Rotenoisin A is a Novel Anti-Adipogenic Compound
Environmental Health Science
The purpose of this study was to investigate the mechanisms underlying the inhibitory effects of rotenoisin A on adipogenesis in 3T3-L1 preadipocytes. 3T3-L1 cells were treated with rotenoisin A for 8days after the induction of differentiation. Oil-red O staining showed that rotenoisin A significantly inhibited DMI-induced lipid accumulation and adipocyte differentiation. We found that rotenoisin A treatment of 3T3-L1 preadipocytes significantly reduced the mRNA and protein levels of the key adipocyte-specific transcription factors C/EBPbeta, C/EBPalpha, and PPARgamma and markedly inhibited the expression of fatty acid-binding protein (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL). Furthermore, we observed that rotenoisin A substantially increased the phosphorylation of AMP-activated protein kinase (AMPK) and its downstream target phosphorylated acetyl CoA carboxylase (ACC). However, co-treatment with Compound C, an AMPK inhibitor, reversed the rotenoisin A-induced inhibition of the expression of the adipogenic transcription factors C/EBPalpha and PPARgamma and decreased the levels of phosphorylated AMPK in differentiated 3T3-L1 cells. These results demonstrated that the anti-adipogenesis mechanism involves the down-regulation of critical adipogenic transcription factors, including C/EBPbeta, C/EBPalpha, and PPARgamma, through activation of the AMPK signaling pathway by rotenoisin A.
Cho, H., Park, H., Jang, S., Won, C., Kim, H., Kim, T., & Cho, J. (2019). Rotenoisin A is a Novel Anti-Adipogenic Compound. Bioorganic & Medicinal Chemistry Letters, 29 (1), 89-96. https://doi.org/10.1016/j.bmcl.2018.11.008