WntPathways

WntPathways - Wnt Signaling Pathways Show New Dimension of...

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Wnt Signaling Pathways Show New Dimension of Obesity Maya Hrachova NPB132 Professor Craig Warden
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2 INTRODUCTION Obesity is major medical problem that is characterized by an increase in number and size of mature fat cells (adipocytes) in the body. Adipocyte is a connective tissue cell that can differentiate and become specialized in the synthesis and storage of fat. Adipocytes play vital role in maintaining proper energy balance in the body, storing excess calories in a form of lipids and then making them available as an energy source under proper hormonal stimulation. Adipocytes can secrete signaling messengers (adipokines) that act as endocrine and paracrine factors and maintain whole body metabolism and homeostasis. Two main types of adipocytes exist: brown and white. White adipocytes primarily serve to store lipids while brown adipocytes function predominantly to dissipate energy in the form of heat [1]. Adipogenesis is a very complicated process that consists of two major phases. The first phase of adipogenesis is the fate determination, which involves the conversion of mesenchymal stem cells (MSC) to preadipocytes through a multi-step process. The second phase, known as terminal differentiation, is the process by which preadipocytes differentiate into adipocytes [2]. The differentiation of mesenchymal stem cells is regulated by both induction of various transcriptional activators and suppression of inhibitors. The transcriptional cascade that controls adipogenesis includes peroxisome proliferator-activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα). They are the chief regulators thought to coordinately direct the adipogenic program. PPARγ is both necessary and sufficient for preadipocyte deffirentiation, while C/EBPα appears to be important for the
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3 Hrachova acquisition of insulin sensitivity in adipocytes [3]. On the other hand, the extracellular signaling pathway Wnt is emerging as an important force that inhibits adipogenesis. Wnts are a family of autocrine and paracrine grows factors that are well known for regulating cell-to-cell interactions during embryogenesis and cancer. Wnts exert their effects by signaling through multiple pathways to control cell proliferation, survival, fate and behavior [1]. More recently, the Wnt signaling pathway members have been shown to inhibit differentiation of preadipocytes into adipocytes in cell culture and in mice models by inhibiting adipogenic transcription factors like C/EBPα and PPARγ. Plus, current studies suggest that Wnt signaling pathway members are linked to human obesity [3]. Wnt signaling pathway members emerge as very powerful suppressors of adipogenesis and understanding of their actions could be utilized for the development of new treatments for obesity. Therefore, highlighting the significance that Wnt signaling pathway play in the inhibition of adipogenesis will be the major focus of this paper. Wnt signaling inhibits adipogenesis in vitro
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This note was uploaded on 11/24/2011 for the course NPB 97952 taught by Professor ? during the Spring '09 term at UC Davis.

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WntPathways - Wnt Signaling Pathways Show New Dimension of...

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