Cited by 36Muscle Physiology and DisordersMuscle metabolism and nutritionCardiovascular and exercise physiology

Increased hypertrophic response with increased mechanical load in skeletal muscles receiving identical activity patterns

Eftestøl, Einar, Egner, Ingrid M., Lunde, Ida G., Ellefsen, Stian, Andersen, Tom, Sjåland, Cecilie, Gundersen, Kristian, Bruusgaard, Jo C.·2016·American Journal of Physiology-Cell Physiology

Abstract

It is often assumed that mechanical factors are important for effects of exercise on muscle, but during voluntary training and most experimental conditions the effects could solely be attributed to differences in electrical activity, and direct evidence for a mechanosensory pathway has been scarce. We here show that, in rat muscles stimulated in vivo under deep anesthesia with identical electrical activity patterns, isometric contractions induced twofold more hypertrophy than contractions with 50-60% of the isometric force. The number of myonuclei and the RNA levels of myogenin and myogenic regulatory factor 4 were increased with high load, suggesting that activation of satellite cells is mechano dependent. On the other hand, training induced a major shift in fiber type distribution from type 2b to 2x that was load independent, indicating that the electrical signaling rather than mechanosignaling controls fiber type. RAC-α serine/threonine-protein kinase (Akt) and ribosomal protein S6 kinase β-1 (S6K1) were not significantly differentially activated by load, suggesting that the differences in mechanical factors were not important for activating the Akt/mammalian target of rapamycin/S6K1 pathway. The transmembrane molecule syndecan-4 implied in overload hypertrophy in cardiac muscle was not load dependent, suggesting that mechanosignaling in skeletal muscle is different.

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Crossref · 10.1152/ajpcell.00016.2016

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Authors
Eftestøl, E., Egner, I. M., Lunde, I. G., Ellefsen, S., Andersen, T., Sjåland, C., Gundersen, K., & Bruusgaard, J. C.
Affiliations
  • University of Oslo (NO)
  • Oslo University Hospital (NO)
  • Lillehammer University College (NO)
Corresponding author
Bruusgaard, Jo C.
Venue
American Journal of Physiology-Cell Physiology
Published
2016-10-01
Volume
311
Issue
4
Pages
C616-C629
ISSN
  • 0363-6143 (ISSN-L)
  • 1522-1563
OpenAlex
W2480587261
Cited by
36
References
147
Citations by year
2026: 2 · 2025: 3 · 2024: 1 · 2023: 2 · 2022: 2 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 4 · 2017: 5
FWCI
2.60
Type
journal article
Language
en
Open access
closed
Locations
  • American Journal of Physiology-Cell Physiology (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Regional Science Fund (203961)
  • Research Council of Norway
  • Stiftelsen Kristian Gerhard Jebsen
  • Anders Jahre's fund for the promotion of science, Norway
  • The South Eastern Regional Health authority, Norway
  • Simon Fougner Hartmann's Family fund, Denmark
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
Keywords
skeletal muscle hypertrophy, mechanical loading, mechanosensing, electrical stimulation, isometric contraction, satellite cells, myonuclei, myogenin, fiber type shift, syndecan-4, voluntary exercise
MeSH terms
Animals, Hypertrophy, Isometric Contraction, Signal Transduction, Rats, Sprague-Dawley, Myogenin, Muscle, Skeletal, Ribosomal Protein S6 Kinases, Proto-Oncogene Proteins c-akt, Rats, TOR Serine-Threonine Kinases

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