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Myogenin regulates exercise capacity and skeletal muscle metabolism in the adult mouse.

Flynn JM, Meadows E, Fiorotto M, Klein WH - PLoS ONE (2010)

Bottom Line: The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear.This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise.The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.

ABSTRACT
Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.

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Enhanced exercise capacity in low- and high-intensity running regimens in Myog-deleted mice.(A) Low intensity exercise. During low-intensity exercise, Myog-deleted mice ran 2.4-fold farther than did wild-type mice (Myog-deleted, n = 4; wild-type n = 6). Blue bar indicates wild-type control values; red bar indicates Myog-deleted values. Error bars represent one standard deviation (P<0.05). (B, C) High-intensity exercise. During 12 consecutive days of high-intensity exercise, Myog-deleted mice ran 1.6-fold farther than did wild-type mice on average (wild-type, n = 7; Myog-deleted, n = 8). Blue line (B) and blue bar (C) indicate wild-type control values; red line (B) and red bar (C) indicate Myog-deleted values. Error bars represent one standard deviation. *P<0.01.
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pone-0013535-g001: Enhanced exercise capacity in low- and high-intensity running regimens in Myog-deleted mice.(A) Low intensity exercise. During low-intensity exercise, Myog-deleted mice ran 2.4-fold farther than did wild-type mice (Myog-deleted, n = 4; wild-type n = 6). Blue bar indicates wild-type control values; red bar indicates Myog-deleted values. Error bars represent one standard deviation (P<0.05). (B, C) High-intensity exercise. During 12 consecutive days of high-intensity exercise, Myog-deleted mice ran 1.6-fold farther than did wild-type mice on average (wild-type, n = 7; Myog-deleted, n = 8). Blue line (B) and blue bar (C) indicate wild-type control values; red line (B) and red bar (C) indicate Myog-deleted values. Error bars represent one standard deviation. *P<0.01.

Mentions: To place stress on skeletal muscle and monitor physical performance, we used involuntary (forced) running on a treadmill and determined exercise capacity under high- and low-intensity running regimens (Fig. S2). We used low-intensity running at 20 m/minute to assay for muscle endurance and oxidative metabolic capacity. The Myog-deleted mice statistically outperformed their littermate controls, showing an overall difference of 144% in the distance run (Fig. 1A). On average, wild-type mice ran 4059 m until exhaustion, whereas Myog-deleted mice ran 9916 m. These results were unanticipated, because we expected the absence of myogenin to negatively affect endurance exercise performance. We then subjected mice to a high-intensity protocol that increased average speed stepwise every 2 minutes until exhaustion (Fig. S2). On average, wild-type mice ran 382 m daily until exhaustion, whereas Myog-deleted mice ran 596 m daily until exhaustion (Fig. 1C). This response was reproducible over 12 days during which Myog-deleted mice ran 56% further than did control mice (Fig. 1B). Myogenin's role in adult skeletal muscle therefore seemed to be different from its role in embryonic and fetal muscle. The enhanced exercise capacity of Myog-deleted mice during both high- and low-intensity running supported the hypothesis that myogenin functions in modulating normal skeletal muscle metabolic activity that had not been detected in previous studies.


Myogenin regulates exercise capacity and skeletal muscle metabolism in the adult mouse.

Flynn JM, Meadows E, Fiorotto M, Klein WH - PLoS ONE (2010)

Enhanced exercise capacity in low- and high-intensity running regimens in Myog-deleted mice.(A) Low intensity exercise. During low-intensity exercise, Myog-deleted mice ran 2.4-fold farther than did wild-type mice (Myog-deleted, n = 4; wild-type n = 6). Blue bar indicates wild-type control values; red bar indicates Myog-deleted values. Error bars represent one standard deviation (P<0.05). (B, C) High-intensity exercise. During 12 consecutive days of high-intensity exercise, Myog-deleted mice ran 1.6-fold farther than did wild-type mice on average (wild-type, n = 7; Myog-deleted, n = 8). Blue line (B) and blue bar (C) indicate wild-type control values; red line (B) and red bar (C) indicate Myog-deleted values. Error bars represent one standard deviation. *P<0.01.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2962629&req=5

pone-0013535-g001: Enhanced exercise capacity in low- and high-intensity running regimens in Myog-deleted mice.(A) Low intensity exercise. During low-intensity exercise, Myog-deleted mice ran 2.4-fold farther than did wild-type mice (Myog-deleted, n = 4; wild-type n = 6). Blue bar indicates wild-type control values; red bar indicates Myog-deleted values. Error bars represent one standard deviation (P<0.05). (B, C) High-intensity exercise. During 12 consecutive days of high-intensity exercise, Myog-deleted mice ran 1.6-fold farther than did wild-type mice on average (wild-type, n = 7; Myog-deleted, n = 8). Blue line (B) and blue bar (C) indicate wild-type control values; red line (B) and red bar (C) indicate Myog-deleted values. Error bars represent one standard deviation. *P<0.01.
Mentions: To place stress on skeletal muscle and monitor physical performance, we used involuntary (forced) running on a treadmill and determined exercise capacity under high- and low-intensity running regimens (Fig. S2). We used low-intensity running at 20 m/minute to assay for muscle endurance and oxidative metabolic capacity. The Myog-deleted mice statistically outperformed their littermate controls, showing an overall difference of 144% in the distance run (Fig. 1A). On average, wild-type mice ran 4059 m until exhaustion, whereas Myog-deleted mice ran 9916 m. These results were unanticipated, because we expected the absence of myogenin to negatively affect endurance exercise performance. We then subjected mice to a high-intensity protocol that increased average speed stepwise every 2 minutes until exhaustion (Fig. S2). On average, wild-type mice ran 382 m daily until exhaustion, whereas Myog-deleted mice ran 596 m daily until exhaustion (Fig. 1C). This response was reproducible over 12 days during which Myog-deleted mice ran 56% further than did control mice (Fig. 1B). Myogenin's role in adult skeletal muscle therefore seemed to be different from its role in embryonic and fetal muscle. The enhanced exercise capacity of Myog-deleted mice during both high- and low-intensity running supported the hypothesis that myogenin functions in modulating normal skeletal muscle metabolic activity that had not been detected in previous studies.

Bottom Line: The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear.This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise.The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Biology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, United States of America.

ABSTRACT
Although skeletal muscle metabolism is a well-studied physiological process, little is known about how it is regulated at the transcriptional level. The myogenic transcription factor myogenin is required for skeletal muscle development during embryonic and fetal life, but myogenin's role in adult skeletal muscle is unclear. We sought to determine myogenin's function in adult muscle metabolism. A Myog conditional allele and Cre-ER transgene were used to delete Myog in adult mice. Mice were analyzed for exercise capacity by involuntary treadmill running. To assess oxidative and glycolytic metabolism, we performed indirect calorimetry, monitored blood glucose and lactate levels, and performed histochemical analyses on muscle fibers. Surprisingly, we found that Myog-deleted mice performed significantly better than controls in high- and low-intensity treadmill running. This enhanced exercise capacity was due to more efficient oxidative metabolism during low- and high-intensity exercise and more efficient glycolytic metabolism during high-intensity exercise. Furthermore, Myog-deleted mice had an enhanced response to long-term voluntary exercise training on running wheels. We identified several candidate genes whose expression was altered in exercise-stressed muscle of mice lacking myogenin. The results suggest that myogenin plays a critical role as a high-level transcriptional regulator to control the energy balance between aerobic and anaerobic metabolism in adult skeletal muscle.

Show MeSH