Curcumin-induced suppression of adipogenic differentiation is accompanied by activation of Wnt/beta-catenin signaling

Abstract

Curcumin, a polyphenol found in the rhizomes of Curcuma longa, improves obesity-associated inflammation and diabetes in obese mice. Curcumin also suppresses adipocyte differentiation, although the underlying mechanism remains unclear. Here, we used 3T3-L1 cells to investigate the details of the mechanism underlying the anti-adipogenic effects of curcumin. Curcumin inhibited mitogen-activated protein kinase (MAPK) (ERK, JNK, and p38) phosphorylation that was associated with differentiation of 3T3-L1 cells into adipocytes. During differentiation, curcumin also restored nuclear translocation of the integral Wnt signaling component beta-catenin in a dose-dependent manner. In parallel, curcumin reduced differentiation-stimulated expression of CK1alpha, GSK-3beta, and Axin, components of the destruction complex targeting beta-catenin. Accordingly, quantitative PCR analysis revealed that curcumin inhibited the mRNA expression of AP2 (mature adipocyte marker) and increased the mRNA expression of Wnt10b, Fz2 (Wnt direct receptor), and LRP5 (Wnt coreceptor). Curcumin also increased mRNA levels of c-Myc and cyclin D1, well-known Wnt targets. These results suggest that the Wnt signaling pathway participates in curcumin-induced suppression of adipogenesis in 3T3-L1 cells.