title: A cannabinoid receptor agonist N-arachidonoyl dopamine inhibits adipocyte differentiation in human mesenchymal stem cells.
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 γ (PPARγ). The stimuli to induce adipocyte differentiation in hBM-MSCs increase the gene transcription of the CB1 receptor, TRPV1 and PPARγ. 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 PPARγ transactivation. AEA can directly activate PPARγ. The effect of AEA on PPARγ 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 PPARγ activity in the PPARγ 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 PPARγ activity inhibit adipogenesis in hBM-MSCs.
authors.affiliation: Collge of Pharmacy ; Natural Products Research Institute, Seoul National University, Seoul 151-742.
authors.forename: Seyeon
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Seoul Science High School, Seoul, 110-530.
authors.forename: Sodam
authors.initials: S
authors.lastname: Yi
authors.affiliation: Seoul Science High School, Seoul, 110-530.
authors.forename: Won Jong
authors.initials: WJ
authors.lastname: Seo
authors.affiliation: Seoul Science High School, Seoul, 110-530.
authors.forename: Myeong Jung
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Seoul Science High School, Seoul, 110-530.
authors.forename: Young Keun
authors.initials: YK
authors.lastname: Song
authors.affiliation: Seoul Science High School, Seoul, 110-530.
authors.forename: Seung Yong
authors.initials: SY
authors.lastname: Baek
authors.affiliation: Collge of Pharmacy.
authors.forename: Jinha
authors.initials: J
authors.lastname: Yu
authors.affiliation: Collge of Pharmacy ; Natural Products Research Institute, Seoul National University, Seoul 151-742.
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Hong
authors.affiliation: Collge of Pharmacy ; Natural Products Research Institute, Seoul National University, Seoul 151-742.
authors.forename: Jinyoung
authors.initials: J
authors.lastname: Lee
authors.affiliation: Bioscience Research Institute, Amorepacific Corporation R&D Center, Yongin 446-729, Republic of Korea.
authors.forename: Dong Wook
authors.initials: DW
authors.lastname: Shin
authors.affiliation: Collge of Pharmacy.
authors.forename: Lak Shin
authors.initials: LS
authors.lastname: Jeong
authors.affiliation: Collge of Pharmacy ; Natural Products Research Institute, Seoul National University, Seoul 151-742.
authors.forename: Minsoo
authors.initials: M
authors.lastname: Noh
keywords: Adipogenesis; Cannbinoid type 1 (CB1) receptor; Endocannabinoids; Human mesenchymal stem cells; Rimonabant