HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 285/3/G494    most recent 00156.2003v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (19) Citing Articles via Google Scholar Google Scholar Articles by Wang, D. Q.-H. Articles by Carey, M. C. Search for Related Content PubMed PubMed Citation Articles by Wang, D. Q.-H. Articles by Carey, M. C.

LIVER AND BILIARY TRACT

Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption: studies in the gallstone-susceptible mouse

¹Division of Gastroenterology, Department of Medicine, Beth Israel Deaconess Medical Center, and ²Division of Gastroenterology, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School and Harvard Digestive Diseases Center, Boston, Massachusetts 02215; ³First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima 734-8551, Japan; and ⁴Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, New York 10461

Submitted 2 April 2003 ; accepted in final form 7 May 2003

We explored the influence of the hydrophilic-hydrophobic balance of a series of natural bile acids on cholesterol absorption in the mouse. Male C57L/J mice were fed standard chow or chow supplemented with 0.5% cholic; chenodeoxycholic; deoxycholic; dehydrocholic; hyocholic; hyodeoxycholic; -, -, or -muricholic; ursocholic; or ursodeoxycholic acids for 7 days. Biliary bile salts were measured by reverse-phase HPLC, and hydrophobicity indices were estimated by Heuman's method. Cholesterol absorption efficiency was determined by a plasma dual-isotope ratio method. In mice fed chow, natural proportions of tauro--muricholate (42 ± 6%) and taurocholate (50 ± 7%) with a hydrophobicity index of -0.35 ± 0.04 produced cholesterol absorption of 37 ± 5%. Because bacterial and especially hepatic biotransformations of specific bile acids occurred, hydrophobicity indices of the resultant bile salt pools differed from fed bile acids. We observed a significant positive correlation between hydrophobicity indices of the bile salt pool and percent cholesterol absorption. The principal mechanism whereby hydrophilic bile acids inhibit cholesterol absorption appears to be diminution of intraluminal micellar cholesterol solubilization. Gene expression of intestinal sterol efflux transporters Abcg5 and Abcg8 was upregulated by feeding cholic acid but not by hydrophilic -muricholic acid nor by hydrophobic deoxycholic acid. We conclude that the hydrophobicity of the bile salt pool predicts the effects of individual fed bile acids on intestinal cholesterol absorption. Natural - and -muricholic acids are the most powerful inhibitors of cholesterol absorption in mice and might act as potent cholesterol-lowering agents for prevention of cholesterol deposition diseases in humans.

ATP-binding cassette transporters; bile flow; bile salt pool size; biliary secretion; mixed micelles

This article has been cited by other articles:

				D. Jung, T. Inagaki, R. D. Gerard, P. A. Dawson, S. A. Kliewer, D. J. Mangelsdorf, and A. Moschetta FXR agonists and FGF15 reduce fecal bile acid excretion in a mouse model of bile acid malabsorption J. Lipid Res., December 1, 2007; 48(12): 2693 - 2700. [Abstract] [Full Text] [PDF]

				E. Sehayek, L. R. Hagey, Y.-Y. Fung, E. M. Duncan, H. J. Yu, G. Eggertsen, I. Bjorkhem, A. F. Hofmann, and J. L. Breslow Two loci on chromosome 9 control bile acid composition: evidence that a strong candidate gene, Cyp8b1, is not the culprit J. Lipid Res., September 1, 2006; 47(9): 2020 - 2027. [Abstract] [Full Text] [PDF]

				J. Wang, C. Einarsson, C. Murphy, P. Parini, I. Bjorkhem, M. Gafvels, and G. Eggertsen Studies on LXR- and FXR-mediated effects on cholesterol homeostasis in normal and cholic acid-depleted mice J. Lipid Res., February 1, 2006; 47(2): 421 - 430. [Abstract] [Full Text] [PDF]

				L.-P. Duan, H. H. Wang, A. Ohashi, and D. Q.-H. Wang Role of intestinal sterol transporters Abcg5, Abcg8, and Npc1l1 in cholesterol absorption in mice: gender and age effects Am J Physiol Gastrointest Liver Physiol, February 1, 2006; 290(2): G269 - G276. [Abstract] [Full Text] [PDF]

				J. J. Repa, S. D. Turley, G. Quan, and J. M. Dietschy Delineation of molecular changes in intrahepatic cholesterol metabolism resulting from diminished cholesterol absorption J. Lipid Res., April 1, 2005; 46(4): 779 - 789. [Abstract] [Full Text] [PDF]

				H. H. Wang, N. H. Afdhal, S. J. Gendler, and D. Q.-H. Wang Lack of the intestinal Muc1 mucin impairs cholesterol uptake and absorption but not fatty acid uptake in Muc1-/- mice Am J Physiol Gastrointest Liver Physiol, September 1, 2004; 287(3): G547 - G554. [Abstract] [Full Text] [PDF]