fecal bile acid outputs reflecting bile acid synthesis increased significantly in the intact but not in the cholecystectomized rabbits fed cholesterol.

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 rabbits fed cholesterol. J. Lipid Res. 2001. 42: 1438;–1443.

Supplementary key words: apical sodium-dependent bile acid transporter, sodium/taurocholate cotransporting polypeptide, bile acid synthesis, cholesterol 27-hydroxylase, bile acid transport

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