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

David Q.H. Wang, Susumu Tazuma, David E. Cohen, Martin C. Carey

Research output: Contribution to journalArticle

98 Citations (Scopus)

Abstract

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; α-, β-, or ω-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-β-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 β-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 α- and β-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.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume285
Issue number3 48-3
StatePublished - Sep 1 2003
Externally publishedYes

Fingerprint

Intestinal Absorption
Gallstones
Bile Acids and Salts
Cholesterol
Hydrophobic and Hydrophilic Interactions
Anticholesteremic Agents
Cholic Acid
Ursodeoxycholic Acid
Taurocholic Acid
Deoxycholic Acid
Sterols
Biotransformation
Isotopes
High Pressure Liquid Chromatography
Gene Expression
Liver

Keywords

  • ATP-binding cassette transporters
  • Bile flow
  • Bile salt pool size
  • Biliary secretion
  • Mixed micelles

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

Cite this

Feeding natural hydrophilic bile acids inhibits intestinal cholesterol absorption : Studies in the gallstone-susceptible mouse. / Wang, David Q.H.; Tazuma, Susumu; Cohen, David E.; Carey, Martin C.

In: American Journal of Physiology - Gastrointestinal and Liver Physiology, Vol. 285, No. 3 48-3, 01.09.2003.

Research output: Contribution to journalArticle

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