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Effects of treatment with deoxycholic acid and chenodeoxycholic acid on the hepatic synthesis of cholesterol and bile acids in healthy subjects
Author(s) -
Einarsson Curt,
Hillebrant CarlGustaf,
Axelson Magnus
Publication year - 2001
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1053/jhep.2001.23790
Subject(s) - chenodeoxycholic acid , deoxycholic acid , bile acid , medicine , cholesterol , reductase , chemistry , lithocholic acid , endocrinology , enzyme , biochemistry
The degradation of cholesterol to bile acids is regulated by a negative‐feedback mechanism by the bile acids, especially the hydrophobic bile acids, returning to the liver via the portal vein. Chenodeoxycholic acid (CDCA) is a potent suppressor of the cholesterol 7α‐hydroxylase, the rate‐determining enzyme in bile acid formation. CDCA may also suppress hepatic 3‐hydroxy‐3‐methyl glutaryl coenzyme A (HMG CoA) reductase, the rate‐limiting enzyme in cholesterol synthesis. Conflicting reports have appeared regarding the suppression on bile acid synthesis by the most hydrophobic bile acid of human bile, deoxycholic acid (DCA). To study the suppressive effects of CDCA and DCA on hepatic cholesterol and bile acid synthesis in humans, 10 healthy subjects were treated with CDCA or DCA for 3 weeks in a randomized cross‐over study with a washout period of 4 weeks in between. Serum levels of 7α‐hydroxy‐4‐cholesten‐3‐one, reflecting cholesterol 7α‐hydroxylase activity, and 7‐dehydrocholesterol, reflecting HMG CoA reductase activity, and bile acids were repeatedly measured during the study periods. After 3 weeks of treatment with CDCA or DCA, CDCA constituted 70% and DCA 74% of the total serum bile acids, respectively. CDCA and DCA decreased the serum levels of 7α‐hydroxy‐4‐cholesten‐3‐one by 80% and 75%, respectively. Negative correlations between the percentages of CDCA and DCA and the serum concentration of 7α‐hydroxy‐4‐cholesten‐3‐one were obtained. CDCA reduced the serum level of 7‐dehydrocholesterol by 29%, whereas treatment with DCA tended to increase the level of 7‐dehydrocholesterol. Treatment of healthy subjects with CDCA and DCA reduces bile acid synthesis. CDCA also inhibits cholesterol synthesis, whereas DCA does not.