Regulation of sterol synthesis in human intestinal mucosa

The effect of dietary factors and experimental manipulations designed to perturb the enterohepatic circulation on the rate of sterol synthesis were studied in freshly isolated human jejunal mucosa from normal subjects. Fasting significantly reduced the rate of sterol synthesis from [14C]acetate in jejunal mucosa obtained from normolipaemic obese subjects. A high cholesterol diet had no consistent effect on the synthesis in normal subjects. Administration of cholestyramine resulted in a marked rise in the incorporation of [14C]acetate into sterols, while the administration of chenodeoxycholic acid did not significantly reduce basal sterol synthesis in normal subjects. These results demonstrate that in man the rate of sterol synthesis in intestinal mucosa is altered in response to physiological variables. Although these findings indicate that sterol synthesis in this tissue is subject to regulation, no difference was observed in basal sterol synthesis between normal subjects and patients heterozygous for familial hypercholesterolaemia.