C/EBPβ (CCAAT/enhancer-binding protein β) is a transcriptional regulator of the UCP1 (uncoupling protein-1) gene, the specific marker gene of brown adipocytes that is responsible for their thermogenic capacity. To investigate the role of C/EBPβ in brown fat, we studied the C/EBPβ-null mice. When placed in the cold, C/EBPβ−/− mice did not maintain body temperature. This cold-sensitive phenotype occurred, although UCP1 and PGC-1α (peroxisome-proliferator-activated receptor γ co-activator-1α) gene expression was unaltered in brown fat of C/EBPβ−/− mice. The UCP1 gene promoter was repressed by the truncated inhibitory C/EBPβ isoform LIP (liver-enriched transcriptional inhibitory protein, the truncated inhibitory C/EBPβ isoform). Since C/EBPβ-null mice lack both C/EBPβ isoforms, active LAP (liver-enriched transcriptional activatory protein, the active C/EBPβ isoform) and LIP, the absence of LIP may have a stronger effect than the absence of LAP upon UCP1 gene expression. Gene expression for UCP2 and UCP3 was not impaired in all tissues analysed. In primary brown adipocytes from C/EBPβ−/− mice, induction of gene expression by noradrenaline was preserved. In contrast, the expression of genes related to lipid storage was impaired, as was the amount of triacylglycerol mobilized after acute cold exposure in brown fat from C/EBPβ−/− mice. LPL (lipoprotein lipase) activity was also impaired in brown fat, but not in other tissues of C/EBPβ−/− mice. LPL protein levels were also diminished, but this effect was independent of changes in LPL mRNA, suggesting that C/EBPβ is involved in the post-transcriptional regulation of LPL gene expression in brown fat. In summary, defective thermoregulation owing to the lack of C/EBPβ is associated with the reduced capacity to supply fatty acids as fuels to sustain brown fat thermogenesis.
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Research Article|
June 21 2005
Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBPβ
M. Carmen CARMONA;
M. Carmen CARMONA
*Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028-Barcelona, Catalunya, Spain
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Elayne HONDARES;
Elayne HONDARES
*Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028-Barcelona, Catalunya, Spain
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M. Luisa RODRÍGUEZ DE LA CONCEPCIÓN;
M. Luisa RODRÍGUEZ DE LA CONCEPCIÓN
*Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028-Barcelona, Catalunya, Spain
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Víctor RODRÍGUEZ-SUREDA;
Víctor RODRÍGUEZ-SUREDA
*Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028-Barcelona, Catalunya, Spain
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Julia PEINADO-ONSURBE;
Julia PEINADO-ONSURBE
*Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028-Barcelona, Catalunya, Spain
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Valeria POLI;
Valeria POLI
†Dipartimento di Genetica, Biologia e Biochimica, Universitá di Torino, 10126-Torino, Italy
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Roser IGLESIAS;
Roser IGLESIAS
*Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028-Barcelona, Catalunya, Spain
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Francesc VILLARROYA;
Francesc VILLARROYA
*Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028-Barcelona, Catalunya, Spain
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Marta GIRALT
Marta GIRALT
1
*Departament de Bioquímica i Biologia Molecular, Universitat de Barcelona, E-08028-Barcelona, Catalunya, Spain
1To whom correspondence should be addressed (email mgiralt@ub.edu).
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Publisher: Portland Press Ltd
Received:
January 04 2005
Revision Received:
March 01 2005
Accepted:
March 11 2005
Accepted Manuscript online:
March 11 2005
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London
2005
Biochem J (2005) 389 (1): 47–56.
Article history
Received:
January 04 2005
Revision Received:
March 01 2005
Accepted:
March 11 2005
Accepted Manuscript online:
March 11 2005
Citation
M. Carmen CARMONA, Elayne HONDARES, M. Luisa RODRÍGUEZ DE LA CONCEPCIÓN, Víctor RODRÍGUEZ-SUREDA, Julia PEINADO-ONSURBE, Valeria POLI, Roser IGLESIAS, Francesc VILLARROYA, Marta GIRALT; Defective thermoregulation, impaired lipid metabolism, but preserved adrenergic induction of gene expression in brown fat of mice lacking C/EBPβ. Biochem J 1 July 2005; 389 (1): 47–56. doi: https://doi.org/10.1042/BJ20050009
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