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.
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