Genistein inhibits CCAAT/enhancer-binding protein beta (C/EBPbeta) activity and 3T3-L1 adipogenesis by increasing C/EBP homologous protein expression.
The tyrosine kinase inhibitor genistein inhibits 3T3-L1 adipogenesis when present during the first 72 h of differentiation. In this report, we investigated the underlying mechanisms involved in the anti-adipogenic effects of genistein. We found that genistein blocked the DNA binding and transcriptional activity of CCAAT/enhancer-binding protein beta (C/EBPbeta) during differentiation by promoting the expression of C/EBP homologous protein, a dominant-negative member of the C/EBP family. Loss of C/EBPbeta activity was manifested as a loss of differentiation-induced C/EBPalpha and peroxisome-proliferator-activated receptor gamma protein expression and a dramatic reduction in lipid accumulation. Further, we documented for the first time that C/EBPbeta was tyrosine-phosphorylated in vivo during differentiation and in vitro by activated epidermal growth factor receptor. Genistein inhibited both of these events. Collectively, these results indicate that genistein blocks adipogenesis and C/EBPbeta activity by increasing the level of C/EBP homologous protein and possibly by inhibiting the tyrosine phosphorylation of C/EBPbeta.
Harmon
Anne W
AW
Department of Nutrition, CB# 7461 McGavran-Greenberg Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
Patel
Yashomati M
YM
Harp
Joyce B
JB
D016475:3T3 Cells; D017667:Adipocytes / Q000166:cytology* / Q000378:metabolism; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D001391:Azo Compounds / Q000494:pharmacology; D022782:CCAAT-Enhancer-Binding Protein-beta / Q000037:antagonists & inhibitors*; D002454:Cell Differentiation; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D004396:Coloring Agents / Q000494:pharmacology; D004247:DNA / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology*; D015151:Immunoblotting; D007529:Isoflavones / Q000494:pharmacology; D050356:Lipid Metabolism; D051379:Mice; D010766:Phosphorylation; D011233:Precipitin Tests; D011485:Protein Binding; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism; D013997:Time Factors; D014157:Transcription Factors / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D014443:Tyrosine / Q000378:metabolism
D016588:Anticarcinogenic Agents; D001391:Azo Compounds; D022782:CCAAT-Enhancer-Binding Protein-beta; D004396:Coloring Agents; D004791:Enzyme Inhibitors; D007529:Isoflavones; D018160:Receptors, Cytoplasmic and Nuclear; D014157:Transcription Factors; D014443:Tyrosine; C004742:daidzein; D004247:DNA; D019833:Genistein; C011049:oil red O