The Molecular Mechanism Of Pygo2in Inhibition Of Adipogenesis Through Wnt Signaling Pathway

Excessive intake without a relative expenditure in energy promotes adipocyte hyperplasia and adiposity. Adipocyte hyperplasia involves mesenchymal stem cells (MSCs) commitment to preadipocytes and preadipocytes differentiate into adipocyte which istriggered by signaling factors.MSCs,which reside in the vascular stroma of adipose tissue as well as in the bone marrow have the capacity to develop into several cell types including preadipocyte.BMP signaling pathway and Wnt signaling pathway are key mediators of stem cell commitment to preadipocyte.Following commitment,induction of growth-arrested preadipocytes with Insulin-like growth factor1(IGF1),glucocorticoid and cyclic AMP (cAMP) triggers DNA replication and reentry into cell cycle (mitotic clonal expansion).Once mitotic clonal expansion ceases, the cells acquire the appearance and features of adipocytes.Along this process,a transcription factor cascade is involved which followed by the expression of adipocyte genes. Critical to these events are phosphorylations of the transcription factor CCAAT enhancer binding protein β (C/EBPP) by MAP kinase and GSK3β to induce a conformational change that allows C/EBPβ to bind to DNA.Once C/EBPβ acquires DNA-binding activity,C/EBPa and PPAR y is transactivated by C/EBPβ which in turn coordinately activate genes whose expression produces the adipocyte phenotype.Wnt signaling pathway plays a central role in normal development and tumorigenesis.recent researchs indicated that Wnt signaling is a molecular switch that governs adipogenesis.Wnt signaling pathway maintains preadipocytes in an undifferentiated state through inhibition of the adipogenic transcription factors C/EBPα and PPAR γ.Nevertheless,after induction,control and Wntl-expessing cells showed a similar pattern of C/EBPβ.We first investigate the role of Pygo2which is an activated component of Wnt signaling pathway plays in the adipogenesis.The experimental results indicate that Pygo2inhibites adipogenesis through Wnt sinaling which lead us to explore the machnism of the inhibition of Wnt sinaling pathway in adipogenesis. Axin2,one of Wnt sinaling targetgenes is first been verified for its activity to combine GSK3β,which onceis activated by Wnt signaling pathay in3T3-L1will recruit GSK3β from nucleus to cytoplasm. The phosphorylation of C/EBPβ by GSK3(3will be preventedsince the relocation of GSK3β from nucleus to cytoplasm, which then suppress the DNA-binding activity of C/EBPβ as well as the transcription of C/EBP a and PPAR γ.Thus, Wnt signaling pathway eventually inhibite adipogenesis.