title: 5'-AMP activated protein kinase α2 controls substrate metabolism during post-exercise recovery via regulation of pyruvate dehydrogenase kinase 4.
abstract: It is well known that exercise has a major impact on substrate metabolism for many hours after exercise. However, the regulatory mechanisms increasing lipid oxidation and facilitating glycogen resynthesis in the post-exercise period are unknown. To address this, substrate oxidation was measured after prolonged exercise and during the following 6 h post-exercise in 5´-AMP activated protein kinase (AMPK) α2 and α1 knock-out (KO) and wild-type (WT) mice with free access to food. Substrate oxidation was similar during exercise at the same relative intensity between genotypes. During post-exercise recovery, a lower lipid oxidation (P < 0.05) and higher glucose oxidation were observed in AMPKα2 KO (respiratory exchange ratio (RER) = 0.84 ± 0.02) than in WT and AMPKα1 KO (average RER = 0.80 ± 0.01) without genotype differences in muscle malonyl-CoA or free-carnitine concentrations. A similar increase in muscle pyruvate dehydrogenase kinase 4 (PDK4) mRNA expression in WT and AMPKα2 KO was observed following exercise, which is consistent with AMPKα2 deficiency not affecting the exercise-induced activation of the PDK4 transcriptional regulators HDAC4 and SIRT1. Interestingly, PDK4 protein content increased (63%, P < 0.001) in WT but remained unchanged in AMPKα2 KO. In accordance with the lack of increase in PDK4 protein content, lower (P < 0.01) inhibitory pyruvate dehydrogenase (PDH)-E1α Ser(293) phosphorylation was observed in AMPKα2 KO muscle compared to WT. These findings indicate that AMPKα2 regulates muscle metabolism post-exercise through inhibition of the PDH complex and hence glucose oxidation, subsequently creating conditions for increased fatty acid oxidation.
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Andreas Maechel
authors.initials: AM
authors.lastname: Fritzen
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.|Danish Diabetes Academy, Odense University Hospital, Odense, Denmark.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Lundsgaard
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.|Type 2 Diabetes and Obesity Pharmacology, Novo Nordisk A/S, Maaloev, Denmark.
authors.forename: Jacob
authors.initials: J
authors.lastname: Jeppesen
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Mette Landau Brabaek
authors.initials: ML
authors.lastname: Christiansen
authors.affiliation: Centre of Inflammation and Metabolism, the August Krogh Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Biensø
authors.affiliation: Cardiovascular Research Centre, Alberta Diabetes Institute, Department of Pediatrics, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jason R B
authors.initials: JR
authors.lastname: Dyck
authors.affiliation: Centre of Inflammation and Metabolism, the August Krogh Centre, Department of Biology, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Henriette
authors.initials: H
authors.lastname: Pilegaard
authors.affiliation: Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, the August Krogh Centre, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D006019:Glycolysis; D006655:Histone Deacetylases / Q000235:genetics / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000502:physiology; D005082:Physical Exertion; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism
chemical_list: C000631439:Pdk4 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; C470545:Sirt1 protein, mouse; D056564:Sirtuin 1; C498618:Hdac5 protein, mouse; D006655:Histone Deacetylases