RESUMO
In rodent brown adipose tissue, the beta-adrenergic signaling is believed, by an action on PGC-1alpha, to control UCP1 expression and mitochondriogenesis. We addressed this hypothesis using beta(1)/beta(2)/beta(3)-adrenoceptor knockout (beta-less) brown adipocytes in primary culture. In these cells: (a) proliferation and differentiation into multilocular cells were normal; (b) UCP1 mRNA expression was dramatically decreased (by 93%), whereas PGC-1alpha and mtTFA mRNA expressions were not; (c) UCP1, PGC-1alpha and COX IV protein expressions were decreased by 97%, 62% and 22%, respectively. Altogether the data show a dissociation between the control of UCP1, which is mostly beta-adrenoceptor-dependent and that of PGC-1alpha and of mitochondriogenesis which are not.
Assuntos
Adipócitos/fisiologia , Tecido Adiposo Marrom/fisiologia , Proteínas de Transporte/fisiologia , Proteínas de Membrana/fisiologia , Receptores Adrenérgicos beta/fisiologia , Transativadores/fisiologia , Adipócitos/citologia , Tecido Adiposo Marrom/citologia , Animais , Sequência de Bases , Western Blotting , Proteínas de Transporte/genética , Primers do DNA , Canais Iônicos , Proteínas de Membrana/genética , Camundongos , Proteínas Mitocondriais , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo , Reação em Cadeia da Polimerase , RNA Mensageiro/genética , Receptores Adrenérgicos beta/genética , Fatores de Transcrição , Proteína Desacopladora 1RESUMO
Knockout of the translation inhibitor 4E-BP1 induces an overexpression of uncoupling protein-1 (UCP1) [Nature Medicine 7 (2001) 1128]. A possible inverse control of UCP1 and 4E-BP1 expressions in mouse brown adipose tissue was investigated. Cold-exposure, which increases the expression of UCP1, decreased that of 4E-BP1 mRNA in wild type but not in beta1/beta2/beta3-adrenoceptor knockout mice. Administration of the beta3-adrenoceptor agonist CL 316246 decreased 4E-BP1 mRNA by 75% and protein by 41% after 6 and 48 h, respectively. Our data are the first report of a regulation by the beta3-adrenoceptor of 4E-BP1 expression. They support a role of the latter in adaptive thermogenesis.