Chibby promotes adipocyte differentiation through inhibition of beta-catenin signaling

Mol Cell Biol. 2007 Jun;27(12):4347-54. doi: 10.1128/MCB.01640-06. Epub 2007 Apr 2.

Abstract

The canonical Wnt/beta-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 beta-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 beta-catenin, since gain or loss of function of Cby influences beta-catenin signaling in 3T3-L1 cells. Our results therefore establish Cby as a novel proadipogenic factor required for adipocyte differentiation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3-L1 Cells
  • Adipocytes / physiology*
  • Adipogenesis
  • Animals
  • Carrier Proteins / genetics
  • Carrier Proteins / physiology*
  • Cell Differentiation*
  • Cell Line
  • Cells, Cultured
  • Embryonic Stem Cells / cytology
  • Embryonic Stem Cells / physiology
  • Genes, Reporter
  • Histocytochemistry
  • Humans
  • Luciferases / metabolism
  • Mice
  • Nuclear Proteins / genetics
  • Nuclear Proteins / physiology*
  • RNA Interference
  • Signal Transduction
  • beta Catenin / antagonists & inhibitors*

Substances

  • CBY1 protein, human
  • Carrier Proteins
  • Chibby protein, mouse
  • Nuclear Proteins
  • beta Catenin
  • Luciferases