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On the role of FOX transcription factors in adipocyte differentiation and insulin-stimulated glucose uptake.

Journal article
Authors Isabelle Gerin
Guido T Bommer
Martin Lidell
Anna Cederberg
Sven Enerbäck
Ormond A Macdougald
Published in The Journal of biological chemistry
Volume 284
Issue 16
Pages 10755-63
ISSN 0021-9258
Publication year 2009
Published at Institute of Biomedicine, Department of Medical and Clinical Genetics
Pages 10755-63
Language en
Links dx.doi.org/10.1074/jbc.M809115200
Keywords 3T3-L1 Cells, Adipocytes, cytology, physiology, Adipogenesis, physiology, Animals, Cell Cycle Proteins, genetics, metabolism, Cell Differentiation, physiology, Forkhead Transcription Factors, genetics, metabolism, Gene Expression Regulation, Glucose, metabolism, Humans, Insulin, metabolism, Mice, PPAR gamma, antagonists & inhibitors, genetics, metabolism, Protein Isoforms, genetics, metabolism, Recombinant Fusion Proteins, genetics, metabolism
Subject categories Medical and Health Sciences

Abstract

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/EBPbeta during adipogenesis and induces expression of the transcriptional repressor Hey1 as well as the activator of Wnt/beta-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 PPARgamma ligand or C/EBPalpha are not necessary for stimulation of adipogenesis by FOXC2-Eng, at least low levels of PPARgamma 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.

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