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

Lipids in Health and Disease

Andrew J Bennett¹  Stephen PH Alexander¹  Mauro Dionisi² 

[1] School of Biomedical Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, England;Current address: Istituto Italiano di Tecnologia, via Morego, Genova, Italy

关键词: Endocannabinoids;    PPAR;    Peroxisome proliferator;    Oleamide;   

Others  :  1160312
DOI  :  10.1186/1476-511X-11-51

 received in 2012-04-03, accepted in 2012-05-14,  发布年份 2012

【 摘 要 】

Background

Oleamide (ODA) is a fatty acid primary amide first identified in the cerebrospinal fluid of sleep-deprived cats, which exerts effects on vascular and neuronal tissues, with a variety of molecular targets including cannabinoid receptors and gap junctions. It has recently been reported to exert a hypolipidemic effect in hamsters. Here, we have investigated the nuclear receptor family of peroxisome proliferator-activated receptors (PPARs) as potential targets for ODA action.

Results

Activation of PPARα, PPARβ and PPARγ was assessed using recombinant expression in Chinese hamster ovary cells with a luciferase reporter gene assay. Direct binding of ODA to the ligand binding domain of each of the three PPARs was monitored in a cell-free fluorescent ligand competition assay. A well-established assay of PPARγ activity, the differentiation of 3T3-L1 murine fibroblasts into adipocytes, was assessed using an Oil Red O uptake-based assay. ODA, at 10 and 50 μM, was able to transactivate PPARα, PPARβ and PPARγ receptors. ODA bound to the ligand binding domain of all three PPARs, although complete displacement of fluorescent ligand was only evident for PPARγ, at which an IC₅₀ value of 38 μM was estimated. In 3T3-L1 cells, ODA, at 10 and 20 μM, induced adipogenesis.

Conclusions

We have, therefore, identified a novel site of action of ODA through PPAR nuclear receptors and shown how ODA should be considered as a weak PPARγ ligand in vitro.

【 授权许可】

   
2012 Dionisi et al.; licensee BioMed Central Ltd.

【 图 表 】

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