scholarly journals Skeletal Muscle Ribosome and Mitochondrial Biogenesis in Response to Different Exercise Training Modalities

2021 ◽  
Vol 12 ◽  
Author(s):  
Paulo H. C. Mesquita ◽  
Christopher G. Vann ◽  
Stuart M. Phillips ◽  
James McKendry ◽  
Kaelin C. Young ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Mitochondrial Biogenesis ◽  
Ribosome Biogenesis ◽  
Exercise Physiology ◽  
Future Research ◽  
Mitochondrial Dna Copy Number ◽  
Mtorc1 Signaling ◽  
Amp Activated Protein Kinase ◽  
Training Modalities

Skeletal muscle adaptations to resistance and endurance training include increased ribosome and mitochondrial biogenesis, respectively. Such adaptations are believed to contribute to the notable increases in hypertrophy and aerobic capacity observed with each exercise mode. Data from multiple studies suggest the existence of a competition between ribosome and mitochondrial biogenesis, in which the first adaptation is prioritized with resistance training while the latter is prioritized with endurance training. In addition, reports have shown an interference effect when both exercise modes are performed concurrently. This prioritization/interference may be due to the interplay between the 5’ AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin complex 1 (mTORC1) signaling cascades and/or the high skeletal muscle energy requirements for the synthesis and maintenance of cellular organelles. Negative associations between ribosomal DNA and mitochondrial DNA copy number in human blood cells also provide evidence of potential competition in skeletal muscle. However, several lines of evidence suggest that ribosome and mitochondrial biogenesis can occur simultaneously in response to different types of exercise and that the AMPK-mTORC1 interaction is more complex than initially thought. The purpose of this review is to provide in-depth discussions of these topics. We discuss whether a curious competition between mitochondrial and ribosome biogenesis exists and show the available evidence both in favor and against it. Finally, we provide future research avenues in this area of exercise physiology.

HIF-1α in endurance training: suppression of oxidative metabolism

2007 ◽  
Vol 293 (5) ◽  
pp. R2059-R2069 ◽  
Author(s):  
Steven D. Mason ◽  
Helene Rundqvist ◽  
Ioanna Papandreou ◽  
Roger Duh ◽  
Wayne J. McNulty ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Oxidative Metabolism ◽  
Hypoxia Inducible Factor ◽  
Transcriptional Response ◽  
Oxidative Capacity ◽  
Pyruvate Dehydrogenase Kinase ◽  
Amp Activated Protein Kinase ◽  
Training Protocol

During endurance training, exercising skeletal muscle experiences severe and repetitive oxygen stress. The primary transcriptional response factor for acclimation to hypoxic stress is hypoxia-inducible factor-1α (HIF-1α), which upregulates glycolysis and angiogenesis in response to low levels of tissue oxygenation. To examine the role of HIF-1α in endurance training, we have created mice specifically lacking skeletal muscle HIF-1α and subjected them to an endurance training protocol. We found that only wild-type mice improve their oxidative capacity, as measured by the respiratory exchange ratio; surprisingly, we found that HIF-1α null mice have already upregulated this parameter without training. Furthermore, untrained HIF-1α null mice have an increased capillary to fiber ratio and elevated oxidative enzyme activities. These changes correlate with constitutively activated AMP-activated protein kinase in the HIF-1α null muscles. Additionally, HIF-1α null muscles have decreased expression of pyruvate dehydrogenase kinase I, a HIF-1α target that inhibits oxidative metabolism. These data demonstrate that removal of HIF-1α causes an adaptive response in skeletal muscle akin to endurance training and provides evidence for the suppression of mitochondrial biogenesis by HIF-1α in normal tissue.

scholarly journals Effect of Quercetin Treatment on Mitochondrial Biogenesis and Exercise-Induced AMP-Activated Protein Kinase Activation in Rat Skeletal Muscle

