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

• Published in: The Journal of physiology Vol. 588; no. 20; pp. 4029 - 4037
• Main Authors: Nielsen, Søren, Scheele, Camilla, Yfanti, Christina, Åkerström, Thorbjörn, Nielsen, Anders R., Pedersen, Bente K., Laye, Matthew
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 15.10.2010; Wiley Subscription Services, Inc; Blackwell Science Inc
• Subjects: Adult; Analysis of Variance; Biopsy; Blotting, Western; Body Composition - physiology; Exercise - physiology; Gene expression; Glucose Clamp Technique; Humans; Male; MicroRNAs; MicroRNAs - physiology; Muscle, Skeletal - physiology; Musculoskeletal system; Oxygen Consumption - physiology; Physical Endurance - physiology; Proteins; Signal Transduction - physiology; Skeletal Muscle and Exercise
• ISSN: 0022-3751; 1469-7793
• DOI: 10.1113/jphysiol.2010.189860

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, (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. MicroRNAs are small non‐coding RNAs which negatively regulate gene expression. The muscle specific microRNAs (myomiRs) play an important role in muscle development, thus implicating a role for them in muscle adaptation to exercise. We show, in young healthy men, that endurance exercise alters the regulation of myomiRs and that predicted exercise target proteins partly follow the expression pattern of the myomiRs. We further demonstrate that the myomiR response to acute exercise differs from the long‐term training response. While two out of four myomiRs increased in response to acute exercise, all four myomiRs decreased in response to 12 weeks of endurance training. Following 2 weeks of non‐training, the myomiRs were back at the expression level observed before the training period. In contrast to a recently published study, we found no relation between insulin and myomiR expression. Our data contribute to the understanding of the complex mechanisms behind training adaption in human skeletal muscle.