Article: article from journal or magazin.
Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation.
European Journal of Pharmacology
We investigated the effects of anandamide on peroxisome proliferator-activated receptor gamma (PPARgamma) activity. In two different transactivation systems using either full-length or only the ligand binding domain of PPARgamma, we showed that anandamide, but not palmitoylethanolamide induced transcriptional activation of PPARgamma in a dose dependent manner with an EC50 of 8 microM. In addition, competition binding experiments showed that anandamide but not palmitoylethanolamide binds directly to PPAR-ligand binding domain. We also found that anandamide treatment induced 3T3-L1 fibroblast differentiation into adipocytes. Indeed, anandamide induced triglyceride droplet accumulation and the expression of PPARgamma responsive genes such as CCAAT enhancer binding protein alpha (C-EBPalpha), aP2, PerilipinA and Acrp30. Furthermore, the PPARgamma antagonist (GW9662) inhibited the anandamide-induced 3T3-L1 differentiation confirming that this is a PPARgamma-mediated process. Altogether, these data indicate that anandamide binds PPARgamma and induces cellular PPARgamma signaling.
3T3-L1 Cells, Adipocytes/cytology, Adipocytes/drug effects, Adiponectin, Anilides/pharmacology, Animals, Arachidonic Acids/metabolism, Arachidonic Acids/pharmacology, Binding Sites/genetics, Binding, Competitive/drug effects, Blotting, Western, CCAAT-Enhancer-Binding Protein-alpha/genetics, CCAAT-Enhancer-Binding Protein-alpha/metabolism, COS Cells, Cannabinoid Receptor Modulators/metabolism, Cannabinoid Receptor Modulators/pharmacology, Carrier Proteins, Cell Differentiation/drug effects, Cell Differentiation/genetics, Cell Line, Cercopithecus aethiops, Chromans/pharmacology, Dose-Response Relationship, Drug, Endocannabinoids, Fibroblasts/cytology, Fibroblasts/drug effects, Gene Expression/drug effects, HeLa Cells, Humans, Intercellular Signaling Peptides and Proteins/genetics, Intercellular Signaling Peptides and Proteins/metabolism, Luciferases/genetics, Luciferases/metabolism, Mice, PPAR gamma/genetics, PPAR gamma/metabolism, Phosphoproteins/genetics, Phosphoproteins/metabolism, Plasmids/genetics, Polyunsaturated Alkamides, Recombinant Fusion Proteins/genetics, Recombinant Fusion Proteins/metabolism, Reverse Transcriptase Polymerase Chain Reaction, Thiazolidinediones/pharmacology, Transcriptional Activation/drug effects, Transfection
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