Nutrients ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 729 ◽  
Author(s):  
Keiichi Koshinaka ◽  
Asuka Honda ◽  
Hiroyuki Masuda ◽  
Akiko Sato
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Endurance Exercise ◽  
Mitochondrial Biogenesis ◽  
Exercise Performance ◽  
Term Therapy ◽  
High Dose ◽  
Rat Skeletal Muscle ◽  
Amp Activated Protein Kinase ◽  
Quercetin Treatment

The purpose of this study was to evaluate the effect of chronic quercetin treatment on mitochondrial biogenesis, endurance exercise performance and activation levels of AMP-activated protein kinase (AMPK) in rat skeletal muscle. Rats were assigned to a control or quercetin group and were fed for 7 days. Rats treated with quercetin showed no changes in the protein levels of citrate synthase or cytochrome C oxidase IV or those of sirtuin 1, peroxisome proliferator-activated receptor gamma coactivator-1α or phosphorylated AMPK. After endurance swimming exercise, quercetin-treated rats demonstrated no differences in blood and muscle lactate levels or glycogen utilization speed compared to control rats. These results indicate that quercetin treatment does not stimulate mitochondrial biogenesis in skeletal muscle and does not influence metabolism in a way that might enhance endurance exercise capacity. On the other hand, the AMPK phosphorylation level immediately after exercise was significantly lower in quercetin-treated muscles, suggesting that quercetin treatment might provide a disadvantage to muscle adaptation when administered with exercise training. The molecular results of this study indicate that quercetin treatment may not be advantageous for improving endurance exercise performance, at least after high-dose and short-term therapy.

scholarly journals Endurance training lowers ribosome density despite increasing ribosome biogenesis markers in rodent skeletal muscle

2017 ◽  
Vol 10 (1) ◽  
Author(s):  
Matthew A. Romero ◽  
C. Brooks Mobley ◽  
Melissa A. Linden ◽  
Grace Margaret-Eleanor Meers ◽  
Jeffrey S. Martin ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Endurance Training ◽  
Ribosome Biogenesis ◽  
Ribosome Density

scholarly journals Supplementing the maternal diet of rats with butyrate enhances mitochondrial biogenesis in the skeletal muscles of weaned offspring

2017 ◽  
Vol 117 (1) ◽  
pp. 12-20 ◽  
Author(s):  
Yanping Huang ◽  
Shixing Gao ◽  
Guo Jun ◽  
Ruqian Zhao ◽  
Xiaojing Yang
Keyword(s):  
Skeletal Muscle ◽  
Mitochondrial Dna ◽  
Energy Metabolism ◽  
Mitochondrial Biogenesis ◽  
Uncoupling Protein ◽  
Virgin Female ◽  
Female Rats ◽  
Control Group ◽  
Mitochondrial Dna Copy Number ◽  
Protein Expressions

AbstractThe present study aimed to investigate the effects of maternal dietary butyrate supplementation on energy metabolism and mitochondrial biogenesis in offspring skeletal muscle and the possible mediating mechanisms. Virgin female rats were randomly assigned to either control or butyrate diets (1 % butyrate sodium) throughout gestation and lactation. At the end of lactation (21 d), the offspring were killed by exsanguination from the abdominal aorta under anaesthesia. The results showed that maternal butyrate supplementation throughout gestation and lactation did not affect offspring body weight. However, the protein expressions of G-protein-coupled receptors (GPR) 43 and 41 were significantly enhanced in offspring skeletal muscle of the maternal butyrate-supplemented group. The ATP content, most of mitochondrial DNA-encoded gene expressions, the cytochrome c oxidase subunit 1 and 4 protein contents and the mitochondrial DNA copy number were significantly higher in the butyrate group than in the control group. Meanwhile, the protein expressions of type 1 myosin heavy chain, mitochondrial transcription factor A, PPAR-coactivator-1α (PGC-1α) and uncoupling protein 3 were significantly increased in the gastrocnemius muscle of the treatment group compared with the control group. These results indicate for the first time that maternal butyrate supplementation during the gestation and lactation periods influenced energy metabolism and mitochondrial biogenesis through the GPR and PGC-1α pathways in offspring skeletal muscle at weaning.

