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Am J Physiol Gastrointest Liver Physiol (May 14, 2003). doi:10.1152/ajpgi.00156.2003
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Submitted on April 2, 2003
Accepted on May 7, 2003

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

David Q. -H. Wang1*, Susumu Tazuma2, David E. Cohen3, and Martin C. Carey4

1 Department of Medicine, Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, MA, USA; Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School and Harvard Digestive Diseases Center, Boston, MA, USA
2 First Department of Internal Medicine, Hiroshima University School of Medicine, Hiroshima, Japan
3 Marion Bessin Liver Research Center, Albert Einstein College of Medicine, Bronx, NY, USA
4 Department of Medicine, Division of Gastroenterology, Brigham and Women's Hospital, Harvard Medical School and Harvard Digestive Diseases Center, Boston, MA, USA

* To whom correspondence should be addressed. E-mail: dqwang{at}caregroup.harvard.edu.

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 chow, or chow supplemented with 0.5% cholic, chenodeoxycholic, deoxycholic, dehydrocholic, hyocholic, hyodeoxycholic, {alpha}-, {beta}-, {omega}-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-{beta}-muricholate (42±6%) and taurocholate (50±7%) with a hydrophobicity index of -0.35±0.04 produced a 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 the 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 via diminution of intraluminal micellar cholesterol solubilization. Gene expression of the intestinal sterol efflux transporters Abcg5 and Abcg8 was up-regulated by feeding cholic acid, but not by the hydrophilic {beta}-muricholic acid nor by the 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 {alpha}- and {beta}-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.




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