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

B. E. Gustafsson, B. Angelin, K. Einarsson, J. A. Gustafsson

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

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 7α-hydroxylase were determined. The main fecal bile acids in the untreated rats were cholic acid and β-muricholic acid. During cholestyramine treatment cholic acid increased from 4.4 ± 0.7 to 39.5 ± 5.6 mg/kg body weight/day and β-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 7α-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.

Original languageEnglish (US)
Pages (from-to)972-977
Number of pages6
JournalJournal of lipid research
Volume19
Issue number8
StatePublished - 1978

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Cell Biology

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