scholarly journals A Modular Mathematical Model of Exercise-Induced Changes in Metabolism, Signaling, and Gene Expression in Human Skeletal Muscle

2021 ◽  
Vol 22 (19) ◽  
pp. 10353
Author(s):  
Ilya R. Akberdin ◽  
Ilya N. Kiselev ◽  
Sergey S. Pintus ◽  
Ruslan N. Sharipov ◽  
Alexander Yu Vertyshev ◽  
...  

Skeletal muscle is the principal contributor to exercise-induced changes in human metabolism. Strikingly, although it has been demonstrated that a lot of metabolites accumulating in blood and human skeletal muscle during an exercise activate different signaling pathways and induce the expression of many genes in working muscle fibres, the systematic understanding of signaling–metabolic pathway interrelations with downstream genetic regulation in the skeletal muscle is still elusive. Herein, a physiologically based computational model of skeletal muscle comprising energy metabolism, Ca2+, and AMPK (AMP-dependent protein kinase) signaling pathways and the expression regulation of genes with early and delayed responses was developed based on a modular modeling approach and included 171 differential equations and more than 640 parameters. The integrated modular model validated on diverse including original experimental data and different exercise modes provides a comprehensive in silico platform in order to decipher and track cause–effect relationships between metabolic, signaling, and gene expression levels in skeletal muscle.

2021 ◽  
Author(s):  
Ilya R. Akberdin ◽  
Ilya N. Kiselev ◽  
Sergey S. Pintus ◽  
Ruslan N. Sharipov ◽  
Alexander Yu. Vertyshev ◽  
...  

Skeletal muscle is the principal contributor to exercise-induced changes in human metabolism. Strikingly, although it has been demonstrated that a lot of metabolites accumulating in blood and human skeletal muscle during an exercise activate different signaling pathways and induce expression of many genes in working muscle fibres, the system understanding of signaling-metabolic pathways interrelations with downstream genetic regulation in the skeletal muscle is still elusive. Herein, a physiologically based computational model of skeletal muscle comprising energy metabolism, Ca2+ and AMPK signalling pathways, and expression regulation of genes with early and delayed responses has been developed based on a modular modeling approach. The integrated modular model validated on diverse including original experimental data and different exercise modes provides a comprehensive in silico platform in order to decipher and track cause-effect relationships between metabolic, signaling and gene expression levels in the skeletal muscle.


2019 ◽  
Vol 104 (3) ◽  
pp. 407-420 ◽  
Author(s):  
Hashim Islam ◽  
Brittany A. Edgett ◽  
Jacob T. Bonafiglia ◽  
Talya Shulman ◽  
Andrew Ma ◽  
...  

2005 ◽  
Vol 90 (4) ◽  
pp. 477-486 ◽  
Author(s):  
Milena Penkowa ◽  
Pernille Keller ◽  
Charlotte Keller ◽  
Juan Hidalgo ◽  
Mercedes Giralt ◽  
...  

Author(s):  
Ben Meister ◽  
Christopher Collins ◽  
Mark L McGlynn ◽  
Dustin Russel Slivka

Exercise training increases mitochondrial content in active skeletal muscle. Previous work suggests that mitochondrial-related genes respond favorably to exercise in cold environments. However, the impact of localized tissue cooling is unknown. The purpose is to determine the impact of local muscle cooling during endurance exercise on human skeletal muscle mitochondrial-related gene expression. Twelve subjects (age 28±6 y) cycled at 65% Wpeak. One leg was cooled (C) for 30 minutes before and during exercise with a thermal wrap while the other leg was wrapped but not cooled, room temperature (RT). Muscle biopsies were taken from each VL before and 4 hours post-exercise for the analysis of gene expression. Muscle temperature was lower in C (29.2±0.7°C) than RT (34.1±0.3°C) after pre-cooling for 30 minutes before exercise (p<0.001) and remained lower after exercise in C (36.9±0.5) than RT (38.4±0.2, p<0.001). PGC-1α and NRF1 mRNA expression were lower in C (p=0.012 and p=0.045, respectively) than RT at 4-h post. There were no temperature related differences in other genes (p>0.05). These data suggest that local cooling has an inhibitory effect on exercise-induced PGC-1α and NRF1 expression in human skeletal muscle. Those considering using local cooling during exercise should consider other systemic cooling options. Novelty Bullets • Local cooling has an inhibitory effect on exercise-induced PGC-1α and NRF1 expression in human skeletal muscle. • Local cooling may lead to a less robust exercise stimulus compared to standard conditions.


