Biliary cholesterol excretion: a novel mechanism that regulates dietary cholesterol absorption

• Published in: Proceedings of the National Academy of Sciences - PNAS 1998-08, Vol.95 (17), p.10194-10199
• Main Authors: Sehayek, E. (The Rockefeller University, New York, NY.), Ono, J.G, Shefer, S, Nguyen, L.B, Wang, N, Batta, A.K, Salen, G, Smith, J.D, Tall, A.R, Breslow, J.L
• Format: Article
• Language: English
• Subjects: ABSORCION DIGESTIVA; ABSORPTION DIGESTIVE; ACIDE BILIAIRE; ACIDOS BILIARES; ACTIVIDAD ENZIMATICA; ACTIVITE ENZYMATIQUE; ANIMAL TRANSGENIQUE; ANIMALES TRANSGENICOS; Animals; Arteriosclerosis - prevention & control; BILE; Bile - metabolism; BILE ACIDS; BILIS; Biological Sciences; CD36 Antigens - genetics; CD36 Antigens - metabolism; CHOLESTEROL; Cholesterol - metabolism; Cholesterol 7-alpha-Hydroxylase - metabolism; CHOLESTEROL 7ALPHA-MONOOXYGENASE; Cholesterol, Dietary - administration & dosage; Cholesterol, Dietary - pharmacokinetics; Cholesterols; COLESTEROL; DIGESTIVE ABSORPTION; ENZYMIC ACTIVITY; EXCRECION; EXCRETION; FAECES; FECES; Female; FOOD INTAKE; HDL lipoproteins; HECES; Humans; Hydroxymethylglutaryl CoA Reductases - metabolism; HYDROXYMETHYLGLUTARYL-COA REDUCTASE; INGESTION DE ALIMENTOS; INTESTINAL ABSORPTION; Intestinal Absorption - physiology; Intestinal Mucosa - metabolism; Lipids; Liver; Liver - metabolism; Male; Medical research; Membrane Proteins; MICE; Mice, Inbred C57BL; Mice, Inbred CBA; Mice, Transgenic; OXIDOREDUCTASES; OXIDORREDUCTASAS; OXYDOREDUCTASE; PRISE ALIMENTAIRE (HOMME); RATON; RECEPTORS; Receptors, Immunologic; Receptors, Lipoprotein; Receptors, Scavenger; Rodents; SCAVENGER RECEPTOR BI; Scavenger Receptors, Class B; SOURIS; TRANSGENIC ANIMALS
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.95.17.10194

The regulation of dietary cholesterol absorption was examined in C57BL/6 and transgenic mice with liver overexpression of the scavenger receptor BI (SR-BI Tg). In C57BL/6 animals, feeding 0.02 to 1% (wt/wt) dietary cholesterol resulted in a dose-dependent decrease in the percentage of dietary cholesterol absorbed. A plot of total daily mass of dietary cholesterol absorbed versus the percentage by weight of cholesterol in the diet yielded a curve suggesting a saturable process with a Km of 0.4% (wt/wt) and a Vmax of 0.65 mg cholesterol/g body weight per day. Dietary cholesterol suppressed hepatic 3-hydroxy-3-methylglutaryl CoA reductase activity, stimulated cholesterol 7 alpha-hydroxylase activity, and enhanced fecal excretion of bile acids, but none of these changes correlated with the percentage of dietary cholesterol absorption. Dietary cholesterol also caused an increase in biliary cholesterol concentration, and in this case the concentration of biliary cholesterol was strongly and inversely correlated with the percentage dietary cholesterol absorption (r = -0.63, P 0.0001). Biliary cholesterol concentration was also directly correlated with daily cholesterol intake, dietary cholesterol mass absorption, and liver cholesterol ester content. Transgene-induced overexpression of SR-BI resulted in a stimulation of excretion of cholesterol into the bile and suppressed percentage dietary cholesterol absorption. Furthermore, biliary cholesterol levels in SR-BI Tg mice were strongly and inversely correlated with the percentage of dietary cholesterol absorbed (r