Biomarkers associated with low, moderate, and high vastus lateralis muscle hypertrophy following 12 weeks of resistance training

PLoS One. 2018 Apr 5;13(4):e0195203. doi: 10.1371/journal.pone.0195203. eCollection 2018.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Androgens / metabolism
  • Biomarkers*
  • Body Composition
  • Cluster Analysis
  • Exercise*
  • Gene Expression
  • Humans
  • Hypertrophy
  • Micronutrients
  • Muscle Fibers, Skeletal / cytology
  • Muscle Fibers, Skeletal / physiology
  • Muscle Strength
  • Muscle, Skeletal / anatomy & histology*
  • Muscle, Skeletal / diagnostic imaging
  • Muscle, Skeletal / physiology*
  • Resistance Training*
  • Ribosomes
  • Satellite Cells, Skeletal Muscle / cytology
  • Satellite Cells, Skeletal Muscle / physiology
  • Self Report
  • Signal Transduction
  • Ultrasonography
  • Young Adult


  • Androgens
  • Biomarkers
  • Micronutrients

Grants and funding

The authors have no conflicts of interest to disclose regarding the publication of these data. Funding for participant compensation was provided by gift monies donated to M.D.R. through Hilmar Ingredients (Hilmar, CA, USA) and Bionutritional Research Group (Irvine, CA, USA), and Lockwood LLC (C.M.L., Draper, UT, USA) solicited these donations. Reagent costs were made possible through discretionary laboratory funds (M.D.R.). The authors would like to thank the participants for devoting their time to the completion of this study.