Oxysterols in bile acid metabolism

Increasing body of evidence is available indicating that oxysterols are more much than intermediates of metabolic pathways. Oxysterols play a role in the regulation of cholesterol synthesis, transport and efflux. A scavenger effect of cholesterol 27-hydroxylase on elevated serum cholesterol levels is well demonstrated. Bile acid synthesis occurs through two main pathways, the classic and the alternative ones. Since plasma concentrations of 27-hydroxycholesterol were clearly shown to reflect its production rate the alternative pathway of bile acid synthesis can be easily explored. Conversely this was not true for 7 alpha-hydroxycholesterol and also the direct evaluation of the classic pathway by kinetic studies is more difficult since the rate of plasma appearance during continuous infusion of deuterated isotopomers may not exactly measure its production rate. Hepatic cholesterol 7alpha-hydroxylase activity is absent during fetal life in humans and upregulates after birth. Both the classic and alternative pathways become mature after the age of 4 years. It has been clearly demonstrated that in patients with liver disease the classic pathway is impaired while the alternative one is preserved. Conversely, in obese patients, preliminary data suggest an increase of the production rate of 27-hydroxycholesterol, a possible mechanism to counteract the increase of atherosclerotic risk. (C) 2011 Elsevier B.V. All rights reserved.