Avian uncoupling protein (avUCP) is orthologous to UCP3, which is suggested to be involved in fatty acid metabolism and to limit the mitochondrial production of reactive oxygen species in mammals. In the chicken, the role and regulation of avUCP remain to be clarified. The aim of this study was to explore the control of avUCP expression by the beta-adrenergic system, known to be involved in avian thermoregulation and lipid utilization, and in UCP expression in mammals. Therefore, we measured the expression of avUCP mRNA and protein in the Pectoralis major muscle of chickens injected with the beta(2) agonist isoproterenol, and we investigated the potential pathways involved in the regulation of avUCP mRNA expression. Avian UCP mRNA expression was increased 7-fold 4 h after isoproterenol injection, leading to a tendency to a 40% increase in avUCP protein 24 h post-injection. This increase was preceded, 30 min after isoproterenol injection, by changes in the chicken thyroid status and in the muscular expression of PPAR alpha, PPAR beta/delta, and PPAR gamma coactivator-1 alpha (PGC-1 alpha). Moreover, the analysis of the avUCP promoter sequence suggested potential binding sites for PPARs and for thyroid hormone receptors. We also detected the activation of AMP-activated protein kinase, which has recently been reported to be involved in UCP3 regulation in mammals. This study presents for the first time evidence of beta-adrenergic control on avUCP messenger expression in chicken muscle and suggests the potential involvement of AMPK and several transcription factors in this regulation. (C) 2010 Elsevier Inc. All rights reserved.