Author(s):  
I.R. Akberdin ◽  
A.Yu. Vertyshev ◽  
S.S. Pintus ◽  
D.V. Popov ◽  
F.A. Kolpakov

The physiological adaptation to aerobic endurance exercises is provided by activation of signaling pathways in skeletal muscle cells. Training-induced activation of specific signaling pathways results in significant transcriptional responses. Despite the ongoing endeavours to experimentally investigate regulatory mechanisms and signal transduction pathways involved in the contraction-induced adaptation, quantitative contribution of certain signal molecules in expression regulation of genes responsible for intracellular response has not been studied comprehensively yet. The paper presents novel developed model linking Ca2+-dependent signaling pathway and downstream transcription regulation of early and late response genes in human skeletal muscle during exercise. Numerical analysis of the model enabled to reveal crucial steps in this signal transduction pathway for the adaptation and demonstrated the necessity of consideration of additional transcription factors regulating transcription of late response genes in order to adequately reproduce gene expression data that were taken in human vastus lateralis muscle during and after acute cycling exercise.


2011 ◽  
Vol 96 (8) ◽  
pp. 816-816
Author(s):  
Milena Penkowa ◽  
Pernille Keller ◽  
Charlotte Keller ◽  
Juan Hidalgo ◽  
Mercedes Giralt ◽  
...  

2006 ◽  
Vol 99 (2-3) ◽  
pp. 1
Author(s):  
Fabio Ruzzier ◽  
Elena Bandi ◽  
Mihaela Jurdana ◽  
Paola Lorenzon ◽  
Marina Sciancalepore

2004 ◽  
Vol 287 (6) ◽  
pp. E1189-E1194 ◽  
Author(s):  
Christian P. Fischer ◽  
Peter Plomgaard ◽  
Anne K. Hansen ◽  
Henriette Pilegaard ◽  
Bengt Saltin ◽  
...  

Contracting skeletal muscle expresses large amounts of IL-6. Because 1) IL-6 mRNA expression in contracting skeletal muscle is enhanced by low muscle glycogen content, and 2) IL-6 increases lipolysis and oxidation of fatty acids, we hypothesized that regular exercise training, associated with increased levels of resting muscle glycogen and enhanced capacity to oxidize fatty acids, would lead to a less-pronounced increase of skeletal muscle IL-6 mRNA in response to acute exercise. Thus, before and after 10 wk of knee extensor endurance training, skeletal muscle IL-6 mRNA expression was determined in young healthy men ( n = 7) in response to 3 h of dynamic knee extensor exercise, using the same relative workload. Maximal power output, time to exhaustion during submaximal exercise, resting muscle glycogen content, and citrate synthase and 3-hydroxyacyl-CoA dehydrogenase enzyme activity were all significantly enhanced by training. IL-6 mRNA expression in resting skeletal muscle did not change in response to training. However, although absolute workload during acute exercise was 44% higher ( P < 0.05) after the training period, skeletal muscle IL-6 mRNA content increased 76-fold ( P < 0.05) in response to exercise before the training period, but only 8-fold ( P < 0.05, relative to rest and pretraining) in response to exercise after training. Furthermore, the exercise-induced increase of plasma IL-6 ( P < 0.05, pre- and posttraining) was not higher after training despite higher absolute work intensity. In conclusion, the magnitude of the exercise-induced IL-6 mRNA expression in contracting human skeletal muscle was markedly reduced by 10 wk of training.


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