title: AMPKα is critical for enhancing skeletal muscle fatty acid utilization during in vivo exercise in mice.
abstract: The importance of AMPK in regulation of fatty acid (FA) oxidation in skeletal muscle with contraction/exercise is unresolved. Using a mouse model lacking both AMPKα1 and -α2 in skeletal muscle specifically (mdKO), we hypothesized that FA utilization would be impaired in skeletal muscle. AMPKα mdKO mice displayed normal respiratory exchange ratio (RER) when fed chow or a high-fat diet, or with prolonged fasting. However, in vivo treadmill exercise at the same relative intensity induced a higher RER in AMPKα mdKO mice compared to wild-type (WT = 0.81 ± 0.01 (sem); mdKO = 0.87 ± 0.02 (sem); P < 0.01), indicating a decreased utilization of FA. Further, ex vivo contraction-induced FA oxidation was impaired in AMPKα mdKO muscle, suggesting that the increased RER during exercise originated from decreased skeletal muscle FA oxidation. A decreased muscle protein expression of CD36 (cluster of differentiation 36) and FABPpm (plasma membrane fatty acid binding protein) (by ∼17-40%), together with fully abolished TBC1D1 (tre-2/USP6, BUB2, cdc16 domain family member 1) Ser(237) phosphorylation during contraction/exercise in AMPKα mdKO mice, may impair FA transport capacity and FA transport protein translocation to sarcolemma, respectively. AMPKα is thus required for normal FA metabolism during exercise and muscle contraction.
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Joachim
authors.initials: J
authors.lastname: Fentz
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Rasmus
authors.initials: R
authors.lastname: Kjøbsted
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jesper B
authors.initials: JB
authors.lastname: Birk
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Andreas B
authors.initials: AB
authors.lastname: Jordy
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Jacob
authors.initials: J
authors.lastname: Jeppesen
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Kasper
authors.initials: K
authors.lastname: Thorsen
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Peter
authors.initials: P
authors.lastname: Schjerling
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Bente
authors.initials: B
authors.lastname: Kiens
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Niels
authors.initials: N
authors.lastname: Jessen
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Viollet
authors.affiliation: *Section of Molecular Physiology, August Krogh Centre, Department of Nutrition, Exercise and Sports, University of Copenhagen, Copenhagen, Denmark; Department of Molecular Medicine, Aarhus University Hospital, Aarhus, Denmark; Institute of Sports Medicine, Department of Orthopedic Surgery, Bispebjerg Hospital and Center for Healthy Aging, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; INSERM, U1016, Institute Cochin, Paris, France; Centre National de la Recherche Scientifique, Unités Mixtes de Recherche 8104, Paris, France; and Université Descartes, Sorbonne Paris Cité, Paris, France jwojtaszewski@nexs.ku.dk.
authors.forename: Jørgen F P
authors.initials: JF
authors.lastname: Wojtaszewski
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000502:physiology*; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001786:Blood Glucose / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D010766:Phosphorylation; D010805:Physical Conditioning, Animal / Q000502:physiology*; D012119:Respiration
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D005227:Fatty Acids; D009124:Muscle Proteins; C548179:Prkaa1 protein, mouse; C534978:Prkaa2 protein, mouse; D055372:AMP-Activated Protein Kinases
keywords: CD36; TBC1D1; fat oxidation; glucose uptake; physical activity