scholarly journals A model of exercise-induced changes in metabolism, signaling, and gene expression in skeletal muscle

2021 ◽  
Author(s):  
Ilya R. Akberdin ◽  
Ilya N. Kiselev ◽  
Sergey S. Pintus ◽  
Ruslan N. Sharipov ◽  
Alexander Yu. Vertyshev ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Genetic Regulation ◽  
Muscle Fibres ◽  
Modular Modeling ◽  
Modular Model ◽  
Exercise Induced ◽  
Induced Changes ◽  
Gene Expression Levels ◽  
Original Experimental Data

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.

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 ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Signaling Pathways ◽  
Human Skeletal Muscle ◽  
Genetic Regulation ◽  
Muscle Fibres ◽  
Modular Modeling ◽  
Systematic Understanding ◽  
Exercise Induced ◽  
Induced Changes

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.

scholarly journals Effect of Genistein Supplementation on Exercise-Induced Inflammation and Oxidative Stress in Mice Liver and Skeletal Muscle

Medicina ◽  
2021 ◽  
Vol 57 (10) ◽  
pp. 1028
Author(s):  
Cong Wu ◽  
Siyi Zhou ◽  
Sihui Ma ◽  
Katsuhiko Suzuki
Keyword(s):  
Oxidative Stress ◽  
Gene Expression ◽  
Skeletal Muscle ◽  
Skeletal Muscles ◽  
Protein Carbonyl ◽  
Liver Protein ◽  
Expression Levels ◽  
Exercise Induced ◽  
And Oxidative Stress ◽  
Gene Expression Levels

The purpose of this study was to investigate the influences of oral high-dose genistein (GE) administration on exercise-induced oxidative stress, inflammatory response, tissue damage, and physical performance. Plasma aspartate aminotransferase (AST), alanine aminotransferase (ALT) levels, liver interleukin (IL)-6, IL-1β, superoxide dismutase 1 (SOD1), catalase (CAT), hemeoxygenase-1 (HO-1) gene expression levels and skeletal muscle IL-6, nuclear factor erythroid 2-related factor (Nrf2), and increased immediately after exhaustive exercise. Thiobarbituric acid reactive substance (TBARS) and protein carbonyl (PC) concentrations in plasma and skeletal muscles were not altered by exercise or GE supplementation. Contrary to our expectations, GE supplementation increased liver protein carbonyl concentrations. On the other hand, GE supplementation significantly decreased SOD1, CAT gene expression levels in the liver and Nrf2, and HO-1 gene expression levels in the skeletal muscles. In conclusion, acute exercise was able to induce organ damage, inflammation, and oxidative stress in skeletal muscles and the liver. However, a single dose of GE supplementation before exercise did not lead to favorable antioxidant and anti-inflammatory effects in this study. Moreover, the oxidative stress in the liver was actually aggravated by GE supplementation, slightly, along with the suppression of antioxidant enzyme expression. According to our findings, further studies are needed to use relatively low-dose and long-term GE supplementation to elicit its health-promoting effects.

scholarly journals Repeatability of exercise-induced changes in mRNA expression and technical considerations for qPCR analysis in human skeletal muscle

2019 ◽  
Vol 104 (3) ◽  
pp. 407-420 ◽  
Author(s):  
Hashim Islam ◽  
Brittany A. Edgett ◽  
Jacob T. Bonafiglia ◽  
Talya Shulman ◽  
Andrew Ma ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Human Skeletal Muscle ◽  
Qpcr Analysis ◽  
Exercise Induced ◽  
Induced Changes ◽  
Technical Considerations

scholarly journals Hypoxia preconditioning promotes endurance exercise capacity of mice by activating skeletal muscle Nrf2

2019 ◽  
Vol 127 (5) ◽  
pp. 1267-1277
Author(s):  
Linjia Wang ◽  
Simin Yang ◽  
Lu Yan ◽  
Hao Wei ◽  
Jianxiong Wang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Exercise Capacity ◽  
Treadmill Exercise ◽  
Related Factor ◽  
Nuclear Factor ◽  
Wild Type ◽  
Hypoxia Preconditioning ◽  
Nrf2 Knockout ◽  
Exercise Induced ◽  
Induced Changes

