GSK3‐activated STAT5 regulates expression of SFRPs to modulate adipogenesis

What is it about?

Obesity is a global health problem associated with an increased risk of type II diabetes and other metabolism related health problems. Dysfunction of adipocytes and dysregulation of adipocyte differentiation play critical roles in the development of obesity and its associated disorders. The function of adipocytes and the number of adipocytes in body fat depots is tightly associated with the process of adipogenesis which is controlled by many signaling molecules and transcription factors. The better understanding of the pathways that control adipogenesis will greatly contribute to the reduction of fat mass and protection from obesity and its associated diseases. Here, GSK3 is found to be essential to adipocyte differentiation through regulating both β-catenin dependent canonical Wnt pathway and non-canonical Wnt pathways which includes Wnt/planar cell polarity (PCP) pathway signaling via JNK, and Wnt/protein kinase C (PKC) pathway. The regulation of GSK3 on canonical pathway is mediated by STAT5/SFRP axis as demonstrated by our data that recombinant SFRP1 negatively regulates canonical Wnt/β-catenin signaling. And the effect of GSK3 on non-canonical Wnt pathway is mediated by JNK and RAC. Our findings identify a GSK3/STAT5/SFRPs/Wnt regulatory axis of adipogenesis and shed light on the molecular mechanism of adipogenesis by suggesting that different pathways and adipogenic regulators coordinately modulate adipocyte differentiation, which may provide some potential therapeutic targets for obesity and its associated metabolic disorders.

Featured Image