Abstract
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.
MeSH terms
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3T3-L1 Cells
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Adipocytes / cytology
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Adipocytes / drug effects*
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Adipocytes / metabolism
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Adiponectin
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Anilides / pharmacology
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Animals
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Arachidonic Acids / metabolism
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Arachidonic Acids / pharmacology*
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Binding Sites / genetics
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Binding, Competitive / drug effects
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Blotting, Western
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CCAAT-Enhancer-Binding Protein-alpha / genetics
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CCAAT-Enhancer-Binding Protein-alpha / metabolism
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COS Cells
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Cannabinoid Receptor Modulators / metabolism
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Cannabinoid Receptor Modulators / pharmacology
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Carrier Proteins
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Cell Differentiation / drug effects*
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Cell Differentiation / genetics
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Cell Line
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Chlorocebus aethiops
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Chromans / pharmacology
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Dose-Response Relationship, Drug
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Endocannabinoids
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Fibroblasts / cytology
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Fibroblasts / drug effects
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Fibroblasts / metabolism
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Gene Expression / drug effects
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HeLa Cells
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Humans
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Intercellular Signaling Peptides and Proteins / genetics
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Intercellular Signaling Peptides and Proteins / metabolism
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Luciferases / genetics
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Luciferases / metabolism
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Mice
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PPAR gamma / genetics*
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PPAR gamma / metabolism
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Perilipin-1
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Phosphoproteins / genetics
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Phosphoproteins / metabolism
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Pioglitazone
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Plasmids / genetics
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Polyunsaturated Alkamides
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Recombinant Fusion Proteins / genetics
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Thiazolidinediones / pharmacology
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Transcriptional Activation / drug effects*
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Transfection
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Troglitazone
Substances
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2-chloro-5-nitrobenzanilide
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Adiponectin
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Anilides
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Arachidonic Acids
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CCAAT-Enhancer-Binding Protein-alpha
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Cannabinoid Receptor Modulators
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Carrier Proteins
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Chromans
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Endocannabinoids
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Intercellular Signaling Peptides and Proteins
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PPAR gamma
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Perilipin-1
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Phosphoproteins
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Polyunsaturated Alkamides
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Recombinant Fusion Proteins
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Thiazolidinediones
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Luciferases
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Troglitazone
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anandamide
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Pioglitazone