Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Author's Takes
  • Reviews
    • View all reviews ...
    • Aging (Jul 2022)
    • Next-Generation Sequencing in Medicine (Jun 2022)
    • New Therapeutic Targets in Cardiovascular Diseases (Mar 2022)
    • Immunometabolism (Jan 2022)
    • Circadian Rhythm (Oct 2021)
    • Gut-Brain Axis (Jul 2021)
    • Tumor Microenvironment (Mar 2021)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Commentaries
    • Concise Communication
    • Editorials
    • Viewpoint
    • Top read articles
  • Clinical Medicine
  • JCI This Month
    • Current issue
    • Past issues

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Author's Takes
  • In-Press Preview
  • Commentaries
  • Concise Communication
  • Editorials
  • Viewpoint
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Alerts
  • Advertising
  • Job board
  • Subscribe
  • Contact
Top
  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal
  • Top
  • Abstract
  • Version history
  • Article usage
  • Citations to this article

Advertisement

Research Article Free access | 10.1172/JCI118118

Fibrates increase human apolipoprotein A-II expression through activation of the peroxisome proliferator-activated receptor.

N Vu-Dac, K Schoonjans, V Kosykh, J Dallongeville, J C Fruchart, B Staels, and J Auwerx

U.325 INSERM, Département d'Athérosclérose, Institut Pasteur, Lille, France.

Find articles by Vu-Dac, N. in: JCI | PubMed | Google Scholar

U.325 INSERM, Département d'Athérosclérose, Institut Pasteur, Lille, France.

Find articles by Schoonjans, K. in: JCI | PubMed | Google Scholar

U.325 INSERM, Département d'Athérosclérose, Institut Pasteur, Lille, France.

Find articles by Kosykh, V. in: JCI | PubMed | Google Scholar

U.325 INSERM, Département d'Athérosclérose, Institut Pasteur, Lille, France.

Find articles by Dallongeville, J. in: JCI | PubMed | Google Scholar

U.325 INSERM, Département d'Athérosclérose, Institut Pasteur, Lille, France.

Find articles by Fruchart, J. in: JCI | PubMed | Google Scholar

U.325 INSERM, Département d'Athérosclérose, Institut Pasteur, Lille, France.

Find articles by Staels, B. in: JCI | PubMed | Google Scholar

U.325 INSERM, Département d'Athérosclérose, Institut Pasteur, Lille, France.

Find articles by Auwerx, J. in: JCI | PubMed | Google Scholar

Published August 1, 1995 - More info

Published in Volume 96, Issue 2 on August 1, 1995
J Clin Invest. 1995;96(2):741–750. https://doi.org/10.1172/JCI118118.
© 1995 The American Society for Clinical Investigation
Published August 1, 1995 - Version history
View PDF
Abstract

In view of the evidence linking plasma high density lipoprotein (HDL)-cholesterol levels to a protective effect against coronary artery disease and the widespread use of fibrates in the treatment of hyperlipidemia, the goal of this study was to analyze the influence of fibrates on the expression of apolipoprotein (apo) A-II, a major protein constituent of HDL. Administration of fenofibrate (300 mg/d) to 16 patients with coronary artery disease resulted in a marked increase in plasma apo A-II concentrations (0.34 +/- 0.11 to 0.45 +/- 0.17 grams/liter; P < 0.01). This increase in plasma apo A-II was due to a direct effect on hepatic apo A-II production, since fenofibric acid induced apo A-II mRNA levels to 450 and 250% of control levels in primary cultures of human hepatocytes and in human hepatoblastoma HepG2 cells respectively. The induction in apo A-II mRNA levels was followed by an increase in apo A-II secretion in both cell culture systems. Transient transfection experiments of a reporter construct driven by the human apo A-II gene promoter indicated that fenofibrate induced apo A-II gene expression at the transcriptional level. Furthermore, several other peroxisome proliferators, such as the fibrate, Wy-14643, and the fatty acid, eicosatetraynoic acid (ETYA), also induced apo A-II gene transcription. Unilateral deletions and site-directed mutagenesis identified a sequence element located in the J-site of the apo A-II promoter mediating the responsiveness to fibrates and fatty acids. This element contains two imperfect half sites spaced by 1 oligonucleotide similar to a peroxisome proliferator responsive element (PPRE). Cotransfection assays showed that the peroxisome proliferator activated receptor (PPAR) transactivates the apo A-II promoter through this AII-PPRE. Gel retardation assays demonstrated that PPAR binds to the AII-PPRE with an affinity comparable to its binding affinity to the acyl coA oxidase (ACO)-PPRE. In conclusion, in humans fibrates increase plasma apo A-II concentrations by inducing hepatic apo A-II production. Apo A-II expression is regulated at the transcriptional level by fibrates and fatty acids via the interaction of PPAR with the AII-PPRE, thereby demonstrating the pivotal role of PPAR in controlling human lipoprotein metabolism.

Images.

Browse pages

Click on an image below to see the page. View PDF of the complete article

icon of scanned page 741
page 741
icon of scanned page 742
page 742
icon of scanned page 743
page 743
icon of scanned page 744
page 744
icon of scanned page 745
page 745
icon of scanned page 746
page 746
icon of scanned page 747
page 747
icon of scanned page 748
page 748
icon of scanned page 749
page 749
icon of scanned page 750
page 750
Version history
  • Version 1 (August 1, 1995): No description

Article tools

  • View PDF
  • Download citation information
  • Send a comment
  • Share this article
  • Terms of use
  • Standard abbreviations
  • Need help? Email the journal

Metrics

  • Article usage
  • Citations to this article

Go to

  • Top
  • Abstract
  • Version history
Advertisement
Advertisement

Copyright © 2022 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts