Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Cholesterol Feeding Prevents Hepatic Accumulation of Bile Acids in Cholic Acid-Fed Farnesoid X Receptor (FXR)-Null Mice: FXR-Independent Suppression of Intestinal Bile Acid Absorption

Masaaki Miyata, Yoshiki Matsuda, Masahiro Nomoto, Yuki Takamatsu, Nozomi Sato, Mayumi Hamatsu, Paul A. Dawson, Frank J. Gonzalez and Yasushi Yamazoe
Drug Metabolism and Disposition February 2009, 37 (2) 338-344; DOI: https://doi.org/10.1124/dmd.108.022590
Masaaki Miyata
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yoshiki Matsuda
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Masahiro Nomoto
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yuki Takamatsu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Nozomi Sato
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mayumi Hamatsu
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul A. Dawson
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Frank J. Gonzalez
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Yasushi Yamazoe
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Cholic acid (CA) feeding of farnesoid X receptor (Fxr)-null mice results in markedly elevated hepatic bile acid levels and liver injury. In contrast, Fxr-null mice fed cholesterol plus CA (CA+Chol) do not exhibit liver injury, and hepatic bile acid levels and bile acid pool size are reduced 51 and 40%, respectively, compared with CA-treated Fxr-null mice. These decreases were not observed in wild-type mice. Despite a reduced bile acid pool size, hepatic Cyp7a1 mRNA expression was increased in Fxr-null mice fed the CA+Chol diet, and biliary bile acid output was not changed. Analysis of other potential protective mechanisms revealed significant decreases in portal blood bile acid concentrations and a reduced ileal bile acid absorption capacity, as estimated using an in situ loop method. Fecal bile acid excretion was also increased in Fxr-null mice fed the CA+Chol versus CA diet. The decreased ileal bile acid absorption correlated with decreased ileal apical sodium-dependent bile salt transporter (ASBT) protein expression in brush-border membranes. These results suggest a critical role for ileal bile acid absorption in regulation of hepatic bile acid levels in Fxr-null mice fed CA+Chol. Furthermore, experiments with Fxr-null mice suggest that cholesterol feeding can down-regulate ASBT expression through a pathway independent of FXR.

Footnotes

  • This study was supported by the Ministry of Education, Science and Culture, Japan [Grants 17390039, 17590114]; the Ministry of Health, Labor and Welfare, Japan [Grant H17-toxico-ippan-001]; and the National Institutes of Health [Grant DK-47987].

  • Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.

  • doi:10.1124/dmd.108.022590.

  • ABBREVIATIONS: Chol, cholesterol; FXR, farnesoid X receptor; ASBT, apical sodium-dependent bile salt transporter; OSTα, organic solute transporter α; FGF, fibroblast growth factor; CA, cholic acid; TCA, taurocholic acid; TCDCA, taurochenodeoxycholic acid; DCA, deoxycholic acid; TDCA, taurodeoxycholic acid; HPLC, high-performance liquid chromatography; ALT, alanine aminotransferase; ALP, alkaline phosphatase; BBM, brush-border membrane; PCR, polymerase chain reaction; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; LXR, liver X receptor; PXR, pregnane X receptor.

    • Received May 29, 2008.
    • Accepted November 3, 2008.
  • U.S. Government work not protected by U.S. copyright.
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 37 (2)
Drug Metabolism and Disposition
Vol. 37, Issue 2
1 Feb 2009
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Back Matter (PDF)
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Cholesterol Feeding Prevents Hepatic Accumulation of Bile Acids in Cholic Acid-Fed Farnesoid X Receptor (FXR)-Null Mice: FXR-Independent Suppression of Intestinal Bile Acid Absorption
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

Cholesterol Feeding Prevents Hepatic Accumulation of Bile Acids in Cholic Acid-Fed Farnesoid X Receptor (FXR)-Null Mice: FXR-Independent Suppression of Intestinal Bile Acid Absorption

Masaaki Miyata, Yoshiki Matsuda, Masahiro Nomoto, Yuki Takamatsu, Nozomi Sato, Mayumi Hamatsu, Paul A. Dawson, Frank J. Gonzalez and Yasushi Yamazoe
Drug Metabolism and Disposition February 1, 2009, 37 (2) 338-344; DOI: https://doi.org/10.1124/dmd.108.022590

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

Cholesterol Feeding Prevents Hepatic Accumulation of Bile Acids in Cholic Acid-Fed Farnesoid X Receptor (FXR)-Null Mice: FXR-Independent Suppression of Intestinal Bile Acid Absorption

Masaaki Miyata, Yoshiki Matsuda, Masahiro Nomoto, Yuki Takamatsu, Nozomi Sato, Mayumi Hamatsu, Paul A. Dawson, Frank J. Gonzalez and Yasushi Yamazoe
Drug Metabolism and Disposition February 1, 2009, 37 (2) 338-344; DOI: https://doi.org/10.1124/dmd.108.022590
Reddit logo Twitter logo Facebook logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Metabolic enzymes in nintedanib metabolism
  • Mechanism of AO Inactivation by Hydralazine
  • Warfarin PBPK modeling with target binding
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics