Research ExplorerPublicationsElevated Fra-1 expression causes severe lipodystrophy

Elevated Fra-1 expression causes severe lipodystrophy

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Elevated Fra-1 expression causes severe lipodystrophy. / Luther, Julia; Driessler, Frank; Megges, Matthias; Hess, Andreas; Herbort, Bettina; Mandic, Vice; Zaiss, Mario M; Reichardt, Anne; Zech, Christine; Tuckermann, Jan P; Calkhoven, Cornelis F; Wagner, Erwin F; Schett, Georg; David, Jean-Pierre.

In: J CELL SCI, Vol. 124, No. Pt 9, 01.05.2011, p. 1465-76.

Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review

Harvard

Luther, J, Driessler, F, Megges, M, Hess, A, Herbort, B, Mandic, V, Zaiss, MM, Reichardt, A, Zech, C, Tuckermann, JP, Calkhoven, CF, Wagner, EF, Schett, G & David, J-P 2011, 'Elevated Fra-1 expression causes severe lipodystrophy', J CELL SCI, vol. 124, no. Pt 9, pp. 1465-76. https://doi.org/10.1242/jcs.079855

APA

Luther, J., Driessler, F., Megges, M., Hess, A., Herbort, B., Mandic, V., Zaiss, M. M., Reichardt, A., Zech, C., Tuckermann, J. P., Calkhoven, C. F., Wagner, E. F., Schett, G., & David, J-P. (2011). Elevated Fra-1 expression causes severe lipodystrophy. J CELL SCI, 124(Pt 9), 1465-76. https://doi.org/10.1242/jcs.079855

Vancouver

Luther J, Driessler F, Megges M, Hess A, Herbort B, Mandic V et al. Elevated Fra-1 expression causes severe lipodystrophy. J CELL SCI. 2011 May 1;124(Pt 9):1465-76. https://doi.org/10.1242/jcs.079855

Bibtex

@article{fa3a1161913141c1955f322176e9c2b7,
title = "Elevated Fra-1 expression causes severe lipodystrophy",
abstract = "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.",
keywords = "Adipocytes, Adipogenesis, Animals, Antigens, CD36, Blotting, Western, CCAAT-Enhancer-Binding Proteins, Cells, Cultured, Chromatin Immunoprecipitation, Immunoprecipitation, Lipodystrophy, Magnetic Resonance Imaging, Mice, Mice, Inbred C57BL, Mice, Transgenic, Osteoblasts, Osteogenesis, Polymerase Chain Reaction, Protein Binding, Proto-Oncogene Proteins c-fos",
author = "Julia Luther and Frank Driessler and Matthias Megges and Andreas Hess and Bettina Herbort and Vice Mandic and Zaiss, {Mario M} and Anne Reichardt and Christine Zech and Tuckermann, {Jan P} and Calkhoven, {Cornelis F} and Wagner, {Erwin F} and Georg Schett and Jean-Pierre David",
year = "2011",
month = may,
day = "1",
doi = "10.1242/jcs.079855",
language = "English",
volume = "124",
pages = "1465--76",
journal = "J CELL SCI",
issn = "0021-9533",
publisher = "Company of Biologists Ltd",
number = "Pt 9",

}

RIS

TY - JOUR

T1 - Elevated Fra-1 expression causes severe lipodystrophy

AU - Luther, Julia

AU - Driessler, Frank

AU - Megges, Matthias

AU - Hess, Andreas

AU - Herbort, Bettina

AU - Mandic, Vice

AU - Zaiss, Mario M

AU - Reichardt, Anne

AU - Zech, Christine

AU - Tuckermann, Jan P

AU - Calkhoven, Cornelis F

AU - Wagner, Erwin F

AU - Schett, Georg

AU - David, Jean-Pierre

PY - 2011/5/1

Y1 - 2011/5/1

N2 - 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.

AB - 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.

KW - Adipocytes

KW - Adipogenesis

KW - Animals

KW - Antigens, CD36

KW - Blotting, Western

KW - CCAAT-Enhancer-Binding Proteins

KW - Cells, Cultured

KW - Chromatin Immunoprecipitation

KW - Immunoprecipitation

KW - Lipodystrophy

KW - Magnetic Resonance Imaging

KW - Mice

KW - Mice, Inbred C57BL

KW - Mice, Transgenic

KW - Osteoblasts

KW - Osteogenesis

KW - Polymerase Chain Reaction

KW - Protein Binding

KW - Proto-Oncogene Proteins c-fos

U2 - 10.1242/jcs.079855

DO - 10.1242/jcs.079855

M3 - SCORING: Journal article

C2 - 21486951

VL - 124

SP - 1465

EP - 1476

JO - J CELL SCI

JF - J CELL SCI

SN - 0021-9533

IS - Pt 9

ER -