A Cannabinoid Receptor Agonist N-Arachidonoyl Dopamine Inhibits Adipocyte Differentiation in Human Mesenchymal Stem Cells

作者：Ahn Seyeon; Yi Sodam; Seo Won Jong; Lee Myeong Jung; Song Young Keun; Baek Seung Yong; Yu Jinha; Hong Soo Hyun; Lee Jinyoung; Shin Dong Wook; Jeong Lak Shin; Noh Minsoo^*

来源：Biomolecules & Therapeutics, 2015, 23(3): 218-224.

DOI：10.4062/biomolther.2014.137

• Endocannabinoids
• Cannbinoid type 1 (CB1) receptor
• Adipogenesis
• Human mesenchymal stem cells
• Rimonabant

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 (PPAR gamma). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the CB1 receptor, TRPV1 and PPAR gamma. 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 PPAR gamma transactivation. AEA can directly activate PPAR gamma. The effect of AEA on PPAR gamma 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 PPAR gamma activity in the PPAR gamma 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 PPAR gamma activity inhibit adipogenesis in hBM-MSCs.

• 出版日期2015-5-1