Muscle specific microRNAs are regulated by endurance exercise in human skeletal muscle

Abstract

Muscle specific miRNAs, myomiRs, have been shown to control muscle development in vitro and are differentially expressed at rest in diabetic skeletal muscle. Therefore, we investigated the expression of these myomiRs, including miR-1, miR-133a, miR-133b and miR-206 in muscle biopsies from vastus lateralis of healthy young males (n = 10) in relation to a hyperinsulinaemic-euglycaemic clamp as well as acute endurance exercise before and after 12 weeks of endurance training. The subjects increased their endurance capacity,V O 2 max (l min −1 ) by 17.4% (P < 0.001), and improved insulin sensitivity by 19% (P < 0.01). While myomiR expression remained stable during a hyperinsulinaemic-euglycaemic clamp, an acute bout of exercise increased mir-1 (P < 0.05) and mir-133a (P < 0.05) expression before, but not after, training. In resting biopsies, endurance training for 12 weeks decreased basal expression of all four myomiRs (P < 0.05). Interestingly, all myomiRs reverted to their pre-training expression levels 14 days after ceasing the training programme. Components of major pathways involved in endurance adaptation such as MAPK and TGF-β were predicted to be targeted by the myomiRs examined. Tested predicted target proteins included Cdc42 and ERK 1/2. Although these proteins were downregulated between post-training period and 2 weeks of cessation, an inverse correlation between myomiR and target proteins was not found. In conclusion, our data suggest myomiRs respond to physiological stimuli, but their role in regulating human skeletal muscle adaptation remains unknown.

Exercise Therapy for Physical Therapist

“…Exercise training, both acute endurance and resistance in healthy male volunteers, was shown to enhance miR-133 expression in the vastus lateralis muscles [34,35]. Moreover, endurance exercise elevated circulating levels of miR-133 in healthy individuals after either an acute bout of aerobic exercise, or endurance training [36,37].…”

Exercício físico e microRNAs: novas fronteiras na insuficiência cardíaca

“…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. Interestingly, these levels return to baseline after 14 days of its discontinuation.…”

Signaling Pathways that Mediate Skeletal Muscle Hypertrophy: Effects of Exercise Training

“…The expression of myomiRNAs is dramatically increased during myogenesis. Furthermore, differential expression of myomiRNAs following resistance exercise in skeletal muscle suggests that myomiRNAs play a role in human health [115].…”

“…These precursor (pre-miRNAs) are transported to the cytoplasm by the nuclear export protein, Exportin 5, where they are further processed by the RNAse Dicer, giving rise to the mature miRNA and its complementary strand from the stem-loop, referred to as the ´star` strand [5]. The mature miRNA is incorporated into the RNA-induced silencing complex (RISC), where acts by hybridizing either perfectly or partially to complementary binding sites located in the 3`UTRs of target mRNAs, promoting translational repression or degradation [115,119] (Figure 3). Recent evidence supports a role for miRNAs as integral components of the regulatory circuitry for muscle development [120].…”

“…Recent studies have revealed that, in addition to activating genes involved in muscle differentiation and muscle contraction, these myogenic transcription factors activate the expression of a set of conserved microRNAs (miRNAs) that function to "fine-tune" the output of these transcriptional networks, resulting in accurate cellular responses to developmental, physiologic and pathologic signals [114][115][116].…”