Figure 7

Schematic illustration of the effects of TSN on adipocyte cells differentiation. (A) In the absence of a Wnt signal, Dkk1 inhibits Wnt signaling by binding to co-receptors LRP. β-catenin is captured by a destruction complex that contains Axin and APC (adenomatous polyposis coli), which facilitates β-catenin phosphorylation by CKI and GSK3β. Then phosphorylated β-catenin is recognized by E3 ubiquitin ligase, which causes β-catenin to be degraded by the proteasome. (B) In TSN-stimulated cells, TSN enhances GSK3β phosphorylation, which results in β-catenin hypo-phosphorylation and its accumulation in cytoplasm. Additionally, TSN directly inhibits β-catenin ubiquitination, which also results in β-catenin accumulation in cytoplasm. Subsequently, β-catenin translocates into the nucleus and promotes the transcription of genes (such as CCD1) which inhibits adipogenic genes expression, such as C/EBP-α and PPAR-γ; FAS and ACC; adiponectin, and leptin. (C) On the other hand, TSN may activate the β-catenin promoter to enhance the β-catenin transcription, which results in overexpression of β-catenin mRNA.