title: Hepatic metabolism of cholesterol in Crohn's disease. Effect of partial resection of ileum.
abstract: To study cholesterol metabolism in Crohn's disease and especially the effect of ileum resection, liver biopsy specimens were obtained from patients undergoing partial ileal resection because of Crohn's disease (n = 17) and patients with Crohn's colitis undergoing colectomy (n = 3). Gallstone-free patients (n = 16) undergoing cholecystectomy because of adenomyomas or polyps of the gallbladder served as controls. The mean levels of cholesterol 7 alpha-hydroxylase activity and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, rate-determining enzymes in bile acid, and cholesterol synthesis, respectively, were twofold to threefold higher in the ileum-resected patients than in the controls. Significant positive correlations were obtained between length of resected ileum and cholesterol 7 alpha-hydroxylase activity. Provided patients who had received total parenteral nutrition preoperatively were excluded from analysis, a significant correlation was also observed between length of resected ileum and 3-hydroxy-3-methylglutaryl coenzyme A reductase activity. Significant positive correlations were also obtained between length of resected ileum and serum levels of 7 alpha-hydroxycholesterol (a marker for bile acid biosynthesis) and lathosterol (a marker for cholesterol synthesis). The plasma levels of total and low-density lipoprotein cholesterol were negatively correlated to the length of resected ileum. The expression of hepatic low-density lipoprotein-receptor binding activity was determined in five of the patients and in three of the controls. A significant positive correlation was observed between 3-hydroxy-3-methylglutaryl coenzyme A reductase activity and low-density lipoprotein-receptor binding activity. The results show that malabsorption of bile acids leads to parallel stimulation of cholesterol synthesis, cholesterol degradation, and low-density lipoprotein-receptor expression in human liver. The resulting effect in the present patients was a significant reduction in low-density lipoprotein cholesterol.
authors.affiliation: Department of Surgery, Karolinska Institute, Huddinge University Hospital, Sweden.
authors.forename: J E
authors.initials: JE
authors.lastname: Akerlund
authors.forename: E
authors.initials: E
authors.lastname: Reihnér
authors.forename: B
authors.initials: B
authors.lastname: Angelin
authors.forename: M
authors.initials: M
authors.lastname: Rudling
authors.forename: S
authors.initials: S
authors.lastname: Ewerth
authors.forename: I
authors.initials: I
authors.lastname: Björkhem
authors.forename: K
authors.initials: K
authors.lastname: Einarsson
mesh_terms: D000328:Adult; D001647:Bile Acids and Salts / Q000737:chemistry; D002784:Cholesterol / Q000096:biosynthesis / Q000097:blood / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D008078:Cholesterol, LDL / Q000097:blood; D003065:Coenzyme A / Q000378:metabolism; D003082:Colectomy; D003424:Crohn Disease / Q000201:enzymology / Q000378:metabolism* / Q000601:surgery; D005260:Female; D006801:Humans; D007082:Ileum / Q000601:surgery*; D008099:Liver / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D008078:Cholesterol, LDL; D011973:Receptors, LDL; D002784:Cholesterol; D002790:Cholesterol 7-alpha-Hydroxylase; D003065:Coenzyme A