Elite endurance athletes are used to train under hypoxic/high-altitude conditions, which can elicit certain stress responses in skeletal muscle and helps to improve their physical performance. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular redox homeostasis and metabolism in skeletal muscle, playing important roles in adaptation to various stresses. In this study, Nrf2 knockout (KO) and wild-type (WT) mice were preconditioned to 48 h of hypoxia exposure (11.2% oxygen), and the effects of hypoxia preconditioning (HP) on exercise capacity and exercise-induced changes of antioxidant status, energetic metabolism, and mitochondrial adaptation in skeletal muscle were evaluated. Nrf2 knockout (KO) and wild-type (WT) mice were exposed to normoxia or hypoxia for 48 h before taking incremental treadmill exercise to exhaustion under hypoxia. The skeletal muscles were collected immediately after the incremental treadmill exercise to evaluate the impacts of HP and Nrf2 on the exercise-induced changes. The results indicate the absence of Nrf2 did not affect exercise capacity, although the mRNA expression of certain muscular genes involved in antioxidant, glycogen and fatty acid catabolism was decreased in Nrf2 KO mice. However, 48-h HP enhanced exercise capacity in WT mice but not in Nrf2 KO mice, and the exercise capacity of WT mice was significantly higher than that of Nrf2 KO mice. These findings suggest HP promotes exercise capacity of mice with the participation of the Nrf2 signal in skeletal muscle. NEW & NOTEWORTHY Hypoxia preconditioning (HP) activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signal, which was involved in HP-elicited adaptation responses to hypoxia, oxidative, and metabolic stresses in skeletal muscle. On the other hand, Nrf2 deficiency abolished the enhanced exercise capacity after the 48-h HP. Our results indicate that Nrf2 plays an essential role in the exercise capacity-enhancing effect of HP, possibly by modulating muscular antioxidative responses, the mRNA expression of muscular genes involved in glycogen and fatty acid metabolism, as well as mitochondrial biogenesis, and through the cross talk with AMPK and hypoxia-inducible factor-1α signaling.

Dorsomedial hypothalamic corticotropin-releasing factor mediation of exercise-induced anorexia

2005 ◽  
Vol 288 (6) ◽  
pp. R1800-R1805 ◽  
Author(s):  
Maiko Kawaguchi ◽  
Karen A. Scott ◽  
Timothy H. Moran ◽  
Sheng Bi
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Food Intake ◽  
Mrna Expression ◽  
Critical Role ◽  
Voluntary Exercise ◽  
Running Wheel ◽  
Exercise Induced ◽  
Running Wheels ◽  
Induced Changes

Running wheel access and resulting voluntary exercise alter food intake and reduce body weight. The neural mechanisms underlying these effects are unclear. In this study, we first assessed the effects of 7 days of running wheel access on food intake, body weight, and hypothalamic gene expression. We demonstrate that running wheel access significantly decreases food intake and body weight and results in a significant elevation of CRF mRNA expression in the dorsomedial hypothalamus (DMH) but not the paraventricular nucleus. Seven-day running wheel access also results in elevated arcuate nucleus and DMH neuropeptide Y gene expression. To assess a potential role for elevated DMH CRF activity in the activity-induced changes in food intake and body weight, we compared changes in food intake, body weight, and hypothalamic gene expression in rats receiving intracerebroventricular (ICV) CRF antagonist α-helical CRF or vehicle with or without access to running wheels. During a 4-day period of running wheel access, we found that exercise-induced reductions of food intake and body weight were significantly attenuated by ICV injection of the CRF antagonist. The effect on food intake was specific to a blockade of activity-induced changes in meal size. Central CRF antagonist injection further increased DMH CRF mRNA expression in exercised rats. Together, these data suggest that DMH CRF play a critical role in the anorexia resulting from increased voluntary exercise.

scholarly journals Role of PDK1 in skeletal muscle hypertrophy induced by mechanical load

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Naoki Kuramoto ◽  
Kazuhiro Nomura ◽  
Daisuke Kohno ◽  
Tadahiro Kitamura ◽  
Gerard Karsenty ◽  
...  
Keyword(s):  
Gene Expression ◽  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Muscle Hypertrophy ◽  
Mechanical Load ◽  
Static Condition ◽  
Ribosomal Protein S6 ◽  
Pi3k Signaling Pathway ◽  
Induced Changes

AbstractPhosphatidylinositol 3-kinase (PI3K) plays an important role in protein metabolism and cell growth. We here show that mice (M-PDK1KO mice) with skeletal muscle–specific deficiency of 3′-phosphoinositide–dependent kinase 1 (PDK1), a key component of PI3K signaling pathway, manifest a reduced skeletal muscle mass under the static condition as well as impairment of mechanical load–induced muscle hypertrophy. Whereas mechanical load-induced changes in gene expression were not affected, the phosphorylation of ribosomal protein S6 kinase (S6K) and S6 induced by mechanical load was attenuated in skeletal muscle of M-PDK1KO mice, suggesting that PDK1 regulates muscle hypertrophy not through changes in gene expression but through stimulation of kinase cascades such as the S6K-S6 axis, which plays a key role in protein synthesis. Administration of the β2-adrenergic receptor (AR) agonist clenbuterol activated the S6K-S6 axis in skeletal muscle and induced muscle hypertrophy in mice. These effects of clenbuterol were attenuated in M-PDK1KO mice, and mechanical load–induced activation of the S6K-S6 axis and muscle hypertrophy were inhibited in mice with skeletal muscle–specific deficiency of β2-AR. Our results suggest that PDK1 regulates skeletal muscle mass under the static condition and that it contributes to mechanical load–induced muscle hypertrophy, at least in part by mediating signaling from β2-AR.

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