scholarly journals AMP-Activated Protein Kinase (AMPK) at the Crossroads Between CO2 Retention and Skeletal Muscle Dysfunction in Chronic Obstructive Pulmonary Disease (COPD)

2020 ◽  
Vol 21 (3) ◽  
pp. 955 ◽  
Author(s):  
Joseph Balnis ◽  
Tanner C. Korponay ◽  
Ariel Jaitovich
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Skeletal Muscle ◽  
Pulmonary Disease ◽  
Future Research ◽  
Chronic Obstructive ◽  
Muscle Dysfunction ◽  
Ribosomal Biogenesis ◽  
Obstructive Pulmonary Disease ◽  
Skeletal Muscle Dysfunction ◽  
Amp Activated Protein Kinase

Skeletal muscle dysfunction is a major comorbidity in chronic obstructive pulmonary disease (COPD) and other pulmonary conditions. Chronic CO2 retention, or hypercapnia, also occur in some of these patients. Both muscle dysfunction and hypercapnia associate with higher mortality in these populations. Over the last years, we have established a mechanistic link between hypercapnia and skeletal muscle dysfunction, which is regulated by AMPK and causes depressed anabolism via reduced ribosomal biogenesis and accelerated catabolism via proteasomal degradation. In this review, we discuss the main findings linking AMPK with hypercapnic pulmonary disease both in the lungs and skeletal muscles, and also outline potential avenues for future research in the area based on knowledge gaps and opportunities to expand mechanistic research with translational implications.

Endurance training increases LKB1 and MO25 protein but not AMP-activated protein kinase kinase activity in skeletal muscle

2004 ◽  
Vol 287 (6) ◽  
pp. E1082-E1089 ◽  
Author(s):  
E. B. Taylor ◽  
D. Hurst ◽  
L. J. Greenwood ◽  
J. D. Lamb ◽  
T. D. Cline ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Endurance Training ◽  
Citrate Synthase ◽  
Multiple Roles ◽  
Strongly Correlated ◽  
Muscle Adaptation ◽  
Protein Levels ◽  
Amp Activated Protein Kinase ◽  
Protein Kinase Kinase

LKB1 complexed with MO25 and STRAD has been identified as an AMP-activated protein kinase kinase (AMPKK). We measured relative LKB1 protein abundance and AMPKK activity in liver (LV), heart (HT), soleus (SO), red quadriceps (RQ), and white quadriceps (WQ) from sedentary and endurance-trained rats. We examined trained RQ for altered levels of MO25 protein and LKB1, STRAD, and MO25 mRNA. LKB1 protein levels normalized to HT (1 ± 0.03) were LV (0.50 ± 0.03), SO (0.28 ± 0.02), RQ (0.32 ± 0.01), and WQ (0.12 ± 0.03). AMPKK activities in nanomoles per gram per minute were HT (79 ± 6), LV (220 ± 9), SO (22 ± 2), RQ (29 ± 2), and WQ (42 ± 4). Training increased LKB1 protein in SO, RQ, and WQ ( P < 0.05). LKB1 protein levels after training (%controls) were SO (158 ± 17), RQ (316 ± 17), WQ (191 ± 27), HT (106 ± 2), and LV (104 ± 7). MO25 protein after training (%controls) was 595 ± 71. Training did not affect AMPKK activity. MO25 but not LKB1 or STRAD mRNA increased with training ( P < 0.05). Trained values (%controls) were MO25 (164 ± 22), LKB1 (120 ± 16), and STRAD (112 ± 17). LKB1 protein content strongly correlated ( r = 0.93) with citrate synthase activity in skeletal muscle ( P < 0.05). In conclusion, endurance training markedly increased skeletal muscle LKB1 and MO25 protein without increasing AMPKK activity. LKB1 may be playing multiple roles in skeletal muscle adaptation to endurance training.

