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A Cannabinoid Receptor Agonist N-Arachidonoyl Dopamine Inhibits Adipocyte Differentiation in Human Mesenchymal Stem Cells
Biomolecules & Therapeutics ; : 218-224, 2015.
Article in English | WPRIM | ID: wpr-178042
ABSTRACT
Endocannabinoids can affect multiple cellular targets, such as cannabinoid (CB) receptors, transient receptor potential cation channel, subfamily V, member 1 (TRPV1) and peroxisome proliferator-activated receptor gamma (PPARgamma). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the CB1 receptor, TRPV1 and PPARgamma. In this study, the effects of three endocannabinoids, N-arachidonoyl ethanolamine (AEA), N-arachidonoyl dopamine (NADA) and 2-arachidonoyl glycerol (2-AG), on adipogenesis in hBM-MSCs were evaluated. The adipocyte differentiation was promoted by AEA whereas inhibited by NADA. No change was observed by the treatment of non-cytotoxic concentrations of 2-AG. The difference between AEA and NADA in the regulation of adipogenesis is associated with their effects on PPARgamma transactivation. AEA can directly activate PPARgamma. The effect of AEA on PPARgamma in hBM-MSCs may prevail over that on the CB1 receptor mediated signal transduction, giving rise to the AEA-induced promotion of adipogenesis. In contrast, NADA had no effect on the PPARgamma activity in the PPARgamma transactivation assay. The inhibitory effect of NADA on adipogenesis in hBM-MSCs was reversed not by capsazepine, a TRPV1 antagonist, but by rimonabant, a CB1 antagonist/inverse agonist. Rimonabant by itself promoted adipogenesis in hBM-MSCs, which may be interpreted as the result of the inverse agonism of the CB1 receptor. This result suggests that the constantly active CB1 receptor may contribute to suppress the adipocyte differentiation of hBM-MSCs. Therefore, the selective CB1 agonists that are unable to affect cellular PPARgamma activity inhibit adipogenesis in hBM-MSCs.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Signal Transduction / Dopamine / Felodipine / Transcriptional Activation / Adipocytes / Ethanolamine / Receptors, Cannabinoid / Receptor, Cannabinoid, CB1 / Endocannabinoids / PPAR gamma Limits: Humans Language: English Journal: Biomolecules & Therapeutics Year: 2015 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Signal Transduction / Dopamine / Felodipine / Transcriptional Activation / Adipocytes / Ethanolamine / Receptors, Cannabinoid / Receptor, Cannabinoid, CB1 / Endocannabinoids / PPAR gamma Limits: Humans Language: English Journal: Biomolecules & Therapeutics Year: 2015 Type: Article