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Cited by 124Muscle Physiology and DisordersExercise and Physiological ResponsesCytokine Signaling Pathways and Interactions

Early Activation of Rat Skeletal Muscle IL-6/STAT1/STAT3 Dependent Gene Expression in Resistance Exercise Linked to Hypertrophy

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Begue, Gwénaëlle, Douillard, Aymeric, Galbes, Olivier, Rossano, Bernadette, Vernus, Barbara, Candau, Robin, Py, Guillaume·2013·PLoS ONE
DOI 10.1371/journal.pone.0057141PMC PMC3579782
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Abstract

Cytokine interleukin-6 (IL-6) is an essential regulator of satellite cell-mediated hypertrophic muscle growth through the transcription factor signal transducer and activator of transcription 3 (STAT3). The importance of this pathway linked to the modulation of myogenic regulatory factors expression in rat skeletal muscle undergoing hypertrophy following resistance exercise, has not been investigated. In this study, the phosphorylation and nuclear localization of STAT3, together with IL-6/STAT3-responsive gene expression, were measured after both a single bout of resistance exercise and 10 weeks of training. Flexor Digitorum Profundus muscle samples from Wistar rats were obtained 2 and 6 hours after a single bout of resistance exercise and 72 h after the last bout of either 2, 4, or 10 weeks of resistance training. We observed an increase in IL-6 and SOCS3 mRNAs concomitant with phosphorylation of STAT1 and STAT3 after 2 and 6 hours of a single bout of exercise (p<0.05). STAT3-dependent early responsive genes such as CyclinD1 and cMyc were also upregulated whereas MyoD and Myf5 mRNAs were downregulated (p<0.05). BrdU-positive satellite cells increased at 2 and 6 hours after exercise (p<0.05). Muscle fiber hypertrophy reached up to 100% after 10 weeks of training and the mRNA expression of Myf5, c-Myc and Cyclin-D1 decreased, whereas IL-6 mRNA remained upregulated. We conclude that the IL-6/STAT1/STAT3 signaling pathway and its responsive genes after a single bout of resistance exercise are an important event regulating the SC pool and behavior involved in muscle hypertrophy after ten weeks of training in rat skeletal muscle.

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  • A previous study using rats of the same age and weight showed that the non-exercised control group had a mean FDP CSA value of 1440 ± 84 μm2, which is notably lower than the value of 2291 ± 182 μm2 of the present trained control group.

    “However, in a previous study that used rats of the same age and weight, we showed that the non-exercised control group had a mean FDP CSA value of 1440 ± 84 μm2 [14], which is notably lower than the value of 2291 ± 182 μm2 of the present trained control group.”

    From Acute and chronic effects of <i>Rhaponticum carthamoides</i> and <i>Rhodiola rosea</i> extracts supplementation coupled to resistance exercise on muscle protein synthesis and mechanical power in rats (2020) · cites this paper as [14]

    Materials and Methods (Experimental design; page unavailable) identifies non-training control rats and FDP sampling. Results (Table 2; page unavailable) reports FDP cross-sectional areas by fiber type, but not the cited overall mean of 1440 ± 84 μm². The Animals section gives a weight of around 220 g but no age; the 2291 ± 182 μm² value is presented as the citing study’s own result, not this source’s. (LLM, conf=0.83)

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  • A rat model of resistance exercise is known to increase muscle protein synthesis.

    “We used a rat model of resistance exercise known to increase MPS [14].”

    From Acute and chronic effects of <i>Rhaponticum carthamoides</i> and <i>Rhodiola rosea</i> extracts supplementation coupled to resistance exercise on muscle protein synthesis and mechanical power in rats (2020) · cites this paper as [14]

    The Discussion reports that this rat resistance-training model produced muscle hypertrophy after 10 weeks and refers to an upregulation of protein synthesis as part of its interpretation. But its explicit account of increased protein synthesis after resistance exercise concerns humans; it does not report measuring MPS in the rats, so “known to increase MPS” overstates what this study establishes. (LLM, conf=0.83)

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Authors
Begue, G., Douillard, A., Galbes, O., Rossano, B., Vernus, B., Candau, R., & Py, G.
Affiliations
Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement (FR)
Corresponding author
Py, Guillaume
ORCID
Venue
PLoS ONE
Publisher
Public Library of Science (PLoS)
Published
2013-02-22
Volume
8
Issue
2
Pages
e57141
ISSN
1932-6203 (ISSN-L)
DOI
10.1371/journal.pone.0057141
PMC
PMC3579782
OpenAlex
W2031180727
Cited by
124
References
67
Citations by year
2026: 6 · 2025: 10 · 2024: 4 · 2023: 6 · 2022: 15 · 2021: 8 · 2020: 14 · 2019: 11 · 2018: 8 · 2017: 16 · 2016: 11 · 2015: 9 · 2014: 4 · 2013: 2
FWCI
3.88
Type
journal article
Language
en
Open access
Licence
Locations
  • PLoS ONE (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, other-oa)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • HAL (submittedVersion, other-oa)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Institut National de la Santé et de la Recherche Médicale
  • World Anti-Doping Agency
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
  • Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Keywords
interleukin-6, STAT3, STAT1, resistance training, skeletal muscle hypertrophy, satellite cells, SOCS3, myogenic regulatory factors, MyoD, Myf5, c-Myc, cyclin D1, flexor digitorum profundus, exercise-induced gene expression, muscle fiber hypertrophy
MeSH terms
Animals, Gene Expression Regulation, Male, Muscle Proteins, Physical Conditioning, Animal, RNA, Messenger, Interleukin-6, Polymerase Chain Reaction, Rats, Wistar, DNA Primers, Muscle, Skeletal, Cell Proliferation, STAT1 Transcription Factor, STAT3 Transcription Factor, Rats

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