High responders to resistance exercise training demonstrate differential regulation of skeletal muscle microRNA expression

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.

Heterogeneity in resistance training-induced muscle strength and mass responses in men and women of different ages

“…In previous studies with healthy human subjects, e.g., several genetic variations (Riechman et al 2004;Devaney et al 2009;Walsh et al 2012;Van Deveire et al 2012), differences in skeletal muscle gene Raue et al 2012;Phillips et al 2013) and microRNA expression (Davidsen et al 2011), phosphorylation status of signaling proteins (Mayhew et al 2011;Mitchell et al 2013), androgen receptor concentrations (Ahtiainen et al 2011;Mitchell et al 2013), and satellite cell count (Petrella et al 2008) have been suggested to segregate high and low responders to RTinduced muscle hypertrophy. The physiological aspects of individual variation in phenotype responses to RT are apparently very complex phenomena and more studies specifically focused on high and low responders are required to reveal unambiguously the mechanisms of individual differences in RT-induced adaptations.…”

“…The robust study of individual responses to unilateral upper arm RT by Hubal et al (2005) showed that of 585 subjects, approximately 6 % showed practically no gains in muscle size. Also, other RT studies have reported that, in some subjects, muscle size gains are either minimal or non-existent following a training period Davidsen et al 2011;Raue et al 2012;Mitchell et al 2013;Phillips et al 2013). Similarly to muscle size responses, gains in muscle strength during RT are also highly individual (Hubal et al 2005;Erskine et al 2010).…”

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“…miRNAs have been shown to be involved in muscle cell development (Luo, Nie, & Zhang, 2013), respond to exercise both acutely and chronically (Russell et al, 2013) and be predictive of response to training (Davidsen et al, 2011).…”

Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca

“…There are several miRNAs present in skeletal muscle, and miRs-1, -133a, -133b and -206 comprise 25% of them, often being referred to as "myomirs" 47 . In healthy subjects, these four myomirs decrease significantly after 12 weeks of aerobic training 48 , indicating that they adjust quickly to the level of physical activity.…”

“…This variability is also accompanied by differences in the behavior of miRNAs. A study 47 that analyzed biopsies of the vastus lateralis muscle of 56 men undergoing resistance training for 12 weeks found that the expression of miR-378 decreased and that of miR-478 increased, both significantly, only in those who responded little to the training. In addition, there was a strong correlation between the variation in the expression of miR-378 with the gain in lean body mass.…”