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

Guorong Xu,Gerald Salen,Benjamin L Shneider,M Ananthanarayanan,Sarah Shefer,Lin Ma,Ashok Batta,Lien B Nguyen,Josephine J Lingutla,G Stephen Tint,Mark Pcolinsky,Frederick J Suchy

doi:10.1016/s0022-2275(20)30276-5

Abstract

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 7α-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 7α-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 7α-hydroxylase in rabbits fed cholesterol.

Highlights

To study the effect of cholecystectomy on the regulation of classic and alternative bile acid syntheses, gallbladderintact (n ‫ ؍‬20) and cholecystectomized (n ‫ ؍‬20) New Zealand White rabbits were fed either chow or chow with 2% cholesterol (3 g/day)
When the cholecystectomized rabbits consumed the regular chow diet, plasma and hepatic cholesterol concentrations as well as cholesterol and bile acid biosyntheses were unchanged as evidenced by nearly equal activities for their respective rate-controlling enzymes, HMG-CoA reductase, cholesterol 7␣-hydroxylase, and cholesterol 27-hydroxylase compared with the baseline in the intact rabbits
The explanation for the failure to downregulate cholesterol 7␣-hydroxylase and classic bile acid synthesis after cholecystectomy seems related to the fact that the bile acid pool, which had expanded significantly after cholesterol feeding in rabbits with gallbladders, did not enlarge during cholesterol feeding in rabbits without gallbladders

Summary

Introduction

To study the effect of cholecystectomy on the regulation of classic and alternative bile acid syntheses, gallbladderintact (n ‫ ؍‬20) and cholecystectomized (n ‫ ؍‬20) New Zealand White rabbits were fed either chow or chow with 2% cholesterol (3 g/day). Ileal apical sodium-dependent bile acid transporter protein increased 46% from 93 ؎ 6 to 136 ؎ 23 units/mg (P Ͻ 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 Ͻ 0.001) while cholesterol 27-hydroxylase activity rose 83% (P Ͻ 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. Cholecystectomy prevents expansion of the bile acid pool and inhibition of cholesterol 7␣-hydroxylase in rabbits fed cholesterol.

Methods

Results

Conclusion