Can activation account for 80% of skeletal muscle energy use during isometric contraction?

Among others, the retinol dehydrogenase Rdh10 catalyzes the rate-limiting reaction that converts retinol into retinoic acid (RA), an autacoid that regulates energy balance and suppresses adiposity. Relative to WT, Rdh10+/- males experienced reduced fatty-acid oxidation, glucose intolerance and insulin resistance. Running endurance decreased 40%. Rdh10+/- females increased reliance on fatty acid oxidation and did not experience glucose intolerance nor insulin resistance. Running endurance improved 2.2-fold. Estrogen increased, revealed by a 40% increase in uterine weight. Because skeletal muscle energy use restricts adiposity and insulin resistance, we assessed the mixed fiber type gastrocnemius muscle (GM) to determine the effects of endogenous RA on muscle metabolism in vivo. RA in Rdh10+/- male GM decreased 38% relative to WT. TAG content increased 1.7-fold. Glut1 mRNA and glucose decreased >30%. Rdh10+/- male GM had impaired electron transport chain activity, and a 60% reduction in fasting ATP. The share of oxidative fibers increased, as did expression of the myogenic transcription factors Myog and Myf5. Centralized nuclei increased 5-fold in fibersindicating muscle malady or repair. In Rdh10+/- female GM, RA decreased only 17%, due to a 1.8-fold increase in the estrogen-induced retinol dehydrogenase, Dhrs9. Rdh10+/- female GM did not amass TAG, increase oxidative fibers, decrease Glut1 mRNA or glucose, nor increase centralized nuclei. Expression of Myog and Myf5 decreased. Electron transport chain activity increased, elevating fasting ATP >3-fold. Thus, small decreases in skeletal muscle RA affect whole body energy use, insulin resistance and adiposity, in part through estrogen-related sexual dimorphic effects on mitochondria function.

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Resolving Shifting Patterns of Muscle Energy Use in Swimming Fish

PLoS ONE ◽

10.1371/journal.pone.0106030 ◽

2014 ◽

Vol 9 (8) ◽

pp. e106030 ◽

Cited By ~ 12

Author(s):

Shannon P. Gerry ◽

David J. Ellerby

Keyword(s):

Energy Use ◽

Muscle Energy ◽

Muscle Energy Use

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Faculty Opinions recommendation of Cross bridges account for only 20% of total ATP consumption during submaximal isometric contraction in mouse fast-twitch skeletal muscle.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1033053.374661 ◽

2006 ◽

Author(s):

Mark Hargreaves

Keyword(s):

Skeletal Muscle ◽

Isometric Contraction ◽

Cross Bridges ◽

Fast Twitch

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Physical deconditioning may be a mechanism for the skeletal muscle energy phosphate metabolism abnormalities in chronic heart failure

American Heart Journal ◽

10.1016/s0002-8703(96)90537-2 ◽

1996 ◽

Vol 131 (3) ◽

pp. 560-566 ◽

Cited By ~ 40

Author(s):

Zukaï Chati ◽

Faïez Zannad ◽

Claude Jeandel ◽

Brigitte Lherbier ◽

Jean-Marie Escanye ◽

...

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Chronic Heart Failure ◽

Phosphate Metabolism ◽

Muscle Energy ◽

Physical Deconditioning

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Regulation of skeletal muscle energy/nutrient-sensing pathways during metabolic adaptation to fasting in healthy humans

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00215.2014 ◽

2014 ◽

Vol 307 (10) ◽

pp. E885-E895 ◽

Cited By ~ 17

Author(s):

Marjolein A. Wijngaarden ◽

Leontine E. H. Bakker ◽

Gerard C. van der Zon ◽

Peter A. C. 't Hoen ◽

Ko Willems van Dijk ◽

...

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Lipid Oxidation ◽

Energy Homeostasis ◽

Nutrient Sensing ◽

Whole Body ◽

Metabolic Adaptation ◽

Protein Kinase Activity ◽

Short Term ◽

Muscle Energy

During fasting, rapid metabolic adaptations are required to maintain energy homeostasis. This occurs by a coordinated regulation of energy/nutrient-sensing pathways leading to transcriptional activation and repression of specific sets of genes. The aim of the study was to investigate how short-term fasting affects whole body energy homeostasis and skeletal muscle energy/nutrient-sensing pathways and transcriptome in humans. For this purpose, 12 young healthy men were studied during a 24-h fast. Whole body glucose/lipid oxidation rates were determined by indirect calorimetry, and blood and skeletal muscle biopsies were collected and analyzed at baseline and after 10 and 24 h of fasting. As expected, fasting induced a time-dependent decrease in plasma insulin and leptin levels, whereas levels of ketone bodies and free fatty acids increased. This was associated with a metabolic shift from glucose toward lipid oxidation. At the molecular level, activation of the protein kinase B (PKB/Akt) and mammalian target of rapamycin pathways was time-dependently reduced in skeletal muscle during fasting, whereas the AMP-activated protein kinase activity remained unaffected. Furthermore, we report some changes in the phosphorylation and/or content of forkhead protein 1, sirtuin 1, and class IIa histone deacetylase 4, suggesting that these pathways might be involved in the transcriptional adaptation to fasting. Finally, transcriptome profiling identified genes that were significantly regulated by fasting in skeletal muscle at both early and late time points. Collectively, our study provides a comprehensive map of the main energy/nutrient-sensing pathways and transcriptomic changes during short-term adaptation to fasting in human skeletal muscle.

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