Biochemical and Biophysical Research Communications
Wnt/Lrp/β-catenin signaling suppresses adipogenesis by inhibiting mutual activation of PPARγ and C/EBPα
Section snippets
Materials and methods
Materials. 3T3-L1 cells were purchased from Human Science Research Resources Bank (Osaka, Japan). Insulin and 3-isobutyl-2-methylxanthine were purchased from Wako Pure Chemical Industries Ltd. (Osaka, Japan). Dexamethasone was purchased from ICN Biomedicals, Inc. (Aurora, OH). Troglitazone and anti-β-actin antibody were purchased from Sigma (St. Louis, MO). Anti-PPARγ, anti-C/EBPα, anti-C/EBPβ, and anti-C/EBPδ antibodies were obtained from Santa Cruz Biotechnology, Inc. (Santa Cruz, CA).
Wnt3a suppresses C/EBPβ- and C/EBPδ-induced adipogenesis
To investigate the role of Wnt/β-catenin signaling in adipogenesis, we used 3T3-L1 cells. Wnt3a stabilized β-catenin in cytosol, which was subsequently translocated into the nucleus (data not shown). Luciferase reporter assay also revealed that Wnt3a activates TCF-mediated transcription (data not shown). Next, we treated 3T3-L1 cells with 2-day MDI in the presence or absence of Wnt3a. As shown previously [4], [13], Wnt3a inhibits MDI-induced adipogenesis. Wnt3a did not affect the induction of
Discussion
Recently, many investigators have focused on the mechanisms by which Wnt/β-catenin signaling inhibits adipogenesis [4], [22]. Consistent with previous data [4], [13], Wnt/β-catenin signaling suppressed the induction of PPARγ and C/EBPα without affecting C/EBPβ and C/EBPδ during MDI-induced adipogenesis of 3T3-L1 cells. As these findings suggest, suppression of C/EBPβ/δ-induced PPARγ expression is a possible underlying mechanism. We therefore examined the relationship between C/EBPβ/δ and PPARγ.
Acknowledgments
We thank Dr. R. Nishimura (Osaka University Graduate School of Dentistry) for useful advice and Dr. M. Makishima for the PPARγ2 expression vector.
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