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Publication : Toosendanin inhibits adipogenesis by activating Wnt/β-catenin signaling.

First Author  Chen TX Year  2018
Journal  Sci Rep Volume  8
Issue  1 Pages  4626
PubMed ID  29545541 Mgi Jnum  J:262674
Mgi Id  MGI:6163253 Doi  10.1038/s41598-018-22873-x
Citation  Chen TX, et al. (2018) Toosendanin inhibits adipogenesis by activating Wnt/beta-catenin signaling. Sci Rep 8(1):4626
abstractText  Toosendanin (TSN), a triterpenoid extracted from Melia toosendan, has been reported to possess anti-oxidant, anti-inflammatory, anti-allergic, and anti-arthritic activities. However, its anti-adipogenic effect remains unknown. Here, we found that TSN dose-dependently attenuated lipid accumulation in preadipocytes 3T3-L1 as evidenced by Oil Red O staining. TSN also significantly downregulated mRNA and protein levels of adipocytokines (adiponectin and leptin), CCAAT/enhancer binding proteins alpha (C/EBP-alpha), peroxisome proliferator-activated receptor gamma (PPAR-gamma), fatty acid synthase, and acetyl-CoA carboxylase in adipocytes. To understand the mechanism, we observed that TSN effectively activated Wnt/beta-catenin pathway, in which TSN increased low density lipoprotein receptor related protein 6, disheveled 2, beta-catenin, and cyclin D1 expression levels, while it inactivated glycogen synthase kinase 3beta by enhancing its phosphorylation. Moreover, TSN reduced weight of gonadal white fat and serum triacylglycerol (TAG) content in high-fat diet (HFD)-fed mice. Interestingly, the in vivo studies also demonstrated that TSN promoted the expression of beta-catenin, but accordingly repressed C/EBP-alpha and PPAR-gamma expression in HFD-induced mice. Overall, TSN is capable of inhibiting the lipogenesis of adipocytes by activating the Wnt/beta-catenin pathway, suggesting potential application of TSN as a natural anti-obesity agent.
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