Affiliation:
1. Department of Nutrition, CB# 7461 McGavran-Greenberg Hall, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, U.S.A.
Abstract
The tyrosine kinase inhibitor genistein inhibits 3T3-L1 adipogenesis when present during the first 72h 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 β (C/EBPβ) during differentiation by promoting the expression of C/EBP homologous protein, a dominant-negative member of the C/EBP family. Loss of C/EBPβ activity was manifested as a loss of differentiation-induced C/EBPα and peroxisome-proliferator-activated receptor γ protein expression and a dramatic reduction in lipid accumulation. Further, we documented for the first time that C/EBPβ 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/EBPβ activity by increasing the level of C/EBP homologous protein and possibly by inhibiting the tyrosine phosphorylation of C/EBPβ.
Subject
Cell Biology,Molecular Biology,Biochemistry
Cited by
92 articles.
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