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Physiological Differences Between Low Versus High Skeletal Muscle Hypertrophic Responders to Resistance Exercise Training: Current Perspectives and Future Research Directions

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Roberts, Michael D., Haun, Cody T., Mobley, Christopher B., Mumford, Petey W., Romero, Matthew A., Roberson, Paul A., Vann, Christopher G., McCarthy, John J.·2018·Frontiers in Physiology
DOI 10.3389/fphys.2018.00834PMC PMC6039846
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Abstract

Numerous reports suggest there are low and high skeletal muscle hypertrophic responders following weeks to months of structured resistance exercise training (referred to as low and high responders herein). Specifically, divergent alterations in muscle fiber cross sectional area (fCSA), vastus lateralis thickness, and whole body lean tissue mass have been shown to occur in high versus low responders. Differential responses in ribosome biogenesis and subsequent protein synthetic rates during training seemingly explain some of this individual variation in humans, and mechanistic in vitro and rodent studies provide further evidence that ribosome biogenesis is critical for muscle hypertrophy. High responders may experience a greater increase in satellite cell proliferation during training versus low responders. This phenomenon could serve to maintain an adequate myonuclear domain size or assist in extracellular remodeling to support myofiber growth. High responders may also express a muscle microRNA profile during training that enhances insulin-like growth factor-1 (IGF-1) mRNA expression, although more studies are needed to better validate this mechanism. Higher intramuscular androgen receptor protein content has been reported in high versus low responders following training, and this mechanism may enhance the hypertrophic effects of testosterone during training. While high responders likely possess “good genetics”, such evidence has been confined to single gene candidates which typically share marginal variance with hypertrophic outcomes following training (e.g., different myostatin and IGF-1 alleles). Limited evidence also suggests pre-training muscle fiber type composition and self-reported dietary habits (e.g., calorie and protein intake) do not differ high versus low responders. Only a handful of studies have examined muscle biomarkers that are differentially expressed between low versus high responders. Thus, other molecular and physiological variables which could potentially affect the skeletal muscle hypertrophic response to resistance exercise training are also discussed including rDNA copy number, extracellular matrix and connective tissue properties, the inflammatory response to training, and mitochondrial as well as vascular characteristics.

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Crossref · 10.3389/fphys.2018.00834

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FIGURE 1 Factors which may or likely affect the skeletal muscle hypertrophic response to resistance exercise training. High skeletal muscle hypertrophic responders (HR) experience, on average, ∼80% in fiber cross sectional area (fCSA) or a 20–30% increase in muscle size following weeks to months of resistance exercise training. Low responders (LRs) experience virtually no change in fCSA or muscle size. Pre-training differences between clusters have included greater satellite cell number in high versus low responders; however, these findings have not replicated in other studies (indicated by ‘?’). Other speculative pre-training differences which may exist and need to be researched include connective tissue properties (e.g., fascia thickness, proteins related to extracellular matrix), genetic differences (e.g., multiple SNP candidates through GWAS), rDNA copy number differences, mitochondrial volume or function differences, or capillary differences (indicated by ‘???’). Following training, the observed phenotype in HR is influenced in part by superior increases in ribosome biogenesis and subsequent elevations in basal and post-exercise MPS. Limited evidence suggests HR experience superior training-induced increases in satellite cell number and satellite cell-mediated myonuclear addition as well as an altered micro RNA (miR) response to training to potentially enhance IGF-1 gene expression and increased androgen receptor protein content, although more research is needed to explore these areas. It is speculative whether HR experience superior increases in mitochondrial volume or capillary number following training relative to LR (indicated by ‘???’). It is also speculative whether LR experience a heightened inflammatory response to training (indicated by ‘???’).
FIGURE 1 Factors which may or likely affect the skeletal muscle hypertrophic response to resistance exercise training. High skeletal muscle hypertrophic responders (HR) experience, on average, ∼80% in fiber cross sectional area (fCSA) or a 20–30% increase in muscle size following weeks to months of resistance exercise training. Low responders (LRs) experience virtually no change in fCSA or muscle size. Pre-training differences between clusters have included greater satellite cell number in high versus low responders; however, these findings have not replicated in other studies (indicated by ‘?’). Other speculative pre-training differences which may exist and need to be researched include connective tissue properties (e.g., fascia thickness, proteins related to extracellular matrix), genetic differences (e.g., multiple SNP candidates through GWAS), rDNA copy number differences, mitochondrial volume or function differences, or capillary differences (indicated by ‘???’). Following training, the observed phenotype in HR is influenced in part by superior increases in ribosome biogenesis and subsequent elevations in basal and post-exercise MPS. Limited evidence suggests HR experience superior training-induced increases in satellite cell number and satellite cell-mediated myonuclear addition as well as an altered micro RNA (miR) response to training to potentially enhance IGF-1 gene expression and increased androgen receptor protein content, although more research is needed to explore these areas. It is speculative whether HR experience superior increases in mitochondrial volume or capillary number following training relative to LR (indicated by ‘???’). It is also speculative whether LR experience a heightened inflammatory response to training (indicated by ‘???’).CC BY · PubMed Central

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Metadata

Authors
Roberts, M. D., Haun, C. T., Mobley, C. B., Mumford, P. W., Romero, M. A., Roberson, P. A., Vann, C. G., & McCarthy, J. J.
Affiliations
  • Auburn University (US)
  • University of Kentucky (US)
Corresponding author
Roberts, Michael D.
ORCID
Venue
Frontiers in Physiology
Publisher
Frontiers Media SA
Published
2018-07-04
Volume
9
Pages
834-834
ISSN
1664-042X (ISSN-L)
DOI
10.3389/fphys.2018.00834
PMC
PMC6039846
OpenAlex
W2808102275
Cited by
107
References
154
Citations by year
2026: 8 · 2025: 11 · 2024: 13 · 2023: 12 · 2022: 10 · 2021: 13 · 2020: 20 · 2019: 19 · 2018: 1
FWCI
1.30
Type
journal article
Language
en
Open access
Licence
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • UKnowledge (University of Kentucky) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Nursing › Nutrition and Dietetics › Muscle metabolism and nutrition
  • Health Sciences › Medicine › Orthopedics and Sports Medicine › Sports Performance and Training
Keywords
skeletal muscle hypertrophy, resistance training, ribosome biogenesis, protein synthesis, satellite cell proliferation, myonuclear domain size, microRNA, insulin-like growth factor I, androgen receptor, myostatin, muscle fiber composition, protein intake, rDNA copy number, extracellular matrix, inflammation, mitochondrial function, vascular function, muscle fiber cross-sectional area, lean body mass

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