High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression
- 1 February 2011
- journal article
- research article
- Published by American Physiological Society in Journal of Applied Physiology
- Vol. 110 (2), 309-317
- https://doi.org/10.1152/japplphysiol.00901.2010
Abstract
MicroRNAs (miRNA), small noncoding RNA molecules, may regulate protein synthesis, while resistance exercise training (RT) is an efficient strategy for stimulating muscle protein synthesis in vivo. However, RT increases muscle mass, with a very wide range of effectiveness in humans. We therefore determined the expression level of 21 abundant miRNAs to determine whether variation in these miRNAs was able to explain the variation in RT-induced gains in muscle mass. Vastus lateralis biopsies were obtained from the top and bottom ∼20% of responders from 56 young men who undertook a 5 day/wk RT program for 12 wk. Training-induced muscle mass gain was determined by dual-energy X-ray absorptiometry, and fiber size was evaluated by histochemistry. The expression level of each miRNA was quantified using TaqMan-based quantitative PCR, with the analysis carried out in a blinded manner. Gene ontology and target gene profiling were used to predict the potential biological implications. Of the 21 mature miRNAs examined, 17 were stable during RT in both groups. However, miR-378, miR-29a, miR-26a, and miR-451 were differentially expressed between low and high responders. miR-378, miR-29a, and miR-26a were downregulated in low responders and unchanged in high responders, while miR-451 was upregulated only in low responders. Interestingly, the training-induced change in miR-378 abundance was positively correlated with muscle mass gains in vivo. Gene ontology analysis of the target gene list of miR-378, miR-29a, miR-26a, and miR-451, from the weighted cumulative context ranking methodology, indicated that miRNA changes in the low responders may be compensatory, reflecting a failure to “activate” growth and remodeling genes. We report, for the first time, that RT-induced hypertrophy in human skeletal muscle is associated with selected changes in miRNA abundance. Our analysis indicates that miRNAs may play a role in the phenotypic change and pronounced intergroup variation in the RT response.Keywords
This publication has 52 references indexed in Scilit:
- mRNA and microRNA quality control for RT-qPCR analysisMethods, 2010
- Exercise training and protein metabolism: influences of contraction, protein intake, and sex-based differencesJournal of Applied Physiology, 2009
- The impact of microRNAs on protein outputNature, 2008
- Cluster analysis tests the importance of myogenic gene expression during myofiber hypertrophy in humansJournal of Applied Physiology, 2007
- MicroRNA-133 controls cardiac hypertrophyNature Medicine, 2007
- Improved scoring of functional groups from gene expression data by decorrelating GO graph structureBioinformatics, 2006
- The Role of MicroRNA-1 and MicroRNA-133 in Skeletal Muscle Proliferation and Differentiation.Nature Genetics, 2005
- ACTN3 and MLCK genotype associations with exertional muscle damageJournal of Applied Physiology, 2005
- Gene Ontology: tool for the unification of biologyNature Genetics, 2000
- Phosphorylation of p70S6kcorrelates with increased skeletal muscle mass following resistance exerciseAmerican Journal of Physiology-Cell Physiology, 1999