Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation.
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.
SANOFI-SYNTHELABO RECHERCHE, Oncology Department, 371 rue du Prof. Blayac, F-34184 Montpellier Cedex 04, France.
Monsif
M
Bouaboula
Sandrine
S
Hilairet
Jean
J
Marchand
Lluis
L
Fajas
Gerard
G
Le Fur
Pierre
P
Casellas
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D052242:Adiponectin; D000813:Anilides / Q000494:pharmacology; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001665:Binding Sites / Q000235:genetics; D001667:Binding, Competitive / Q000187:drug effects; D015153:Blotting, Western; D022763:CCAAT-Enhancer-Binding Protein-alpha / Q000235:genetics / Q000378:metabolism; D019556:COS Cells; D063385:Cannabinoid Receptor Modulators / Q000378:metabolism / Q000494:pharmacology; D002352:Carrier Proteins; D002454:Cell Differentiation / Q000187:drug effects* / Q000235:genetics; D002460:Cell Line; D002522:Chlorocebus aethiops; D002839:Chromans / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D063388:Endocannabinoids; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D047495:PPAR gamma / Q000235:genetics* / Q000378:metabolism; D000070778:Perilipin-1; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D000077205:Pioglitazone; D010957:Plasmids / Q000235:genetics; D053284:Polyunsaturated Alkamides; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D045162:Thiazolidinediones / Q000494:pharmacology; D015533:Transcriptional Activation / Q000187:drug effects*; D014162:Transfection; D000077288:Troglitazone
C457499:2-chloro-5-nitrobenzanilide; D052242:Adiponectin; D000813:Anilides; D001095:Arachidonic Acids; D022763:CCAAT-Enhancer-Binding Protein-alpha; D063385:Cannabinoid Receptor Modulators; D002352:Carrier Proteins; D002839:Chromans; D063388:Endocannabinoids; D036341:Intercellular Signaling Peptides and Proteins; D047495:PPAR gamma; D000070778:Perilipin-1; D010750:Phosphoproteins; D053284:Polyunsaturated Alkamides; D011993:Recombinant Fusion Proteins; D045162:Thiazolidinediones; D008156:Luciferases; D000077288:Troglitazone; C078814:anandamide; D000077205:Pioglitazone