Regulation of bile acid synthesis in humans: Studies on cholesterol 7 α-hydroxylation in vivo

M. Bertolotti, N. Abate, P. Loria, M. Concari, M. E. Guicciardi, M. A. Dilengite, M. Bozzoli, F. Carubbi, N. Carulli

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Over the last few years important progress has been made on the quantitation of cholesterol 7α-hydroxylation, the rate-limiting step of bile acid synthesis. The use of a technique based on the determination of body water tritium enrichment after i.v. administration of [7α-3H] cholesterol has allowed in vivo investigation of this step in humans in different experimental conditions. The cholesterol 7α-hydroxylation rate was not affected by the administration of the hydrophilic bile acid ursodeoxycholic acid (UDCA) whereas it was significantly reduced by the more hydrophobic chenodeoxycholic acid (CDCA) and even more so by the strongly hydrophobic deoxycholic acid (DCA). The administration of cholestyramine induced a significant dose-related increase of 7α-hydroxylation along with a correspondent decrease in plasma cholesterol. The administration of simvastatin exerted no effect on cholesterol 7α-hydroxylation despite a marked decrease in serum cholesterol. Treatment with fibrates reduced plasma lipid levels and 7α-hydroxylation rates. Hydroxylation rates were unchanged in familial hypercholesterolaemia and increased in familial combined hyperlipidaemia. These data suggest that in humans bile acid synthesis can be affected by quantitative and qualitative alterations of the enterohepatic circulation of bile acids. Changes in cholesterol 7α-hydroxylation rates may be associated with alterations in plasma lipid levels, but such a relationship is ill-defined and seems to vary with the different experimental models.

Original languageEnglish (US)
Pages (from-to)446-449
Number of pages4
JournalItalian Journal of Gastroenterology
Volume27
Issue number8
StatePublished - Dec 1 1995

Keywords

  • Chenodeoxycholic acid
  • Cholestyramine
  • Deoxycholic acid
  • Hyperlipaemia
  • Simvastatin

ASJC Scopus subject areas

  • Gastroenterology

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    Bertolotti, M., Abate, N., Loria, P., Concari, M., Guicciardi, M. E., Dilengite, M. A., Bozzoli, M., Carubbi, F., & Carulli, N. (1995). Regulation of bile acid synthesis in humans: Studies on cholesterol 7 α-hydroxylation in vivo. Italian Journal of Gastroenterology, 27(8), 446-449.