Inhibition of adipogenesis by Wnt signaling.
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 alpha (C/EBPalpha) and peroxisome proliferator- activated receptor gamma (PPARgamma). 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.
Department of Physiology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109-0622, USA.
S E
SE
Ross
N
N
Hemati
K A
KA
Longo
C N
CN
Bennett
P C
PC
Lucas
R L
RL
Erickson
O A
OA
MacDougald
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism*; D000818:Animals; D060466:Axin Protein; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation; D019070:Cell Lineage; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D018014:Gene Transfer Techniques; D005822:Genetic Vectors; D008648:Mesoderm / Q000166:cytology; D051379:Mice; D008819:Mice, Nude; D009132:Muscles / Q000166:cytology / Q000378:metabolism; D009687:Nuclear Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D018160:Receptors, Cytoplasmic and Nuclear / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins; D012190:Retroviridae / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction; D051820:TCF Transcription Factors; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D051153:Wnt Proteins; D029961:Zebrafish Proteins; D051176:beta Catenin
D060466:Axin Protein; D022762:CCAAT-Enhancer-Binding Proteins; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D011506:Proteins; D011518:Proto-Oncogene Proteins; D018160:Receptors, Cytoplasmic and Nuclear; D012097:Repressor Proteins; D051820:TCF Transcription Factors; C544895:Tcf7l2 protein, mouse; D015534:Trans-Activators; D058118:Transcription Factor 7-Like 2 Protein; D014157:Transcription Factors; D051153:Wnt Proteins; C102068:Wnt10b protein, mouse; D029961:Zebrafish Proteins; D051176:beta Catenin