Cinnamaldehyde combined with 18β-glycyrrhetinic acid promotes the differentiation of C3H10T1/2 MSCs into thermogenic adipocytes through PGC1α/FNDC5/UCP1 pathway

Finding bioactive substances that can promote the de novo differentiation of stem cells into thermogenic adipocytes is a promising anti-obesity strategy. Cinnamaldehyde (CM) and 18β-glycyrrhetinic acid (GA) are the main active ingredients in Chinese herbal medicine. In this study, C3H10T1/2 mesenchymal stem cells (MSCs) were used to investigate whether CM and GA could promote the differentiation of MSCs into thermogenic adipocytes and the possible molecular mechanism. The experimental results demonstrated that CM and GA could promote the mRNA expression of adipogenic transcription factors Pparγ, Cebpα and Cebpβ, as well as thermogenic adipocyte-specific markers Pgc1α and Ucp1. CM combined with GA further enhanced these effects. CM/GA alone or in combination could increase the expression of FNDC5 mRNA and protein. After transfection with FNDC5 siRNA, the mRNA and protein levels of FNDC5 and UCP1 were significantly decreased, while the levels of PGC1α did not change apparently. After the combination of CM and GA intervention, the levels of FNDC5 and UCP1 were slightly restored, but could not return to the normal level. In conclusion, CM and GA could promote the differentiation of C3H10T1/2 MSCs into thermogenic adipocytes, and their combination could enhance this effect, which may be mediated by PGC1α/FNDC5/UCP1 signalling pathway.