Muscle-enriched microRNA miR-486 decreases in circulation in response to exercise in young men

Abstract

Background: MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional gene regulation. miRNAs are taken in by intracellular exosomes, secreted into circulation, and taken up by other cells, where they regulate cellular functions. We hypothesized that muscle-enriched miRNAs existing in circulation mediate beneficial metabolic responses induced by exercise. To test this hypothesis, we measured changes in muscle-enriched circulating miRNAs (c-miRNAs) in response to acute and chronic aerobic exercise.

Methods: Eleven healthy young men (age, 21.5 ± 4.5 y; height, 168.6 ± 5.3 cm; and body weight, 62.5 ± 9.0 kg) performed a single bout of steady-state cycling exercise at 70% VO2max for 60 min (acute exercise) and cycling training 3 days per week for 4 weeks (chronic exercise). Blood samples were collected from the antecubital vein before and after acute and chronic exercise. RNA was extracted from serum, and the levels of muscle-enriched miRNAs (miR-1, miR-133a, miR-133b, miR-206, miR-208b, miR-486, and miR-499) were measured.

Results: All of these miRNAs, except for miR-486, were found at too low copy numbers at baseline to be compared. miR-486 was significantly decreased by both acute (P = 0.013) and chronic exercise (P = 0.014). In addition, the change ratio of miR-486 due to acute exercise showed a significant negative correlation with VO2max for each subject (R = 0.58, P = 0.038).

Conclusion: The reduction in circulating miR-486 may be associated with metabolic changes during exercise and adaptation induced by training.

Keywords: exercise; maximum oxygen uptake; metabolism; microRNA; skeletal muscle.

Figure 1

Levels of muscle-enriched miRNAs in serum. The levels of muscle-enriched miRNAs (miR-1, miR-133a, miR-133b, miR-206, miR-208b, miR-486, and miR-499) and miR-16 in serum were measured using real-time RT–PCR. miRNAs levels are expressed as a threshold cycle (Ct) detection. Values represent the mean ± standard deviation obtained from 11 subjects.

Figure 2

Changes in circulating miR-486 in response to acute exercise. The level of circulating miR-486 in response to a single bout of exercise was determined. The ratio of the signal for miR-486 to that for miR-16 (A) and cel-miR-39 (B) was calculated for each serum sample. Values represent the mean ± standard deviation obtained from 11 subjects.

Figure 3

Changes in circulating miR-486 in response to chronic exercise. The level of circulating miR-486 in response to 4 weeks of exercise training was determined. The ratio of the signal for miR-486 to that for miR-16 (A) and cel-miR-39 (B) was calculated for each serum sample. Values represent the mean ± standard deviation obtained from 10 subjects.

Figure 4

The relationship between c-miR-486 and VO_2max. Change ratio of miR-486 between before and after a single bout of exercise and VO_2max values were plotted for each of 11 subjects. There was a significant negative correlation between the change ratio of circulating miR-486 (normalized to miR-16) after acute exercise and VO_2max (R = 0.58, P = 0.038).

Figure A1

Time-course change of circulating miR-486 in response to acute exercise. The level of circulating miR-486 was determined before (Pre) and immediately (Post-0 h), 3 h (Post-3 h), 24 h (Post-24 h) after a single bout of exercise. The ratio of the signal for miR-486 to that for miR-16 was calculated for each serum sample. Values represent as the mean ± standard deviation obtained from six subjects. ^*P < 0.05 vs. Pre.

Figure A2

Changes of circulating miRNAs in response to acute exercise. The level of circulating miR-1 (A), miR-133a (B), miR-133b (C), and miR-206 (D) in response to a single bout of exercise was determined. The ratio of the signal for microRNAs to that for miR-16 was calculated for each serum sample. Values represent as the mean ± standard deviation obtained from 11 subjects.