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Chibby Promotes Adipocyte Differentiation through Inhibition of ß-Catenin Signaling

Department of Pharmacology,¹ Graduate Program in Genetics,² Graduate Program in Molecular and Cellular Pharmacology, SUNY at Stony Brook, Stony Brook, New York 11794,³ Department of Pathology, University of Florida, Gainesville, Florida 32610,⁴ Department of Pharmacology, HHMI, Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, Washington 98195⁵

Received 1 September 2006/ Returned for modification 16 October 2006/ Accepted 24 March 2007

The canonical Wnt/ß-catenin signaling pathway plays diverse roles in embryonic development and disease. Activation of this pathway, likely by Wnt-10b, has been shown to inhibit adipogenesis in cultured 3T3-L1 preadipocytes and in mice. Here, we report that the ß-catenin antagonist Chibby (Cby) is required for adipocyte differentiation. Cby is expressed in adipose tissue in mice, and Cby protein levels increase during adipogenic differentiation of 3T3-L1 cells. Ectopic expression of Cby induces spontaneous differentiation of these cells into mature adipocytes to an extent similar to that of dominant-negative Tcf-4. In contrast, depletion of Cby by RNA interference potently blocks adipogenesis of 3T3-L1 and mouse embryonic stem cells. In support of this, embryonic fibroblasts obtained from Cby-deficient embryos display attenuated differentiation to the adipogenic lineage. Mechanistically, Cby promotes adipocyte differentiation, in part by inhibiting ß-catenin, since gain or loss of function of Cby influences ß-catenin signaling in 3T3-L1 cells. Our results therefore establish Cby as a novel proadipogenic factor required for adipocyte differentiation.

Published ahead of print on 2 April 2007.

This article has been cited by other articles:

• Li, F.-Q., Mofunanya, A., Harris, K., Takemaru, K.-I. (2008). Chibby cooperates with 14-3-3 to regulate {beta}-catenin subcellular distribution and signaling activity. J. Cell Biol. 181: 1141-1154 [Abstract] [Full Text]