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Eur J Pharmacol. 2005 Jul 11;517(3):174-81.

Anandamide induced PPARgamma transcriptional activation and 3T3-L1 preadipocyte differentiation.

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1
SANOFI-SYNTHELABO RECHERCHE, Oncology Department, 371 rue du Prof. Blayac, F-34184 Montpellier Cedex 04, France.

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.

PMID:
15987634
DOI:
10.1016/j.ejphar.2005.05.032
[Indexed for MEDLINE]

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