Inhibition of Adipogenesis by Wnt Signaling

• Published in: Science (American Association for the Advancement of Science) Vol. 289; no. 5481; pp. 950 - 953
• Main Authors: Ross, Sarah E., Hemati, Nahid, Longo, Kenneth A., Bennett, Christina N., Lucas, Peter C., Erickson, Robin L., MacDougald, Ormond A.
• Format: Journal Article
• Language: English
• Published: Washington, DC American Society for the Advancement of Science 11.08.2000; American Association for the Advancement of Science
• Subjects: 3T3 Cells; 3T3 L1 cells; Adipocytes; Adipocytes - cytology; Adipocytes - metabolism; adipogenesis; Analysis; Animals; Axin Protein; beta Catenin; Biological and medical sciences; C/EBP^a protein; CCAAT-Enhancer-Binding Proteins; CCAAT/enhancer binding protein ^a; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell lines; Cell physiology; Cell research; Cellular differentiation; Cytological research; Cytoskeletal Proteins - metabolism; DNA-Binding Proteins - antagonists & inhibitors; DNA-Binding Proteins - genetics; DNA-Binding Proteins - metabolism; Fat cells; Fundamental and applied biological sciences. Psychology; Gene Transfer Techniques; Genetic Vectors; Lipogenesis; Mesoderm - cytology; Mice; Mice, Nude; Molecular and cellular biology; Muscles - cytology; Muscles - metabolism; Myoblasts; NIH 3T3 cells; Nuclear Proteins - antagonists & inhibitors; Nuclear Proteins - genetics; Nuclear Proteins - metabolism; peroxisome proliferator-activated receptor ^g; PPAR^g protein; Proteins - genetics; Proteins - metabolism; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins - metabolism; Receptors, Cytoplasmic and Nuclear - antagonists & inhibitors; Receptors, Cytoplasmic and Nuclear - genetics; Receptors, Cytoplasmic and Nuclear - metabolism; Repressor Proteins; Retroviridae; Retroviridae - genetics; Retroviridae - physiology; Signal Transduction; Synapses; TCF Transcription Factors; Trans-Activators; Transcription Factor 7-Like 2 Protein; Transcription Factors - antagonists & inhibitors; Transcription Factors - genetics; Transcription Factors - metabolism; Wnt Proteins; Wnt-10b protein; Zebrafish Proteins; Adipocyte; Signal transduction; Vertebrata; Mammalia; Adipose tissue; Development; Gene overexpression; Developmental stage; Cell differentiation; Transcription factor; Protein
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.289.5481.950

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.