| 20179324 |
Gustafson B, Smith U: Activation of canonical Wingless-type MMTV integration site family (WNT) signaling in mature adipocytes increases &-{beta}catenin levels and leads to cell dedifferentiation and insulin resistance. J Biol Chem. 2010 Feb 23.
Canonical Wnt ligands are secreted by several cell types in the adipose tissue. We examined if also mature adipocytes can be target cells and found that canonical Wnt activation by Wnt3a induced a marked dedifferentiation of both 3T3-L1 and human adipocytes. Typical adipogenic markers were reduced while undifferentiated cell markers like Pref-1, Wnt10b and GATA2 were increased. The cells also became insulin resistant with impaired upstream insulin signaling and reduced glucose uptake. Wnt3a stabilised beta-catenin in the absence of the LRP6 receptor and with maintained axin and Dickkopf-1 protein expression. PPARgamma was repressed and PPARgamma ligands could not restore the adipogenic markers or reduce the gamma-catenin levels. The dedifferentiated adipocytes expressed the myofibroblast marker alpha-SMA and were also susceptible to osteogenic transdifferentiation. These results identify a novel pathway in mature adipose cells which is critical for maintaining the normal adipocyte phenotype and insulin sensitivity. |
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