Biomarkers associated with low, moderate, and high vastus lateralis muscle hypertrophy following 12 weeks of resistance training
Open accessAbstract
We sought to identify biomarkers which delineated individual hypertrophic responses to resistance training. Untrained, college-aged males engaged in full-body resistance training (3 d/wk) for 12 weeks. Body composition via dual x-ray absorptiometry (DXA), vastus lateralis (VL) thickness via ultrasound, blood, VL muscle biopsies, and three-repetition maximum (3-RM) squat strength were obtained prior to (PRE) and following (POST) 12 weeks of training. K-means cluster analysis based on VL thickness changes identified LOW [n = 17; change (mean±SD) = +0.11±0.14 cm], modest (MOD; n = 29, +0.40±0.06 cm), and high (HI; n = 21, +0.69±0.14 cm) responders. Biomarkers related to histology, ribosome biogenesis, proteolysis, inflammation, and androgen signaling were analyzed between clusters. There were main effects of time (POST>PRE, p<0.05) but no cluster×time interactions for increases in DXA lean body mass, type I and II muscle fiber cross sectional area and myonuclear number, satellite cell number, and macronutrients consumed. Interestingly, PRE VL thickness was ~12% greater in LOW versus HI (p = 0.021), despite POST values being ~12% greater in HI versus LOW (p = 0.006). However there was only a weak correlation between PRE VL thickness scores and change in VL thickness (r2 = 0.114, p = 0.005). Forced post hoc analysis indicated that muscle total RNA levels (i.e., ribosome density) did not significantly increase in the LOW cluster (351±70 ng/mg to 380±62, p = 0.253), but increased in the MOD (369±115 to 429±92, p = 0.009) and HI clusters (356±77 to 470±134, p<0.001; POST HI>POST LOW, p = 0.013). Nonetheless, there was only a weak association between change in muscle total RNA and VL thickness (r2 = 0.079, p = 0.026). IL-1β mRNA levels decreased in the MOD and HI clusters following training (p<0.05), although associations between this marker and VL thickness changes were not significant (r2 = 0.0002, p = 0.919). In conclusion, individuals with lower pre-training VL thickness values and greater increases muscle total RNA levels following 12 weeks of resistance training experienced greater VL muscle growth, although these biomarkers individually explained only ~8-11% of the variance in hypertrophy.
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Because DNA content represents the total number of myonuclei, an increasing RNA:DNA ratio demonstrates that existing individual nucleoli are upregulating transcription and expanding their individual factory output.
“Because the DNA content represents the total number of myonuclei—assuming satellite cell fusion is accounted for—an increasing RNA:DNA ratio explicitly demonstrates that existing individual nucleoli are successfully upregulating their transcription and expanding their individual factory output [77].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [77]
The Results (Changes in ribosome biogenesis markers between clusters; page unavailable) report increased total RNA but decreased 45S pre-rRNA after training. The Discussion says this pattern potentially reflects downregulation of rDNA transcription, rather than demonstrating that individual nucleoli upregulated transcription. The paper does not report an RNA:DNA ratio, and it cautions that its transcription proxy limits definitive conclusions. (LLM, conf=0.82)
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Experimental — accuracy not yet measuredNormalizing total RNA abundance to stable DNA content, generating an RNA:DNA ratio, provides a substantially more accurate reflection of translational capacity expansion.
“Normalizing total RNA abundance to stable DNA content (generating an RNA:DNA ratio) provides a substantially more accurate reflection of translational capacity expansion [77].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [77]
The Discussion describes ribosome density as total RNA per weight of assayed muscle, and the Results report changes in total RNA. Neither section addresses normalizing RNA to stable DNA content or whether an RNA:DNA ratio more accurately reflects translational capacity (searched: RNA:DNA ratio, DNA normalization). Page numbers were not available in our copy. (LLM, conf=0.74)
Experimental — accuracy not yet measuredMuch apparent inconsistency in the prior literature can be traced to authors selecting a single denominator without acknowledging the assumptions it implies, not to one method being wrong.
“Much of the apparent inconsistency in the prior literature can be traced not to one method being wrong but to authors selecting a single denominator without acknowledging the assumptions it implies [37,77].”
From Ribosome Biogenesis as a Putative Bottleneck to Skeletal Muscle Hypertrophy: Mechanisms, Human Evidence, and Practical Modulators (2026) · cites this paper as [77]
The Discussion’s Experimental considerations section says ultrasound and histological fiber measurements may disagree because people differ in muscle-fiber number. It does not address the claimed explanation for inconsistencies in prior literature: authors choosing a single denominator without acknowledging its assumptions. Searches for denominator and normalization did not locate that point in our copy; page numbers were not available. (LLM, conf=0.74)
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References 51 · Cited by 112
- Authors
- Mobley, C. B., Haun, C. T., Roberson, P. A., Mumford, P. W., Kephart, W. C., Romero, M. A., Osburn, S. C., Vann, C. G., Young, K. C., Beck, D. T., Martin, J. S., Lockwood, C. M., & Roberts, M. D.
- Affiliations
- Auburn University (US)
- Corresponding author
- Roberts, Michael D.
- ORCID
- Venue
- PLOS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2018-04-05
- Volume
- 13
- Issue
- 4
- Pages
- e0195203
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC5886420
- OpenAlex
- W2796380044
- Cited by
- 112
- References
- 51
- Citations by year
- 2026: 9 · 2025: 14 · 2024: 11 · 2023: 10 · 2022: 12 · 2021: 15 · 2020: 9 · 2019: 16 · 2018: 16
- FWCI
- 4.98
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS ONE (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- Funders
- Hilmar Ingredients
- Bionutritional Research Group
- 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 › Orthopedics and Sports Medicine › Sports Performance and Training
- Keywords
- muscle hypertrophy, vastus lateralis, resistance training, biomarkers, muscle fiber cross-sectional area, myonuclear number, satellite cells, ribosome biogenesis, IL-1β, interleukin-6, TNF-α, androgen signaling, proteolysis, inflammation, lean body mass, squat strength, muscle biopsy
- MeSH terms
- Adult, Androgens, Body Composition, Humans, Hypertrophy, Ribosomes, Ultrasonography, Signal Transduction, Biomarkers, Exercise, Gene Expression, Cluster Analysis, Muscle, Skeletal, Muscle Fibers, Skeletal, Micronutrients, Satellite Cells, Skeletal Muscle, Muscle Strength, Resistance Training, Young Adult, Self Report
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