Cluster analysis reveals differential transcript profiles associated with resistance training-induced human skeletal muscle hypertrophy

• Published in: Physiological genomics Vol. 45; no. 12; pp. 499 - 507
• Main Authors: Thalacker-Mercer, Anna, Stec, Michael, Cui, Xiangqin, Cross, James, Windham, Samuel, Bamman, Marcas
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 17.06.2013
• Subjects: Cluster Analysis; Female; Gene Expression Profiling; Gene Expression Regulation; Gene Regulatory Networks - genetics; Humans; Hypertrophy - genetics; Inflammation - genetics; Inflammation - pathology; Male; Molecular Sequence Annotation; Muscle Development - genetics; Muscle, Skeletal - metabolism; Muscle, Skeletal - pathology; Resistance Training - adverse effects; RNA, Messenger - genetics; RNA, Messenger - metabolism; Signal Transduction - genetics; Translational Physiology; exercise; microarray; response clusters; growth
• ISSN: 1094-8341; 1531-2267; 1531-2267
• DOI: 10.1152/physiolgenomics.00167.2012

Using genomic microarray analysis, we sought to identify and annotate differences in the pretraining skeletal muscle transcriptomes among human subjects clustered as nonresponders (Non), modest responders (Mod), and extreme responders (Xtr) based on differential magnitudes of myofiber hypertrophy in response to progressive resistance training (RT) (Non −16 μm 2 , Mod 1,111 μm 2 , or Xtr 2,475 μm 2 ). In prior work, we noted differences among clusters in the prevalence of myogenic stem cells prior to and during RT ( 35 ), and in the translational signaling responses to the first bout of resistance exercise ( 30 ). Here we identified remarkable differences in the pretraining transcript profiles among clusters (8,026 gene transcripts differentially expressed between Xtr and Non, 2,463 between Xtr and Mod, and 1,294 between Mod and Non). Annotated functions and networks of differentially expressed genes suggest Xtr were “primed” to respond to RT through transcriptional regulation, along with a uniquely expressed network of genes involved in skeletal muscle development, while the failed response in Non may have been driven by excessive proinflammatory signaling. Protein follow-up analysis revealed higher basal levels of acetylated histone H3 (K36) in the two responder clusters (Mod, Xtr) compared with Non, and only the responders experienced alterations in the muscle content of select proteins (e.g., α-tubulin, p27 kip ) in response to the first resistance exercise stimulus. Overall, the widely disparate transcriptomes identified prior to RT among the three clusters support the notion that at least some of the interindividual heterogeneity in propensity for RT-induced myofiber hypertrophy is likely predetermined.