Enhanced synthesis of cholesterol and its precursors in jejunal mucosa in coeliac disease

Abstract

Patients with coeliac disease have a greatly enhanced whole body synthesis of cholesterol, but its origin is not known. In this paper the synthesis and concentrations of cholesterol and its precursors, squalene and methyl sterols, were studied in jejunal biopsies from healthy volunteers and adult patients with coeliac disease. The incorporation rates of 14C-acetate and 3H-mevalonate into non-saponifiable lipids (sum of squalene, methyl sterols and cholesterol) were increased 14 and six times in the damaged mucosa, respectively. The cyclisation rate of mucosal squalene and the conversion of squalene to cholesterol were also increased, indicating that cholesterol synthesis was activated before mevalonate, probably at the step of HMG-CoA reductase, and also after mevalonate and squalene. The steps from squalene to cholesterol were apparently not rate limiting because the mucosal concentrations and the percentage distribution of squalene and sterols were similar in the patients and in the controls. A positive correlation of the cholesterol synthesis with the number of crypt cells, suggests that the expanded crypt cell population contributed to the enhanced intestinal cholesterologenesis. Furthermore, the serum cholesterol level was negatively correlated with the 14C- and 3H-counts in the mucosal cholesterol and with the cyclisation rate of squalene probable signs of regulatory role of serum low density lipoprotein cholesterol in intestinal cholesterol synthesis. Consequently, provided that the synthesis of mucosal cholesterol is as high in vivo as in vitro it could contribute to the highly increased overall synthesis of cholesterol in the patients with coeliac disease.