Elevated Fra-1 expression causes severe lipodystrophy
| Autor: | Vice Mandic, Christine Zech, Frank Driessler, Matthias Megges, Julia Luther, Erwin F. Wagner, Jan Tuckermann, Georg Schett, Mario M. Zaiss, Cornelis F. Calkhoven, Anne Reichardt, Jean-Pierre David, Bettina Herbort, Andreas Hess |
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| Rok vydání: | 2011 |
| Předmět: |
CD36 Antigens
Chromatin Immunoprecipitation medicine.medical_specialty Lipodystrophy CD36 Blotting Western Mice Transgenic Biology Polymerase Chain Reaction Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Osteogenesis Internal medicine Adipocyte Enhancer binding CEBPA Adipocytes medicine Animals Immunoprecipitation Transcription factor Cells Cultured 030304 developmental biology 0303 health sciences Adipogenesis Osteoblasts Ccaat-enhancer-binding proteins Osteoblast Cell Biology Magnetic Resonance Imaging Mice Inbred C57BL medicine.anatomical_structure Endocrinology chemistry 030220 oncology & carcinogenesis CCAAT-Enhancer-Binding Proteins biology.protein Proto-Oncogene Proteins c-fos Protein Binding |
| Zdroj: | Journal of Cell Science Journal of Cell Science; Vol 124 |
| ISSN: | 1477-9137 0021-9533 |
| DOI: | 10.1242/jcs.079855 |
| Popis: | A shift from osteoblastogenesis to adipogenesis is one of the underlying mechanisms of decreased bone mass and increased fat during aging. We now uncover a new role for the transcription factor Fra-1 in suppressing adipogenesis. Indeed, Fra1 (Fosl1) transgenic (Fra1tg) mice, which developed progressive osteosclerosis as a result of accelerated osteoblast differentiation, also developed a severe general lipodystrophy. The residual fat of these mice appeared immature and expressed lower levels of adipogenic markers, including the fatty acid transporter Cd36 and the CCAAT/enhancer binding protein Cebpa. Consequently accumulation of triglycerides and free fatty acids were detected in the serum of fasting Fra1tg mice. Fra-1 acts cell autonomously because the adipogenic differentiation of Fra1 transgenic primary osteoblasts was drastically reduced, and overexpression of Fra-1 in an adipogenic cell line blocked their differentiation into adipocytes. Strikingly, Cebpa was downregulated in the Fra-1-overexpressing cells and Fra-1 could bind to the Cebpa promoter and directly suppress its activity. Thus, our data add to the known common systemic control of fat and bone mass, a new cell-autonomous level of control of cell fate decision by which the osteogenic transcription factor Fra-1 opposes adipocyte differentiation by inhibiting C/EBPα. |
| Databáze: | OpenAIRE |
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