Peroxisome-proliferator-activated receptor γ suppresses Wnt/β-catenin signalling during adipogenesis
- 15 December 2003
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 376 (3), 607-613
- https://doi.org/10.1042/bj20030426
Abstract
The Wnt/β-catenin signalling pathway appears to operate to maintain the undifferentiated state of preadipocytes by inhibiting adipogenic gene expression. To define the mechanisms regulating suppression of Wnt/β-catenin signalling, we analysed the β-catenin expression in response to activation of transcription factors that regulate adipogenesis. The results show an extensive down-regulation of nuclear β-catenin that occurs during the first few days of differentiation of 3T3-L1 preadipocytes and coincides with the induction of the adipogenic transcription factors, C/EBPβ (CCAAT-enhancer-binding protein) and PPARγ (peroxisome-proliferator-activated receptor). To assess the role of each of these factors in this process, we conditionally overexpressed C/EBPβ in Swiss mouse fibroblasts using the TET-off system. Abundant expression of C/EBPβ alone had minimal effect on β-catenin expression, whereas expression of C/EBPβ, in the presence of dexamethasone, induced PPARγ expression and caused a measurable decrease in β-catenin. In addition, exposure of cells expressing both C/EBPβ and PPARγ to a potent PPARγ ligand resulted in an even greater decrease in β-catenin by mechanisms that involve the proteasome. Our studies also suggest a reciprocal relationship between PPARγ activity and β-catenin expression, since ectopic production of Wnt-1 in preadipocytes blocked the induction of PPARγ gene expression. Moreover, by suppressing β-catenin expression, ectopic expression of PPARγ in Wnt-1-expressing preadipocytes rescued the block in adipogenesis after their exposure to the PPARγ ligand, troglitazone.Keywords
This publication has 39 references indexed in Scilit:
- APC-dependent suppression of colon carcinogenesis by PPARγProceedings of the National Academy of Sciences of the United States of America, 2002
- Octanoate Attenuates Adipogenesis in 3T3-L1 PreadipocytesJournal of Nutrition, 2002
- T0070907, a Selective Ligand for Peroxisome Proliferator-activated Receptor γ, Functions as an Antagonist of Biochemical and Cellular ActivitiesJournal of Biological Chemistry, 2002
- Conditional ectopic expression of C/EBP beta in NIH-3T3 cells induces PPAR gamma and stimulates adipogenesis.Genes & Development, 1995
- Cascade regulation of terminal adipocyte differentiation by three members of the C/EBP family of leucine zipper proteins.Genes & Development, 1995
- Stimulation of adipogenesis in fibroblasts by PPARγ2, a lipid-activated transcription factorCell, 1994
- Production of high-titer helper-free retroviruses by transient transfection.Proceedings of the National Academy of Sciences of the United States of America, 1993
- Reciprocal Regulation of Adipogenesis by Myc and C/EBPαScience, 1992
- Regulated expression of three C/EBP isoforms during adipose conversion of 3T3-L1 cells.Genes & Development, 1991
- An established preadipose cell line and its differentiation in culture II. Factors affecting the adipose conversionCell, 1975