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Selective activation of AMPK‐PGC‐1α or PKB‐TSC2‐mTOR signaling can explain specific adaptive responses to endurance or resistance training‐like electrical muscle stimulation
Abstract
Endurance training induces a partial fast-to-slow muscle phenotype transformation and mitochondrial biogenesis but no growth. In contrast, resistance training mainly stimulates muscle protein synthesis resulting in hypertrophy. The aim of this study was to identify signaling events that may mediate the specific adaptations to these types of exercise. Isolated rat muscles were electrically stimulated with either high frequency (HFS; 6x10 repetitions of 3 s-bursts at 100 Hz to mimic resistance training) or low frequency (LFS; 3 h at 10 Hz to mimic endurance training). HFS significantly increased myofibrillar and sarcoplasmic protein synthesis 3 h after stimulation 5.3- and 2.7-fold, respectively. LFS had no significant effect on protein synthesis 3 h after stimulation but increased UCP3 mRNA 11.7-fold, whereas HFS had no significant effect on UCP3 mRNA. Only LFS increased AMPK phosphorylation significantly at Thr172 by approximately 2-fold and increased PGC-1alpha protein to 1.3 times of control. LFS had no effect on PKB phosphorylation but reduced TSC2 phosphorylation at Thr1462 and deactivated translational regulators. In contrast, HFS acutely increased phosphorylation of PKB at Ser473 5.3-fold and the phosphorylation of TSC2, mTOR, GSK-3beta at PKB-sensitive sites. HFS also caused a prolonged activation of the translational regulators p70 S6k, 4E-BP1, eIF-2B, and eEF2. These data suggest that a specific signaling response to LFS is a specific activation of the AMPK-PGC-1alpha signaling pathway which may explain some endurance training adaptations. HFS selectively activates the PKB-TSC2-mTOR cascade causing a prolonged activation of translational regulators, which is consistent with increased protein synthesis and muscle growth. We term this behavior the "AMPK-PKB switch." We hypothesize that the AMPK-PKB switch is a mechanism that partially mediates specific adaptations to endurance and resistance training, respectively.
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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 (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 Atherton et al., 2005
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Metadata
- Authors
- Atherton, P. J., Babraj, J. A., Smith, K., Singh, J., Rennie, M. J., & Wackerhage, H.
- Affiliations
- University of Nottingham (GB)
- University of Dundee (GB)
- University of Lancashire (GB)
- ORCID
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2005-02-16
- Volume
- 19
- Issue
- 7
- Pages
- 1-23
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2115928938
- Cited by
- 475
- References
- 62
- Citations by year
- 2026: 9 · 2025: 11 · 2024: 10 · 2023: 21 · 2022: 15 · 2021: 15 · 2020: 18 · 2019: 25 · 2018: 35 · 2017: 16 · 2016: 22 · 2015: 20 · 2014: 30 · 2013: 33 · 2012: 23
- FWCI
- 12.47
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- CLOK (University of Central Lancashire) (submittedVersion)
- Funders
- National Institutes of Health (AR 49869)
- Biotechnology and Biological Sciences Research Council
- Diabetes UK
- Tenovus
- University of Central Lancashire
- University of Dundee
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- AMPK/PGC-1α signaling, neuromuscular electrical stimulation, high-frequency stimulation, low-frequency stimulation, endurance training adaptation, resistance training adaptation, muscle protein synthesis, muscle hypertrophy, mitochondrial biogenesis, UCP3, translational regulation, p70S6K, 4E-BP1
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Tuberous Sclerosis Complex 2 Protein, Adaptation, Physiological, Adenylate Kinase, Animals, Electric Stimulation, Enzyme Activation, Physical Exertion, Male, Muscle Contraction, Muscle Proteins, Myofibrils, Phosphorylation, Physical Conditioning, Animal, Physical Endurance, Protein Kinases, Sarcoplasmic Reticulum, Transcription Factors, Signal Transduction, RNA-Binding Proteins, Rats, Wistar, Muscle, Skeletal, Mitogen-Activated Protein Kinases, Tumor Suppressor Proteins, Proto-Oncogene Proteins c-akt, Rats, TOR Serine-Threonine Kinases
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