Hepatic metabolism of cholesterol in Crohn's disease. Effect of partial resection of ileum

Gastroenterology. 1991 Apr;100(4):1046-53. doi: 10.1016/0016-5085(91)90281-o.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Bile Acids and Salts / chemistry
  • Cholesterol / biosynthesis
  • Cholesterol / blood
  • Cholesterol / metabolism*
  • Cholesterol 7-alpha-Hydroxylase / metabolism
  • Cholesterol, LDL / blood
  • Coenzyme A / metabolism
  • Colectomy
  • Crohn Disease / enzymology
  • Crohn Disease / metabolism*
  • Crohn Disease / surgery
  • Female
  • Humans
  • Ileum / surgery*
  • Liver / enzymology
  • Male
  • Middle Aged
  • Receptors, LDL / metabolism


  • Bile Acids and Salts
  • Cholesterol, LDL
  • Receptors, LDL
  • Cholesterol
  • Cholesterol 7-alpha-Hydroxylase
  • Coenzyme A