Chibby promotes adipocyte differentiation through inhibition of beta-catenin signaling.
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.
Li
Feng-Qian
FQ
SUNY at Stony Brook, Department of Pharmacology, Stony Brook, NY 11794-8651, USA.
Singh
Amar M
AM
Mofunanya
Adaobi
A
Love
Damon
D
Terada
Naohiro
N
Moon
Randall T
RT
Takemaru
Ken-Ichi
K
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000502:physiology*; D050156:Adipogenesis; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002454:Cell Differentiation; D002460:Cell Line; D002478:Cells, Cultured; D053595:Embryonic Stem Cells / Q000166:cytology / Q000502:physiology; D017930:Genes, Reporter; D006651:Histocytochemistry; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D051379:Mice; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference; D015398:Signal Transduction; D051176:beta Catenin / Q000037:antagonists & inhibitors*
C473750:CBY1 protein, human; D002352:Carrier Proteins; C517894:Chibby protein, mouse; D009687:Nuclear Proteins; D051176:beta Catenin; D008156:Luciferases