Pref-1 (pre-adipocyte factor-1) is known to play a central role in regulating white adipocyte differentiation, but the role of Pref-1 in BAT (brown adipose tissue) has not been analysed. In the present study we found that Pref-1 expression is high in fetal BAT and declines progressively after birth. However, Pref-1-null mice showed unaltered fetal development of BAT, but exhibited signs of over-activation of BAT thermogenesis in the post-natal period. In C/EBP (CCAAT/enhancer-binding protein) α-null mice, a rodent model of impaired fetal BAT differentiation, Pref-1 was dramatically overexpressed, in association with reduced expression of the Ucp1 (uncoupling protein 1) gene, a BAT-specific marker of thermogenic differentiation. In brown adipocyte cell culture models, Pref-1 was mostly expressed in pre-adipocytes and declined with brown adipocyte differentiation. The transcription factor C/EBPδ activated the Pref-1 gene transcription in brown adipocytes, through binding to the proximal promoter region. Accordingly, siRNA (small interfering RNA)-induced C/EBPδ knockdown led to reduced Pref-1 gene expression. This effect is consistent with the observed overexpression of C/EBPδ in C/EBPα-null BAT and high expression of C/EBPδ in brown pre-adipocytes. Dexamethasone treatment of brown pre-adipocytes suppressed Pref-1 down-regulation occurring throughout the brown adipocyte differentiation process, increased the expression of C/EBPδ and strongly impaired expression of the thermogenic markers UCP1 and PGC-1α [PPARγ (peroxisome-proliferator-activated receptor γ) co-activator-α]. However, it did not alter normal fat accumulation or expression of non-BAT-specific genes. Collectively, these results specifically implicate Pref-1 in controlling the thermogenic gene expression program in BAT, and identify C/EBPδ as a novel transcriptional regulator of Pref-1 gene expression that may be related to the specific role of glucocorticoids in BAT differentiation.
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Research Article|
April 16 2012
Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBPδ
Jordi Armengol;
Jordi Armengol
*Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), 08028 Barcelona, Spain
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Josep A. Villena;
Josep A. Villena
†Laboratory of Metabolism and Obesity, Unit of Diabetes and Metabolism, Institut de Recerca Vall d'Hebron, 08035 Barcelona, Spain
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Elayne Hondares;
Elayne Hondares
*Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), 08028 Barcelona, Spain
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María C. Carmona;
María C. Carmona
*Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), 08028 Barcelona, Spain
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Hei Sook Sul;
Hei Sook Sul
‡Department of Nutritional Science and Toxicology, University of California, Berkeley, Berkeley, CA 94720, U.S.A.
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Roser Iglesias;
Roser Iglesias
*Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), 08028 Barcelona, Spain
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Marta Giralt;
Marta Giralt
*Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), 08028 Barcelona, Spain
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Francesc Villarroya
Francesc Villarroya
1
*Departament de Bioquímica i Biologia Molecular, Institut de Biomedicina de la Universitat de Barcelona (IBUB) and CIBER Fisiopatologia de la Obesidad y Nutrición (CIBEROBN), 08028 Barcelona, Spain
1To whom correspondence should be addressed (email [email protected]).
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Publisher: Portland Press Ltd
Received:
September 26 2011
Revision Received:
January 25 2012
Accepted:
February 13 2012
Accepted Manuscript online:
February 13 2012
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2012 Biochemical Society
2012
Biochem J (2012) 443 (3): 799–810.
Article history
Received:
September 26 2011
Revision Received:
January 25 2012
Accepted:
February 13 2012
Accepted Manuscript online:
February 13 2012
Connected Content
This is a commentary on:
Pref-1 preferentially inhibits heat production in brown adipose tissue
Citation
Jordi Armengol, Josep A. Villena, Elayne Hondares, María C. Carmona, Hei Sook Sul, Roser Iglesias, Marta Giralt, Francesc Villarroya; Pref-1 in brown adipose tissue: specific involvement in brown adipocyte differentiation and regulatory role of C/EBPδ. Biochem J 1 May 2012; 443 (3): 799–810. doi: https://doi.org/10.1042/BJ20111714
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