Related Experiment Video
Updated: Apr 12, 2026
Robust Differentiation of Human iPSCs into a Pure Population of Adipocytes to Study Adipocyte-Associated Disorders
Published on: February 9, 2022
A cannabinoid receptor agonist N-arachidonoyl dopamine inhibits adipocyte differentiation in human mesenchymal stem
Seyeon Ahn1, Sodam Yi2, Won Jong Seo2
1Collge of Pharmacy ; Natural Products Research Institute, Seoul National University, Seoul 151-742.
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.
Insights
Endocannabinoids AEA and NADA differentially regulate adipogenesis in human bone marrow stem cells. AEA promotes differentiation via PPARγ activation, while NADA inhibits it through CB1 receptor signaling.
Area of Science:
- Cell Biology
- Molecular Biology
- Stem Cell Research
Background:
- Endocannabinoids interact with cellular targets including cannabinoid receptors (CB), TRPV1, and PPARγ.
- Adipocyte differentiation in hBM-MSCs involves increased expression of CB1 receptor, TRPV1, and PPARγ.
Purpose of the Study:
- To investigate the effects of AEA, NADA, and 2-AG on adipogenesis in hBM-MSCs.
- To elucidate the molecular mechanisms underlying endocannabinoid-mediated regulation of adipogenesis.
Main Methods:
- Treatment of hBM-MSCs with AEA, NADA, and 2-AG.
- Assessment of adipocyte differentiation.
- PPARγ transactivation assays.
- CB1 receptor antagonist (rimonabant) and TRPV1 antagonist (capsazepine) treatments.
Main Results:
- AEA promoted adipocyte differentiation, likely via direct PPARγ activation.
- NADA inhibited adipogenesis, an effect reversed by rimonabant (CB1 antagonist), suggesting CB1 receptor involvement.
- 2-AG at non-cytotoxic concentrations had no significant effect.
- Rimonabant alone promoted adipogenesis, indicating inverse agonism at CB1 receptors.
Conclusions:
- AEA and NADA exert opposing effects on adipogenesis in hBM-MSCs, mediated by distinct pathways.
- PPARγ activation by AEA promotes adipogenesis, while CB1 receptor signaling by NADA inhibits it.
- The CB1 receptor may constitutively suppress adipocyte differentiation in hBM-MSCs.
More Related Videos
10:50Author Spotlight: Isolation and Identification of Mesenchymal Stem Cells Derived from Adipose Tissue of Sprague Dawley Rats
Published on: April 7, 2023
13:26Visualization and Quantification of Mesenchymal Cell Adipogenic Differentiation Potential with a Lineage Specific Marker
Published on: March 31, 2018