title: AMPKα is essential for acute exercise-induced gene responses but not for exercise training-induced adaptations in mouse skeletal muscle.
abstract: Exercise training increases skeletal muscle expression of metabolic proteins improving the oxidative capacity. Adaptations in skeletal muscle by pharmacologically induced activation of 5'-AMP-activated protein kinase (AMPK) are dependent on the AMPKα2 subunit. We hypothesized that exercise training-induced increases in exercise capacity and expression of metabolic proteins, as well as acute exercise-induced gene regulation, would be compromised in muscle-specific AMPKα1 and -α2 double-knockout (mdKO) mice. An acute bout of exercise increased skeletal muscle mRNA content of cytochrome c oxidase subunit I, glucose transporter 4, and VEGF in an AMPK-dependent manner, whereas cluster of differentiation 36 and fatty acid transport protein 1 mRNA content increased similarly in AMPKα wild-type (WT) and mdKO mice. During 4 wk of voluntary running wheel exercise training, the AMPKα mdKO mice ran less than WT. Maximal running speed was lower in AMPKα mdKO than in WT mice but increased similarly in both genotypes with exercise training. Exercise training increased quadriceps protein content of ubiquinol-cytochrome c reductase core protein 1 (UQCRC1), cytochrome c, hexokinase II, plasma membrane fatty acid-binding protein, and citrate synthase activity more in AMPKα WT than in mdKO muscle. However, analysis of a subgroup of mice matched for running distance revealed that only UQCRC1 protein content increased more in WT than in mdKO mice with exercise training. Thus, AMPKα1 and -α2 subunits are important for acute exercise-induced mRNA responses of some genes and may be involved in regulating basal metabolic protein expression but seem to be less important in exercise training-induced adaptations in metabolic proteins.
authors.affiliation: Section of Molecular Physiology, the August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Joachim
authors.identifier: http://orcid.org/0000-0002-9334-1298
authors.initials: J
authors.lastname: Fentz
authors.affiliation: Section of Molecular Physiology, the August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Rasmus
authors.initials: R
authors.lastname: Kjøbsted
authors.affiliation: Centre of Inflammation and Metabolism, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Caroline Maag
authors.initials: CM
authors.lastname: Kristensen
authors.affiliation: Section of Molecular Physiology, the August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Janne Rasmus
authors.initials: JR
authors.lastname: Hingst
authors.affiliation: Section of Molecular Physiology, the August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Jesper Bratz
authors.initials: JB
authors.lastname: Birk
authors.affiliation: Centre of Inflammation and Metabolism, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Anders
authors.initials: A
authors.lastname: Gudiksen
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Descartes, Sorbonne Paris Cité, Paris, France;
authors.forename: Marc
authors.initials: M
authors.lastname: Foretz
authors.affiliation: Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Medical and Health Sciences, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Peter
authors.identifier: http://orcid.org/0000-0001-7138-3211
authors.initials: P
authors.lastname: Schjerling
authors.affiliation: Institut National de la Sante et de la Recherche Medicale, U1016, Institut Cochin, Paris, France; CNRS, UMR8104, Paris, France; Université Descartes, Sorbonne Paris Cité, Paris, France;
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.affiliation: Centre of Inflammation and Metabolism, Department of Biology, University of Copenhagen, Copenhagen, Denmark;
authors.forename: Henriette
authors.initials: H
authors.lastname: Pilegaard
authors.affiliation: Section of Molecular Physiology, the August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; jwojtaszewski@nexs.ku.dk.
authors.forename: Jørgen F P
authors.identifier: http://orcid.org/0000-0001-9785-6830
authors.initials: JF
authors.lastname: Wojtaszewski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D052636:Allostasis; D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D005786:Gene Expression Regulation; D018345:Mice, Knockout; D008931:Mitochondria, Muscle / Q000201:enzymology / Q000378:metabolism; D009043:Motor Activity; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D013997:Time Factors; D015854:Up-Regulation
chemical_list: D009124:Muscle Proteins; D012333:RNA, Messenger; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: mitochondria; peroxisome proliferator-activated receptor-γ coactivator-1α; ubiquinol-cytochrome c reductase core protein 1; wheel running