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              <p>Regulation of the expression of the avian uncoupling protein 3 by isoproterenol and fatty acids in chick myoblasts: possible involvement of AMPK and PPAR alpha? Am J Physiol Regul Integr Comp Physiol 301: R201-R208, 2011. First published April 20, 2011; doi:10.1152/ajpregu.00087.2010.-The avian uncoupling protein 3 (UCP3), mainly expressed in muscle tissue, could be involved in fatty acid (FA) metabolism, limitation of reactive oxygen species production, and/or nonshivering thermogenesis. We recently demonstrated that UCP3 mRNA expression was increased by isoproterenol (Iso), a beta-agonist, in chicken Pectoralis major. This upregulation was associated with changes in FA metabolism and variations in the activation of AMP-activated protein kinase (AMPK) and in the expression of the transcription factors peroxisome proliferator-activated receptor (PPAR)alpha, PPAR beta/delta, and PPAR gamma coactivator-1 alpha (PGC-1 alpha). The aim of the present study was to elucidate the mechanisms involving AMPK and PPAR alpha in UCP3 regulation in primary cultures of chick myoblasts. Avian UCP3 mRNA expression, associated with p38 mitogen-activated protein kinase (p38 MAPK) activation, was increased by Iso and/or FAs. The PKA pathway mediated the effects of Iso on UCP3 expression. FA stimulation also led to AMPK activation. Furthermore, the direct involvement of AMPK on UCP3 regulation was shown by using 5-aminoimidazole-4-carboxyamide ribonucleoside and Compound C. The use of the p38 MAPK inhibitor SB202190, which was associated with AMPK activation, also dramatically enhanced UCP3 mRNA expression. Finally the PPAR alpha agonist WY-14643 strongly increased UCP3 mRNA expression. This study highlights the control of UCP3 expression by the beta-adrenergic system and FA in chick myoblasts and demonstrates that its expression is directly regulated by AMPK and by PPAR alpha. Overexpression of avian UCP3 might modulate energy utilization or limit oxidative stress when mitochondrial metabolism of FA is triggered by catecholamines.</p>
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