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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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Blood metabolite values in wild-type and Myog-deleted mice after low-intensity exercise.(A) Blood lactate levels. Blood lactate levels in Myog-deleted mice were similar to those for wild-type mice before and after low-intensity exercise (Myog-deleted, 4.2 mM; wild-type, 4.5 mM). Blue bars indicate wild-type control values; red bars indicate Myog-deleted values. Error bars represent one standard deviation. (B) Blood glucose levels. Myog-deleted mice have further reduced blood glucose levels after low-intensity running. Blood glucose levels in Myog-deleted mice are similar to those for wild-type mice prior to low-intensity exercise (149 mg/dL). After low-intensity exercise exhaustion, blood glucose levels were reduced 78% in Myog-deleted mice compared with 46% for wild-type controls (Myog-deleted, 33 mg/dL; wild-type, 80 mg/dL). Blue bars indicate wild-type control values; red bars indicate Myog-deleted values. Error bars represent one standard deviation. (Myog-deleted, n = 6; wild-type, n = 6) *P<0.05.
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pone-0013535-g002: Blood metabolite values in wild-type and Myog-deleted mice after low-intensity exercise.(A) Blood lactate levels. Blood lactate levels in Myog-deleted mice were similar to those for wild-type mice before and after low-intensity exercise (Myog-deleted, 4.2 mM; wild-type, 4.5 mM). Blue bars indicate wild-type control values; red bars indicate Myog-deleted values. Error bars represent one standard deviation. (B) Blood glucose levels. Myog-deleted mice have further reduced blood glucose levels after low-intensity running. Blood glucose levels in Myog-deleted mice are similar to those for wild-type mice prior to low-intensity exercise (149 mg/dL). After low-intensity exercise exhaustion, blood glucose levels were reduced 78% in Myog-deleted mice compared with 46% for wild-type controls (Myog-deleted, 33 mg/dL; wild-type, 80 mg/dL). Blue bars indicate wild-type control values; red bars indicate Myog-deleted values. Error bars represent one standard deviation. (Myog-deleted, n = 6; wild-type, n = 6) *P<0.05.

Mentions: In both Myog-deleted mice and controls, blood lactate concentrations showed no significant change after running to exhaustion at low-intensity, (Fig. 2A). These results were consistent with low intensity exercise and normal oxidative metabolism. After low-intensity running, glucose levels were lower in both genotypes compared with pre-exercise glucose levels, as would be expected, but Myog-deleted mice had significantly lower blood glucose concentrations than did wild-type mice (Fig. 2B). The results indicated that glucose was being used preferentially in Myog-deleted mice during low-intensity exercise and suggested that Myog-deleted mice were inherently more efficient in utilizing oxidative metabolism than were wild-type mice.


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

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

Blood metabolite values in wild-type and Myog-deleted mice after low-intensity exercise.(A) Blood lactate levels. Blood lactate levels in Myog-deleted mice were similar to those for wild-type mice before and after low-intensity exercise (Myog-deleted, 4.2 mM; wild-type, 4.5 mM). Blue bars indicate wild-type control values; red bars indicate Myog-deleted values. Error bars represent one standard deviation. (B) Blood glucose levels. Myog-deleted mice have further reduced blood glucose levels after low-intensity running. Blood glucose levels in Myog-deleted mice are similar to those for wild-type mice prior to low-intensity exercise (149 mg/dL). After low-intensity exercise exhaustion, blood glucose levels were reduced 78% in Myog-deleted mice compared with 46% for wild-type controls (Myog-deleted, 33 mg/dL; wild-type, 80 mg/dL). Blue bars indicate wild-type control values; red bars indicate Myog-deleted values. Error bars represent one standard deviation. (Myog-deleted, n = 6; wild-type, n = 6) *P<0.05.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2962629&req=5

pone-0013535-g002: Blood metabolite values in wild-type and Myog-deleted mice after low-intensity exercise.(A) Blood lactate levels. Blood lactate levels in Myog-deleted mice were similar to those for wild-type mice before and after low-intensity exercise (Myog-deleted, 4.2 mM; wild-type, 4.5 mM). Blue bars indicate wild-type control values; red bars indicate Myog-deleted values. Error bars represent one standard deviation. (B) Blood glucose levels. Myog-deleted mice have further reduced blood glucose levels after low-intensity running. Blood glucose levels in Myog-deleted mice are similar to those for wild-type mice prior to low-intensity exercise (149 mg/dL). After low-intensity exercise exhaustion, blood glucose levels were reduced 78% in Myog-deleted mice compared with 46% for wild-type controls (Myog-deleted, 33 mg/dL; wild-type, 80 mg/dL). Blue bars indicate wild-type control values; red bars indicate Myog-deleted values. Error bars represent one standard deviation. (Myog-deleted, n = 6; wild-type, n = 6) *P<0.05.
Mentions: In both Myog-deleted mice and controls, blood lactate concentrations showed no significant change after running to exhaustion at low-intensity, (Fig. 2A). These results were consistent with low intensity exercise and normal oxidative metabolism. After low-intensity running, glucose levels were lower in both genotypes compared with pre-exercise glucose levels, as would be expected, but Myog-deleted mice had significantly lower blood glucose concentrations than did wild-type mice (Fig. 2B). The results indicated that glucose was being used preferentially in Myog-deleted mice during low-intensity exercise and suggested that Myog-deleted mice were inherently more efficient in utilizing oxidative metabolism than were wild-type mice.

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
Related in: MedlinePlus