Fra-2/AP-1 controls adipocyte differentiation and survival by regulating PPAR? and hypoxia

Luther J, Ubieta Hernández K, Hannemann N, Jimenez M, Garcia-Cuellar MP, Zech C, Schett G, Wagner EF, Bozec A (2014)

Publication Type: Journal article

Publication year: 2014

Journal

Cell Death and Differentiation Nature Publishing Group: Open Access Hybrid Model Option B

Book Volume: 21

Pages Range: 655-64

Journal Issue: 4

DOI: 10.1038/cdd.2013.198

Abstract

Adipocyte cell number is a crucial factor for controlling of body weight and metabolic function. The regulation of adipocyte numbers in the adult organism is not fully understood but is considered to depend on the homeostasis of cell differentiation and apoptosis. Herein, we show that targeted deletion of the activator protein (AP-1)-related transcription factor Fra-2 in adipocytes in vivo (Fra-2(?adip) mice) induces a high-turnover phenotype with increased differentiation and apoptosis of adipocytes, leading to a decrease in body weight and fat pad mass. Importantly, adipocyte cell numbers were significantly reduced in Fra-2(?adip) mice. At the molecular level, Fra-2 directly binds to the PPAR?2 promoter and represses PPAR?2 expression. Deletion of Fra-2 leads to increased PPAR?2 expression and adipocyte differentiation as well as increased adipocyte apoptosis through upregulation of hypoxia-inducible factors (HIFs). These findings suggest that Fra-2 is an important checkpoint to control adipocyte turnover. Therefore, inhibition of Fra-2 may emerge as a useful strategy to increase adipocyte turnover and to reduce adipocyte numbers and fat mass in the body.

Authors with CRIS profile

Julia Luther Lehrstuhl für Genetik Kenia Ubieta Hernández Lehrstuhl für Genetik Nicole Hannemann Medizinische Fakultät Maria-Paz Garcia-Cuellar Lehrstuhl für Genetik Georg Schett Lehrstuhl für Innere Medizin III Aline Bozec Juniorprofessur für Osteoimmunologie

Involved external institutions

Spanish National Cancer Research Centre / Centro Nacional de Investigaciones Oncológicas (CNIO) ES Spain (ES)

How to cite

APA:

Luther, J., Ubieta Hernández, K., Hannemann, N., Jimenez, M., Garcia-Cuellar, M.-P., Zech, C.,... Bozec, A. (2014). Fra-2/AP-1 controls adipocyte differentiation and survival by regulating PPAR? and hypoxia. Cell Death and Differentiation, 21(4), 655-64. https://dx.doi.org/10.1038/cdd.2013.198

MLA:

Luther, Julia, et al. "Fra-2/AP-1 controls adipocyte differentiation and survival by regulating PPAR? and hypoxia." Cell Death and Differentiation 21.4 (2014): 655-64.

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