Journal of Lipid Research, Vol. 19, 972-977, November 1978
Copyright © 1978 by Lipid Research, Inc.

Influence of cholestyramine on synthesis of cholesterol and bile acids in germfree rats

Bengt E. Gustafsson , Bo Angelin , Kurt Einarsson , and Jan-Åke Gustafsson

Department of Germfree Research and Department of Chemistry, Karolinska Institutet, 104 01 Stockholm 60, and Department of Medicine, Serafimerlasarettet, 112 83 Stockholm, Sweden

The present investigation describes the influence of partial, pharmacologic interruption of bile acid enterohepatic circulation on cholesterol and bile acid synthesis in germfree rats. Seven rats received a basal, semisynthetic diet and five rats received the basal diet supplemented with 5% cholestyramine. After 6 weeks, feces were collected in one 3- and one 4-day pool for analysis of bile acids and cholesterol. When the sampling period was concluded, the rats were killed and the liver microsomal fractions were isolated. The activities of HMG CoA reductase and 7-hydroxylase were determined. The main fecal bile acids in the untreated rats were cholic acid and ßbeta;-muricholic acid. During cholestyramine treatment cholic acid increased from 4.4 ± 0.7 to 39.5 ± 5.6 mg/kg body weight/day and ßbeta;-muricholic acid from 4.5 ± 0.6 to 7.7 ± 0.9 mg/kg body weight/day. Chenodeoxycholic acid became a major bile acid averaging 10.4 ± 1.6 mg/kg body weight/day. The total amount of bile acids increased about 6-7 times and the percentage of cholic acid increased from 49.4 ± 2.0 to 68.6 ± 1.1%. The 7-hydroxylase activity increased 4-5 times. During cholestyramine treatment the fecal excretion of cholesterol was increased from 12.0 ± 1.4 to 68.0 ± 5.0 mg/kg body weight/day. The endogenous formation of cholesterol was increased 6 times and the HMG CoA reductase activity was increased about 20 times. In conclusion, germfree rats, like conventional rats, have the ability to increase the endogenous formation of bile acids and cholesterol during interruption of the enterohepatic circulation of bile acids, which is also reflected in a stimulation of the activities of the rate-determining enzymes.

Supplementary key words HMG CoA reductase • 7-hydroxylase • cholic acid • chenodeoxycholic acid • ßbeta;-muricholic acid

Submitted on December 19, 1977
Accepted on April 25, 1978

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