| Title | Regulation of diurnal variation of cholesterol 7alpha-hydroxylase (CYP7A1) activity in healthy subjects. | | Author(s) | Kovář J, Leníček V, Zimolová M, Vítek L, Jirsa M, Piťha P | | Institution | Institute for Clinical and Experimental Medicine, Laboratory for Atherosclerosis Research, Prague, Czech Republic. jan.kovar@medicon.cz. | | Source | Physiol Res 2009 Jun 19. | | Abstract | Cholesterol 7alpha-hydroxylase (CYP7A1), the key regulatory enzyme of bile acid synthesis, displays a pronounced diurnal variation. To better understand the regulation of CYP7A1 activity, three day-long examinations were carried out in 12 healthy men. The concentrations of 7alpha-hydroxycholest-4-en-3-one (C4), a surrogate marker of CYP7A1 activity, bile acids (BA), insulin, glucose, nonesterified fatty acids, triglyceride, and cholesterol were measured in serum in 90-min intervals from 7 AM till 10 PM. To lower and to increase BA concentration during the study, the subjects received cholestyramine and chenodeoxycholic acid, respectively, in two examinations. No drug was used in the control examination. The concentration of C4 showed out pronounced diurnal variation with a peak around 1 PM in most of the subjects. The area under curve (AUC) of C4 concentration was five times higher and three times lower when subjects were treated with cholestyramine and CDCA, respectively. No relationship was found between AUC of C4 and AUC of BA concentration, however, AUC of C4 was positively correlated with that of insulin. Moreover, short-term treatment with cholestyramine resulted in ~10 % suppression of glycemia throughout the day. Our results suggest that insulin is involved in regulation of diurnal variation of CYP7A1 activity in humans. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19537927 |
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