miRNA in the Regulation of Skeletal Muscle Adaptation to Acute Endurance Exercise in C57Bl/6J Male Mice

Abstract

MicroRNAs (miRNAs) are evolutionarily conserved small non-coding RNA species involved in post-transcriptional gene regulation. In vitro studies have identified a small number of skeletal muscle-specific miRNAs which play a crucial role in myoblast proliferation and differentiation. In skeletal muscle, an acute bout of endurance exercise results in the up-regulation of transcriptional networks that regulate mitochondrial biogenesis, glucose and fatty acid metabolism, and skeletal muscle remodelling. The purpose of this study was to assess the expressional profile of targeted miRNA species following an acute bout of endurance exercise and to determine relationships with previously established endurance exercise responsive transcriptional networks. C57Bl/6J wild-type male mice (N = 7/group) were randomly assigned to either sedentary or forced-endurance exercise (treadmill run @ 15 m/min for 90 min) group. The endurance exercise group was sacrificed three hours following a single bout of exercise. The expression of miR- 181, 1, 133, 23, and 107, all of which have been predicted to regulate transcription factors and co-activators involved in the adaptive response to exercise, was measured in quadriceps femoris muscle. Endurance exercise significantly increased the expression of miR-181, miR-1, and miR-107 by 37%, 40%, and 56%, respectively, and reduced miR-23 expression by 84% (P≤0.05 for all), with no change in miR-133. Importantly, decreased expression of miRNA-23, a putative negative regulator of PGC-1α was consistent with increased expression of PGC-1α mRNA and protein along with several downstream targets of PGC-1α including ALAS, CS, and cytochrome c mRNA. PDK4 protein content remains unaltered despite an increase in its putative negative regulator, miR-107, and PDK4 mRNA expression. mRNA expression of miRNA processing machinery (Drosha, Dicer, and DGCR8) remained unchanged. We conclude that miRNA-mediated post-transcriptional regulation is potentially involved in the complex regulatory networks that govern skeletal muscle adaptation to endurance exercise in C57Bl/6J male mice.

Exercise Increases Mitochondrial PGC-1α Content and Promotes Nuclear-Mitochondrial Cross-talk to Coordinate Mitochondrial Biogenesis

“…Animal Housing and Exercise Protocol-C57Bl/6J mice, bred in an institutional central animal facility (McMaster University), were housed in micro-isolator cages in a temperature-and humidity-controlled room and maintained on a 12-h light-dark cycle with food and water ad libitum (20). At 3 months of age, mice (n ϭ 12/group; Ǩ ϭ () were matched for body weight and randomly assigned to either sedentary (SED), forced-endurance (END) exercise, or forced endurance followed by 3 h of recovery (ENDϩ3h) group.…”

MicroRNA-149 Inhibits PARP-2 and Promotes Mitochondrial Biogenesis via SIRT-1/PGC-1α Network in Skeletal Muscle

“…This suggests that inhibition of PARP activities is beneficial to promote skeletal muscle energy expenditure. One promising strategy to inhibit the activity of endogenous PARPs would be modulation of the miRNA-mediated pathway, which plays a key role in skeletal muscle metabolism (22,(29)(30)(31)(32)(33). To achieve this, we attempted to identify miRNAs that control PARP expression.…”

“…a reduction in PGC-1a and mitochondrial biogenesis and function in skeletal muscle (33). Similarly, endurance exercise downregulates miR-23 levels and upregulates PGC-1a, along with several downstream targets of PGC1a, including aminolevulinate synthase, CS, and Cyt C mRNAs (32). However, the precise role of miRNAs in HFD-induced skeletal muscle metabolic impairment is unknown.…”

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

“…MiRNAs are ~22 nucleotides long and inhibit translation or promote mRNA degradation by annealing to complementary sequences in the 3´untranslated regions (UTRs) of specific target mRNAs. It is estimated that there are more than 1500 miRNAs encoded by the human genome, roughly equaling the number of transcription factors [117]. The power of miRNAs as regulators of gene expression is also underscored by recent study demonstrating their ability to upregulate translation of specific targets [118].…”