The anti-adipogenic effects of (-)epigallocatechin gallate are dependent on the WNT/beta-catenin pathway

Abstract

(-)Epigallocatechin gallate (EGCG) is the most abundant catechin in green tea and reportedly has anti-obesity and anti-adipogenic effects. In this study, we determined that the up-regulation of the WNT/beta-catenin pathway is the anti-adipogenic mechanisms of EGCG in 3T3-L1 cells. EGCG treatment down-regulates the expression of major genes involved in the adipogenesis pathway including peroxisome proliferator-activated receptor (PPAR)gamma, CCAAT/enhancer binding protein (C/EBP)alpha, fatty acid binding protein (FABP)4 and fatty acid synthase (FASN), while up-regulating the nuclear level of beta-catenin. Knockdown of beta-catenin using small interfering (si) RNA attenuated the inhibitory effects of EGCG on intracellular lipid accumulation. beta-catenin siRNA transfection also recovered terminal adipocyte markers such as FABP4, FASN, lipoprotein lipase and adiponectin, which were down-regulated by EGCG. The DNA binding activities as well as the expression levels of PPAR gamma and C/EBP alpha, which were down-regulated by EGCG, were significantly restored by beta-catenin siRNA transfection. In addition, we found that EGCG efficiently up-regulates the WNT/beta-catenin pathway. Among the members of the WNT/beta-catenin pathway, the expressions of low density lipoprotein receptor-related protein (LRP)5, LRP6, disheveled (DVL)2 and DVL3 were significantly up-regulated, while AXIN expression was down-regulated by EGCG, and the phosphorylation of glycogen synthase kinase 3 beta was increased. These results suggest that EGCG activates the WNT/beta-catenin pathway, resulting in the up-regulation of beta-catenin, which down-regulates the major genes of the adipogenesis pathway. Taken together, our findings clearly show that the anti-adipogenic effects of EGCG are, at least partially, dependent on the WNT/beta-catenin pathway. (C) 2013 Elsevier Inc. All rights reserved.