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Oleamide activates peroxisome proliferator-activated receptor gamma (PPARγ) in vitro

Mauro Dionisi1, Stephen P H Alexander, Andrew J Bennett

  • 1FRAME Laboratory, School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, England.

Lipids in Health and Disease
|May 16, 2012
PubMed
Abstract

Insights

Oleamide (ODA) activates peroxisome proliferator-activated receptors (PPARs), including PPARγ, and promotes adipogenesis. This study identifies PPARs as novel targets for ODA, suggesting its potential as a weak PPARγ ligand.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Endocrinology

Background:

  • Oleamide (ODA), a fatty acid amide found in cerebrospinal fluid, impacts vascular and neuronal tissues.
  • ODA exhibits effects on cannabinoid receptors and gap junctions.
  • Previous studies indicated a hypolipidemic effect of ODA in hamsters.

Purpose of the Study:

  • To investigate peroxisome proliferator-activated receptors (PPARs) as potential molecular targets for Oleamide (ODA).
  • To determine if ODA interacts with and activates PPARα, PPARβ, and PPARγ.
  • To assess ODA's effect on adipogenesis, a known PPARγ-mediated process.

Main Methods:

  • Recombinant expression of PPARα, PPARβ, and PPARγ in Chinese hamster ovary cells.
  • Luciferase reporter gene assay to measure receptor transactivation.
  • Cell-free fluorescent ligand competition assay for direct ODA binding to PPARs.
  • 3T3-L1 murine fibroblast differentiation assay (Oil Red O uptake) to assess PPARγ activity.

Main Results:

  • Oleamide (ODA) transactivated PPARα, PPARβ, and PPARγ at concentrations of 10 and 50 μM.
  • ODA demonstrated direct binding to the ligand-binding domain of all three PPAR subtypes.
  • ODA showed a significant effect on PPARγ, with an estimated IC50 of 38 μM, and induced adipogenesis in 3T3-L1 cells at 10 and 20 μM.

Conclusions:

  • Peroxisome proliferator-activated receptors (PPARs) are identified as novel molecular targets for Oleamide (ODA).
  • Oleamide (ODA) functions as a weak ligand for PPARγ in vitro.
  • The findings provide new insights into the molecular mechanisms underlying ODA's biological effects.

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