title: Regulation of the expression of the avian uncoupling protein 3 by isoproterenol and fatty acids in chick myoblasts: possible involvement of AMPK and PPARalpha?
abstract: 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 β-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)α, PPARβ/δ, and PPARγ coactivator-1α (PGC-1α). The aim of the present study was to elucidate the mechanisms involving AMPK and PPARα 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 PPARα agonist WY-14643 strongly increased UCP3 mRNA expression. This study highlights the control of UCP3 expression by the β-adrenergic system and FA in chick myoblasts and demonstrates that its expression is directly regulated by AMPK and by PPARα. Overexpression of avian UCP3 might modulate energy utilization or limit oxidative stress when mitochondrial metabolism of FA is triggered by catecholamines.
authors.affiliation: INRA, UR83 Recherches Avicoles, F-37380 Nouzilly, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Joubert
authors.forename: Sonia
authors.initials: S
authors.lastname: Métayer-Coustard
authors.forename: Sabine
authors.initials: S
authors.lastname: Crochet
authors.forename: Estelle
authors.initials: E
authors.lastname: Cailleau-Audouin
authors.forename: Joëlle
authors.initials: J
authors.lastname: Dupont
authors.forename: Michel Jacques
authors.initials: MJ
authors.lastname: Duclos
authors.forename: Sophie
authors.initials: S
authors.lastname: Tesseraud
authors.forename: Anne
authors.initials: A
authors.lastname: Collin
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D030161:Avian Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D002645:Chickens / Q000502:physiology*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D004734:Energy Metabolism / Q000502:physiology; D005227:Fatty Acids / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D024101:Mitochondrial Proteins / Q000378:metabolism*; D000071245:Mitochondrial Uncoupling Proteins; D023421:Models, Animal; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D018384:Oxidative Stress / Q000502:physiology; D047493:PPAR alpha / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction / Q000502:physiology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000318:Adrenergic beta-Agonists; D030161:Avian Proteins; D017362:Cyclic AMP Response Element-Binding Protein; D005227:Fatty Acids; D024101:Mitochondrial Proteins; D000071245:Mitochondrial Uncoupling Proteins; D047493:PPAR alpha; D012333:RNA, Messenger; C422907:mitochondrial uncoupling protein, chicken; D048051:p38 Mitogen-Activated Protein Kinases; D055372:AMP-Activated Protein Kinases; D007545:Isoproterenol