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On the Role of FOX Transcription Factors in Adipocyte Differentiation and Insulin-stimulated Glucose Uptake*S⃞

By Isabelle Gerin, Guido T. Bommer, Martin E. Lidell, Anna Cederberg, Sven Enerback and Ormond A. MacDougald


In this study, we explore the effects of several FOX and mutant FOX transcription factors on adipocyte determination, differentiation, and metabolism. In addition to Foxc2 and Foxo1, we report that Foxf2, Foxp1, and Foxa1 are other members of the Fox family that show regulated expression during adipogenesis. Although enforced expression of FOXC2 inhibits adipogenesis, Foxf2 slightly enhances the rate of differentiation. Constitutively active FOXC2-VP16 inhibits adipogenesis through multiple mechanisms. FOXC2-VP16 impairs the transient induction of C/EBPβ during adipogenesis and induces expression of the transcriptional repressor Hey1 as well as the activator of Wnt/β-catenin signaling, Wnt10b. The constitutive transcriptional repressor, FOXC2-Eng, enhances adipogenesis of preadipocytes and multipotent mesenchymal precursors and determines NIH-3T3 and C2C12 cells to the adipocyte lineage. Although PPARγ ligand or C/EBPα are not necessary for stimulation of adipogenesis by FOXC2-Eng, at least low levels of PPARγ protein are absolutely required. Finally, expression of FOXC2-Eng in adipocytes increases insulin-stimulated glucose uptake, further expanding the profound and pleiotropic effects of FOX transcription factors on adipocyte biology

Topics: Molecular Basis of Cell and Developmental Biology
Publisher: American Society for Biochemistry and Molecular Biology
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Provided by: PubMed Central
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