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

Lipids in Health and Disease

Research

Andrew J Bennett¹  Mauro Dionisi²  Stephen PH Alexander³ 

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

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

DOI  :  10.1186/1476-511X-11-51

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

来源: Springer

【 摘 要 】

BackgroundOleamide (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.ResultsActivation 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.ConclusionsWe 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】

Unknown   
© Dionisi et al.; licensee BioMed Central Ltd. 2012. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.