Skeletal muscles contain several subtypes of myofibers that differ in contractile and metabolic properties. Transcriptional control of fiber-type specification and adaptation has been intensively investigated over the past several decades. Recently, microRNA (miRNA)-mediated posttranscriptional gene regulation has attracted increasing attention. MiR-23a targets key molecules regulating contractile and metabolic properties of skeletal muscle, such as myosin heavy-chains and peroxisome proliferator-activated receptor gamma, coactivator 1 alpha (PGC-1α). In the present study, we analyzed the skeletal muscle phenotype of miR-23a transgenic (miR-23a Tg) mice to explore whether forced expression of miR-23a affects markers of mitochondrial content, muscle fiber composition, and muscle adaptations induced by 4 weeks of voluntary wheel running. When compared with wild-type mice, protein markers of mitochondrial content, including PGC-1α, and cytochrome c oxidase complex IV (COX IV), were significantly decreased in the slow soleus muscle, but not the fast plantaris muscle of miR-23a Tg mice. There was a decrease in type IId/x fibers only in the soleus muscle of the Tg mice. Following 4 weeks of voluntary wheel running, there was no difference in the endurance exercise capacity as well as in several muscle adaptive responses including an increase in muscle mass, capillary density, or the protein content of myosin heavy-chain IIa, PGC-1α, COX IV, and cytochrome c. These results show that miR-23a targets PGC-1α and regulates basal metabolic properties of slow but not fast twitch muscles. Elevated levels of miR-23a did not impact on whole body endurance capacity or exercise-induced muscle adaptations in the fast plantaris muscle.
Bibliographical noteFunding Information:
The authors thank Dr. Hiroshi Sagara (The University of Tokyo) and Akisa Tobimatsu for excellent technical support. The authors also thank Dr. Stefano Schiaffino (Venetian Institute for Molecular Medicine) for comments on EM images. This study was supported in part by Grants-in Aid for Young Investigators (A; 21680049 to T. A.) and for Scientific Research (B; 25282198 to T. A.) from the Ministry of Education, Culture, Sports, Science and Technology, Japan, and the Takeda Science Foundation. S. W., K. A. and J. H. P. were supported by Japan Society of the Promotion of Science (JSPS).
© 2014, Springer-Verlag Berlin Heidelberg.
- Endurance performance
- Muscle fiber type
- Peroxisome proliferator-activated receptor gamma, coactivator 1 alpha
ASJC Scopus subject areas
- Clinical Biochemistry
- Physiology (medical)