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DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat
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DNBS/TNBS Colitis Models: Providing Insights Into Inflammatory Bowel Disease and Effects of Dietary Fat

Published on: February 27, 2014

13-Oxo-ODE is an endogenous ligand for PPARgamma in human colonic epithelial cells

Reinhold Altmann1, Martin Hausmann, Tanja Spöttl

  • 1Department of Internal Medicine I, University of Regensburg, 93042 Regensburg, Germany.

Biochemical Pharmacology
|July 3, 2007
PubMed
Abstract

Insights

A novel compound, 13-Oxo-ODE, derived from linoleic acid metabolism in colonic epithelial cells (CECs), directly binds to peroxisome proliferator-activated receptor gamma (PPARgamma). This interaction demonstrates anti-inflammatory effects, suggesting 13-HODE dehydrogenase as a potential therapeutic target for inflammatory bowel disease (IBD).

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Gastroenterology

Background:

  • Peroxisome proliferator-activated receptor gamma (PPARgamma) activation ameliorates colitis in inflammatory bowel disease (IBD) models.
  • Reduced PPARgamma expression is observed in ulcerative colitis patients.
  • 13-HODE and 15-HETE are endogenous PPARgamma ligands derived from 12/15-lipoxygenase (LOX).

Purpose of the Study:

  • To investigate if 13-Oxo-ODE, a metabolite of 13-HODE, is a novel endogenous ligand for PPARgamma in colonic epithelial cells (CECs).
  • To explore the anti-inflammatory potential of 13-Oxo-ODE in the context of IBD.

Main Methods:

  • Investigated LOX activity and 13-HODE dehydrogenase in CECs after stimulation with linoleic acid.
  • Identified LOX metabolites using RP-18 reversed-phase HPLC.
  • Demonstrated binding of (14)C-labelled 13-Oxo-ODE to His-tagged PPARgamma.

Main Results:

  • High amounts of 13-Oxo-ODE were formed in CECs upon stimulation of linoleic acid metabolism.
  • 13-Oxo-ODE exhibited a more pronounced decrease in IL-8 secretion than troglitazone and known PPARgamma ligands.
  • Binding assays confirmed direct interaction between 13-Oxo-ODE and PPARgamma.

Conclusions:

  • 13-Oxo-ODE can be induced in CECs and binds to PPARgamma.
  • 13-Oxo-ODE possesses anti-inflammatory properties.
  • 13-HODE dehydrogenase presents a potential therapeutic target for IBD.

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