Anandamide induced PPARγ transcriptional activation and 3T3-L1 preadipocyte differentiation

We investigated the effects of anandamide on peroxisome proliferator-activated receptor gamma (PPAR-y) activity. In two different transactivation systems using either full-length or only the ligand binding domain of PPAR-y, we showed that anandamide, but not palmitoylethanolamide induced transcriptional activation of PPAR-y in a dose dependent manner with an EC50 of 8 mu M. In addition, competition binding experiments showed that anandamide but not palmitoylethanolamide binds directly to PTAR-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 PPAR-y responsive genes such as CCAAT enhancer binding protein alpha (C-EBP alpha), aP2, PerilipinA and Acrp30. Furthermore, the PPAR gamma antagonist (GW9662) inhibited the anandamide-induced 3T3-L1 differentiation confirming that this is a PPAR gamma-mediated process. Altogether, these data indicate that anandamide binds PPAR gamma and induces cellular PPAR gamma signaling. (c) 2005 Elsevier B.V. All rights reserved.