An inducible knockout of dicer in adult mice does not affect endurance exercise-induced muscle adaptation

Satoshi Oikawa, Minjung Lee, Norio Motohashi, Seiji Maeda, Takayuki Akimoto

Research output: Contribution to journalArticle

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Abstract

The contractile and metabolic properties of adult skeletal muscle change in response to endurance exercise. The mechanisms of transcriptional regulation in exercise-induced skeletal muscle adaptation, including fiber-type switching and mitochondrial biogenesis, have been investigated intensively, whereas the role of microRNA (miRNA)-mediated posttranscriptional gene regulation is less well understood. We used tamoxifen-inducible Dicer1 knockout (iDicer KO) mice to reduce the global expression of miRNAs in adult skeletal muscle and subjected these mice to 2 wk of voluntary wheel running. Dicer mRNA expression was completely depleted in fast-twitch plantaris muscle after tamoxifen injection. However, several muscle-enriched miRNAs, including miR-1 and miR-133a, were reduced by only 30-50% in both the slow and fast muscles. The endurance exercise-induced changes that occurred for many parameters (i.e., fast-to-slow fiber-type switch and increases in succinate dehydrogenase, respiratory chain complex II, and citrate synthase activity) in wild type (WT) also occurred in the iDicer KO mice. Protein expression of myosin heavy chain IIa, peroxisome proliferator-activated receptor-γ coactivator-1α, and cytochrome c complex IV was also increased in the iDicer KO mice by the voluntary running. Furthermore, there was no significant difference in oxygen consumption rate in the isolated mitochondria between the WT and iDicer KO mice. These data indicate that muscle-enriched miRNAs were detectable even after 4 wk of tamoxifen treatment and there was no apparent specific endurance-exercise-induced muscle phenotype in the iDicer KO mice.

Original languageEnglish
Pages (from-to)C285-C292
JournalAmerican Journal of Physiology - Cell Physiology
Volume316
Issue number2
DOIs
Publication statusPublished - 2019 Feb 1

Fingerprint

Knockout Mice
MicroRNAs
Skeletal Muscle
Tamoxifen
Muscles
Running
Cytochromes c1
Citrate (si)-Synthase
Peroxisome Proliferator-Activated Receptors
Succinate Dehydrogenase
Myosin Heavy Chains
Organelle Biogenesis
Electron Transport
Oxygen Consumption
Mitochondria
Phenotype
Messenger RNA
Injections
Genes
Proteins

Keywords

  • Dicer
  • Endurance exercise
  • MicroRNAs
  • Mitochondria
  • Muscle fiber type

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

Cite this

An inducible knockout of dicer in adult mice does not affect endurance exercise-induced muscle adaptation. / Oikawa, Satoshi; Lee, Minjung; Motohashi, Norio; Maeda, Seiji; Akimoto, Takayuki.

In: American Journal of Physiology - Cell Physiology, Vol. 316, No. 2, 01.02.2019, p. C285-C292.

Research output: Contribution to journalArticle

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