Regulation of Wnt signaling during adipogenesis

Christina N. Bennett, Sarah E. Ross, Kenneth A. Longo, Laszlo Bajnok, Nahid Hemati, Kirk W. Johnson, Stephen D. Harrison, Ormond A. MacDougald

Research output: Contribution to journalArticle

500 Citations (Scopus)

Abstract

We have identified Wnt10b as a potent inhibitor of adipogenesis that must be suppressed for preadipocytes to differentiate in vitro. Here, we demonstrate that a specific inhibitor of glycogen synthase kinase 3, CHIR 99021, mimics Wnt signaling in preadipocytes. CHIR 99021 stabilizes free cytosolic β-catenin and inhibits adipogenesis by blocking induction of CCAAT/enhancer-binding protein α and peroxisome proliferatoractivated receptor γ. Preadipocyte differentiation is inhibited when 3T3-L1 cells are exposed to CHIR 99021 for any 24 h period during the first 3 days of adipogenesis. Consistent with this time frame of inhibition, expression of Wnt10b mRNA is suppressed upon induction of differentiation, with a 50% decline by 6 h and complete inhibition by 36 h. Of the agents used to induce differentiation, exposure of 3T3-L1 cells to methyl-isobutylxanthine or cAMP is sufficient to suppress expression of Wnt10b mRNA. Inhibition of adipogenesis by Wnt10b is likely mediated by Wnt receptors, Frizzled 1, 2, and/or 5, and co-receptors low density lipoprotein receptor-related proteins 5 and 6. These receptors, like Wnt10b, are highly expressed in preadipocytes and stromal vascular cells. Finally, we demonstrate that disruption of extracellular Wnt signaling by expression of secreted Frizzled related proteins causes spontaneous adipocyte conversion.

Original languageEnglish
Pages (from-to)30998-31004
Number of pages7
JournalJournal of Biological Chemistry
Volume277
Issue number34
DOIs
Publication statusPublished - Aug 23 2002

    Fingerprint

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Bennett, C. N., Ross, S. E., Longo, K. A., Bajnok, L., Hemati, N., Johnson, K. W., Harrison, S. D., & MacDougald, O. A. (2002). Regulation of Wnt signaling during adipogenesis. Journal of Biological Chemistry, 277(34), 30998-31004. https://doi.org/10.1074/jbc.M204527200