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Cited by 274Metabolism, Diabetes, and CancerCardiovascular and exercise physiologyAdipose Tissue and Metabolism

Effects of α‐AMPK knockout on exercise‐induced gene activation in mouse skeletal muscle

Jørgensen, Sebastian B., Wojtaszewski, Jørgen F. P., Viollet, Benoit, Andreelli, Fabrizio, Birk, Jesper B., Hellsten, Ylva, Schjerling, Peter, Vaulont, Sophie +3 more·2005·The FASEB Journal
DOI 10.1096/fj.04-3144fje
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Abstract

We tested the hypothesis that 5'AMP-activated protein kinase (AMPK) plays an important role in regulating the acute, exercise-induced activation of metabolic genes in skeletal muscle, which were dissected from whole-body alpha2- and alpha1-AMPK knockout (KO) and wild-type (WT) mice at rest, after treadmill running (90 min), and in recovery. Running increased alpha1-AMPK kinase activity, phosphorylation (P) of AMPK, and acetyl-CoA carboxylase (ACC)beta in alpha2-WT and alpha2-KO muscles and increased alpha2-AMPK kinase activity in alpha2-WT. In alpha2-KO muscles, AMPK-P and ACCbeta-P were markedly lower compared with alpha2-WT. However, in alpha1-WT and alpha1-KO muscles, AMPK-P and ACCbeta-P levels were identical at rest and increased similarly during exercise in the two genotypes. The alpha2-KO decreased peroxisome-proliferator-activated receptor gamma coactivator (PGC)-1alpha, uncoupling protein-3 (UCP3), and hexokinase II (HKII) transcription at rest but did not affect exercise-induced transcription. Exercise increased the mRNA content of PGC-1alpha, Forkhead box class O (FOXO)1, HKII, and pyruvate dehydrogenase kinase 4 (PDK4) similarly in alpha2-WT and alpha2-KO mice, whereas glucose transporter GLUT 4, carnitine palmitoyltransferase 1 (CPTI), lipoprotein lipase, and UCP3 mRNA were unchanged by exercise in both genotypes. CPTI mRNA was lower in alpha2-KO muscles than in alpha2-WT muscles at all time-points. In alpha1-WT and alpha1-KO muscles, running increased the mRNA content of PGC-1alpha and FOXO1 similarly. The alpha2-KO was associated with lower muscle adenosine 5'-triphosphate content, and the inosine monophosphate content increased substantially at the end of exercise only in alpha2-KO muscles. In addition, subcutaneous injection of 5-aminoimidazole-4-carboxamide-1-beta-4-ribofuranoside (AICAR) increased the mRNA content of PGC-1alpha, HKII, FOXO1, PDK4, and UCP3, and alpha2-KO abolished the AICAR-induced increases in PGC-1alpha and HKII mRNA. In conclusion, KO of the alpha2- but not the alpha1-AMPK isoform markedly diminished AMPK activation during running. Nevertheless, exercise-induced activation of the investigated genes in mouse skeletal muscle was not impaired in alpha1- or alpha2-AMPK KO muscles. Although it cannot be ruled out that activation of the remaining alpha-isoform is sufficient to increase gene activation during exercise, the present data do not support an essential role of AMPK in regulating exercise-induced gene activation in skeletal muscle.

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Crossref · 10.1096/fj.04-3144fje

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  • Endurance exercise studies with rodents and humans have shown AMPK signaling and mRNAs involved in mitochondrial biogenesis increase hours following exercise.

    “endurance exercise studies with rodents and humans have shown AMPK signaling and mRNAs involved in mitochondrial biogenesis increase hours following exercise (Fujii et al., 2000; Atherton et al., 2005; Jorgensen et al., 2005)”

    From Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities (2021) · cites this paper as Jorgensen et al., 2005

  • LKB1-MKO and AMPK α2 KO, β2 KO and α2 KD mice have lower starting glycogen levels in skeletal muscle.

    “LKB1-MKO and AMPK α2 KO, β2 KO and α2 KD mice have lower starting glycogen levels in skeletal muscle [17,138-140], supporting a role for AMPK in glycogen synthesis.”

    From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [138]

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Authors
Jørgensen, S. B., Wojtaszewski, J. F. P., Viollet, B., Andreelli, F., Birk, J. B., Hellsten, Y., Schjerling, P., Vaulont, S., Neufer, P. D., Richter, E. A., & Pilegaard, H.
Affiliations
  • University of Copenhagen (DK)
  • Copenhagen Muscle Research Centre Institut Cochin INSERM, CNRS Rene Descartes University Department of Genetic Development and Molecular Pathology Paris France
  • Rigshospitalet (DK)
  • Centre National de la Recherche Scientifique (FR)
  • Yale University (US)
ORCID
Venue
The FASEB Journal
Publisher
Wiley
Published
2005-05-05
Volume
19
Issue
9
Pages
1146-1148
ISSN
  • 0892-6638 (ISSN-L)
  • 1530-6860
DOI
10.1096/fj.04-3144fje
OpenAlex
W2125732396
Cited by
274
References
59
Citations by year
2026: 4 · 2025: 3 · 2024: 6 · 2023: 6 · 2022: 2 · 2021: 8 · 2020: 14 · 2019: 14 · 2018: 13 · 2017: 10 · 2016: 13 · 2015: 12 · 2014: 12 · 2013: 19 · 2012: 13
FWCI
7.28
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations
  • The FASEB Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Danmarks Grundforskningsfond (504‐14)
  • Sundhed og Sygdom, Det Frie Forskningsråd
  • Novo Nordisk Fonden
  • Center for Muskelforskning (LSHM‐CT‐2004‐005272)
  • European Commission
  • University of Dundee
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
  • Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
Keywords
AMPK, skeletal muscle, exercise-induced gene expression, PGC-1α, FOXO1, ACACB, hexokinase 2, PDK4, UCP3, carnitine palmitoyltransferase 1, AICAR, muscle energy metabolism, inosine monophosphate
MeSH terms
Uncoupling Protein 3, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Acetyl-CoA Carboxylase, Adenosine Monophosphate, Adenosine Triphosphate, Aminoimidazole Carboxamide, Animals, Carrier Proteins, Female, Gene Expression Regulation, Glycogen, Hexokinase, Inosine Monophosphate, Ion Channels, Male, Multienzyme Complexes, Physical Conditioning, Animal, Protein Kinases, Ribonucleotides, RNA, Messenger, Transcription Factors, Transcription, Genetic, Transcriptional Activation, Trans-Activators, Protein Serine-Threonine Kinases, Mice, Knockout, Muscle, Skeletal, Mitochondrial Proteins, Mice, AMP-Activated Protein Kinases

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