Video 1-Showing representation of Wnt/β-Catenin signaling pathway ,including factors that affects its growth and development. Wnt proteins signal vital process in embryonic development. Courtesy of JJ medicine at https://www.youtube.com/watch?v=NGVP4J9jpgs.
Adipogenesis is the development process of adipocyte.It involves various signaling such as Wnt/β and Notch signaling pathway. These involves communications between protein receptors, secondary messages and ligand such as growth factor β, interleukin 17, growth factor 1 (IGF1), activin.(
Figure 1-Showing the overview of Adipogenesis and the various signaling pathways involved .Courtesy of http://jcs.biologists.org/content/124/16/2681.
Obesity can be studied by determining the role of Wnt/β-catenin signaling pathway. Wnt/β-catenin signaling pathway is involved in maintaining balance in conditions in developed cells b controlling cell differentiation, increase in number and its stability.If there was any mutation in any part of the proteins and secondary messengers involved in adipogenesis, it might lead to cancer, neurodegeneration and osteoporosis. The complexity of the cascading signally pathway has lead to more research to find link between obesity and Wnt/β-catenin signaling.
The Wnt/β-catenin signaling was discovered in 1982 in as the Wnt1 gene in mice which regulated the formation of wings , which led to further discovery of the Wnt/β-catenin signaling. Cysteine-rich Wnt proteins produce ligands( ie 40 kDa glycoproteins) that initiate signaling involving receptors that control cofactor β-catenin’s transcription activities. We studied about β-catenin interacting with cadherins and transmit signals to the cytoplasm. Wnts regulates and stabilize β-catenin . Factors such as growth factor, protein kinase A influences the activity of β- catenin.(Chen et al., 2003)
Figure 2- Digram representing the Wnt/β-catenin signaling in Adipogenesis.Courtesy of Wnt proteins work with LRP, FZD, Wnt-FZD-LRP5/6 complex in regulating β-catenin by preventing it’s phosphorylation. When β-catenin enters the nucleus, and turns on transcription via binding to members of the lymphoid enhancer factor (TCF/LEF) family of transcription factors. ZNRF3/RNF43 is a negative feedback regulator of Wnt/β-catenin signaling. With a lack of R-spondin proteins (RSPOs), ZNRF3/RNF43 is recruited by DVL to Wnt-FZD-LRP5/6 complex to mediate their degradation (left panel). RSPO’s presence together with ZNRF3/RNF43 and LGR4/5/6, leads to addition of ubiquinine, endocytosis of ZNRF3/RNF43
Wnts phosphorylates β- catenin by using the activities of seven-Transmembrane receptors, protein 5 (LRP5) , Frizzled (FZD) ,seven-Transmembrane receptors as Wnt-FZD-LRP5/6 complex. (Chen et al., 2003). Then β- catenin binds to lymphoid enhancer factor (TCF/LEF by entering the nucleus thus becoming a transcription factor.(Figure 2)
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