Fig. 4
From: Signaling pathways in obesity: mechanisms and therapeutic interventions
Wnt/β-catenin pathways in obesity pathogenesis. In the canonical Wnt pathway, upon activation by Wnt proteins, β-catenin is released and enters the nucleus as a transcription coactivator of TCF to regulate the transcription of target genes. The activation of Wnt/β-catenin pathway leads to, (1) the supersession of adipogenesis by down-regulating the expression of PPARγ, C1EBPα, Add1, APM, etc.; (2) the inhibition of BAT-related thermogenesis by down-regulating UCP-1; and (3) the increase of insulin sensitivity by down-regulating GSK3β expression in CNS while up-regulating incretins within the small intestinal epithelium. The canonical Wnt signaling can be stimulated by factors including leptin, OSBPL2, and miRNAs like miR-23b, miR-148b miR-4269, and miR-4429. It can also be inhibited by JAK/STAT3 pathway, CXXC5, and NOTUM. These factors are all involved in the pathogenesis of obesity by regulating Wnt/β-catenin signaling pathway. Additionally, Wnt5a, a part of the non-canonical Wnt pathway, induces obesity-associated inflammation in WAT in a JNK-dependent manner, which further contributes to the occurrence of insulin resistance in adipose tissue
