The intracellular pathways and receptors mediating the effects of retinoic acid (RA) on the brown-fat-uncoupling-protein-1 gene (ucp-1) have been analysed. RA activates transcription of ucp-1 and the RA receptor (RAR) is known to be involved in this effect. However, co-transfection of an expression vector for retinoid-X receptor (RXR) increases the action of 9-cis RA but not the effects of all-trans RA on the ucp-1 promoter in brown adipocytes. Either RAR-specific {p-[(E)-2-(5,6,7,8,-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid} or RXR-specific [isopropyl-(E,E)-(R,S)-11-methoxy-3,7,11-trimethyldodeca-2,4-dienoate, or methoprene] synthetic compounds increase the expression of UCP-1 mRNA and the activity of chloramphenicol acetyltransferase expression vectors driven by the ucp-1 promoter. The RXR-mediated action of 9-cis RA requires the upstream enhancer region at -2469/-2318 in ucp-1. During brown-adipocyte differentiation RXRα and RXRγ mRNA expression is induced in parallel with UCP-1 mRNA, whereas the mRNA for the three RAR subtypes, α, β and γ, decreases. Co-transfection of murine expression vectors for the different RAR and RXR subtypes indicates that RARα and RARβ as well as RXRα are the major retinoid-receptor subtypes capable of mediating the responsiveness of ucp-1 to retinoids. It is concluded that the effects of retinoids on ucp-1 transcription involve both RAR- and RXR-dependent signalling pathways. The responsiveness of brown adipose tissue to retinoids in vivo relies on a complex combination of the capacity of RAR and RXR subtypes to mediate ucp-1 induction and their distinct expression in the differentiated brown adipocyte.
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January 2000
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Research Article|
December 17 1999
Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids
Rosa ALVAREZ
;
Rosa ALVAREZ
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028-Barcelona, Spain
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MaLuz CHECA
;
MaLuz CHECA
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028-Barcelona, Spain
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Sonia BRUN
;
Sonia BRUN
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028-Barcelona, Spain
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Octavi VI±AS
;
Octavi VI±AS
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028-Barcelona, Spain
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Teresa MAMPEL
;
Teresa MAMPEL
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028-Barcelona, Spain
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Roser IGLESIAS
;
Roser IGLESIAS
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028-Barcelona, Spain
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Marta GIRALT
;
Marta GIRALT
1Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Avda. Diagonal 645, 08028-Barcelona, Spain
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Francesc VILLARROYA
Francesc VILLARROYA
1
1To whom correspondence should be addressed (e-mail gombau@;porthos.bio.ub.es).
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Biochem J (2000) 345 (1): 91–97.
Article history
Received:
July 23 1999
Revision Received:
September 29 1999
Accepted:
October 22 1999
Citation
Rosa ALVAREZ, MaLuz CHECA, Sonia BRUN, Octavi VI±AS, Teresa MAMPEL, Roser IGLESIAS, Marta GIRALT, Francesc VILLARROYA; Both retinoic-acid-receptor- and retinoid-X-receptor-dependent signalling pathways mediate the induction of the brown-adipose-tissue-uncoupling-protein-1 gene by retinoids. Biochem J 1 January 2000; 345 (1): 91–97. doi: https://doi.org/10.1042/bj3450091
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