1. Retinoic Acid Blocks Adipogenesis by Inhibiting C/EBPβ-Mediated Transcription
- Author
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Samuel L. Krakow, E J Schwarz, Dalei Shao, Mitchell A. Lazar, and Mauricio J. Reginato
- Subjects
Transcriptional Activation ,medicine.medical_specialty ,Transcription, Genetic ,Receptors, Retinoic Acid ,Recombinant Fusion Proteins ,Cellular differentiation ,Retinoic acid ,Receptors, Cytoplasmic and Nuclear ,Tretinoin ,Biology ,Ligands ,Transfection ,digestive system ,Mice ,chemistry.chemical_compound ,Internal medicine ,Adipocytes ,medicine ,Animals ,Molecular Biology ,Transcription factor ,Regulation of gene expression ,Ccaat-enhancer-binding proteins ,digestive, oral, and skin physiology ,Nuclear Proteins ,Cell Differentiation ,3T3 Cells ,Cell Biology ,Cell biology ,DNA-Binding Proteins ,Endocrinology ,Gene Expression Regulation ,chemistry ,Adipogenesis ,CCAAT-Enhancer-Binding Proteins ,Ectopic expression ,biological phenomena, cell phenomena, and immunity ,hormones, hormone substitutes, and hormone antagonists ,Transcription Factors ,Research Article ,medicine.drug - Abstract
Adipocyte differentiation is thought to involve sequential induction of the transcription factors C/EBPbeta, peroxisome proliferator-activated receptor gamma (PPARgamma), and C/EBPalpha. C/EBPalpha expression is both necessary and sufficient for adipocyte differentiation. Here we report that ectopic expression of either C/EBPalpha or C/EBPbeta induces PPARgamma expression and adipogenesis and that retinoic acid (RA) completely inhibits adipogenesis by either form of C/EBP. In studies of normal preadipocytes, RA does not prevent C/EBPbeta induction but blocks induction of PPARgamma, C/EBPalpha, and adipogenesis. In transient transfection studies, liganded RA receptor (RAR) specifically blocks transcriptional activation by either C/EBPalpha or C/EBPbeta. These results strongly suggest that C/EBPalpha substitutes for C/EBPbeta to induce adipocyte differentiation and that liganded RAR inhibits adipogenesis by blocking C/EBPbeta-mediated induction of downstream genes.
- Published
- 1997