Inhibition of Adipogenesis by Wnt Signaling

• DOI: 10.1126/science.289.5481.950
• Publication Date: 2002-07-27T09:48:21Z
• Authors: Sarah E. Ross; Nahid Hemati; Kenneth A. Longo; Christina N. Bennett; Peter C. Lucas; Robin L. Erickson; Ormond A. MacDougald
• Keywords: 0303 health sciences; Muscles; Genetic Vectors; Gene Transfer Techniques; Mice, Nude; Nuclear Proteins; Proteins; Receptors, Cytoplasmic and Nuclear; Cell Differentiation; 3T3 Cells; DNA-Binding Proteins; Mesoderm; Repressor Proteins; Cytoskeletal Proteins; Mice; 03 medical and health sciences; Axin Protein; Proto-Oncogene Proteins; Adipocytes; CCAAT-Enhancer-Binding Proteins; Animals; Cell Lineage

Wnts are secreted signaling proteins that regulate developmental processes. Here we show that Wnt signaling, likely mediated by Wnt-10b, is a molecular switch that governs adipogenesis. Wnt signaling maintains preadipocytes in an undifferentiated state through inhibition of the adipogenic transcription factors CCAAT/enhancer binding protein α (C/EBPα) and peroxisome proliferator- activated receptor γ (PPARγ). When Wnt signaling in preadipocytes is prevented by overexpression of Axin or dominant-negative TCF4, these cells differentiate into adipocytes. Disruption of Wnt signaling also causes transdifferentiation of myoblasts into adipocytes in vitro, highlighting the importance of this pathway not only in adipocyte differentiation but also in mesodermal cell fate determination.