Molecular responses to high-intensity interval exerciseThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

2009 ◽  
Vol 34 (3) ◽  
pp. 428-432 ◽  
Author(s):  
Martin Gibala
Keyword(s):  
Protein Kinase ◽  
Endurance Training ◽  
Signaling Pathways ◽  
Mitochondrial Biogenesis ◽  
High Intensity ◽  
Mitogen Activated Protein Kinase ◽  
Interval Exercise ◽  
Mitogen Activated Protein ◽  
High Intensity Interval ◽  
Amp Activated Protein Kinase

From a cell-signaling perspective, short-duration intense muscular work is typically associated with resistance training and linked to pathways that stimulate growth. However, brief repeated sessions of high-intensity interval exercise training (HIT) induce rapid phenotypic changes that resemble traditional endurance training. Given the oxidative phenotype that is rapidly upregulated by HIT, it is plausible that metabolic adaptations to this type of exercise could be mediated in part through signaling pathways normally associated with endurance training. A key controller of oxidative enzyme expression in skeletal muscle is peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional coactivator that serves to coordinate mitochondrial biogenesis. Most studies of acute PGC-1α regulation in humans have used very prolonged exercise interventions; however, it was recently shown that a surprisingly small dose of very intense interval exercise, equivalent to only 2 min of all-out cycling, was sufficient to increase PGC-1α mRNA during recovery. Intense interval exercise has also been shown to acutely increase the activity of signaling pathways linked to PGC-1α and mitochondrial biogenesis, including AMP-activated protein kinase (α1 and α2 subunits) and the p38 mitogen-activated protein kinase. In contrast, signaling pathways linked to muscle growth, including protein kinase B/Akt and downstream targets p70 ribosomal S6 kinase and 4E binding protein 1, are generally unchanged after acute interval exercise. Signaling through AMP-activated protein kinase and p38 mitogen-activated protein kinase to PGC-1α may therefore explain, in part, the metabolic remodeling induced by HIT, including mitochondrial biogenesis and an increased capacity for glucose and fatty acid oxidation.

scholarly journals Metabolic phenotype of skeletal muscle in early critical illness

Thorax ◽  
2018 ◽  
Vol 73 (10) ◽  
pp. 926-935 ◽  
Author(s):  
Zudin A Puthucheary ◽  
Ronan Astin ◽  
Mark J W Mcphail ◽  
Saima Saeed ◽  
Yasmin Pasha ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Critical Illness ◽  
Muscle Mass ◽  
Mitochondrial Biogenesis ◽  
Vastus Lateralis ◽  
Metabolic Phenotype ◽  
Tumour Necrosis Factor Receptor ◽  
Vastus Lateralis Muscle ◽  
Atp Content ◽  
Mitochondrial Dna Copy Number

ObjectivesTo characterise the sketetal muscle metabolic phenotype during early critical illness.MethodsVastus lateralis muscle biopsies and serum samples (days 1 and 7) were obtained from 63 intensive care patients (59% male, 54.7±18.0 years, Acute Physiology and Chronic Health Evaluation II score 23.5±6.5).Measurements and main resultsFrom day 1 to 7, there was a reduction in mitochondrial beta-oxidation enzyme concentrations, mitochondrial biogenesis markers (PGC1α messenger mRNA expression (−27.4CN (95% CI −123.9 to 14.3); n=23; p=0.025) and mitochondrial DNA copy number (−1859CN (IQR −5557–1325); n=35; p=0.032). Intramuscular ATP content was reduced compared tocompared with controls on day 1 (17.7mmol/kg /dry weight (dw) (95% CI 15.3 to 20.0) vs. 21.7 mmol/kg /dw (95% CI 20.4 to 22.9); p<0.001) and decreased over 7 days (−4.8 mmol/kg dw (IQR −8.0–1.2); n=33; p=0.001). In addition, the ratio of phosphorylated:total AMP-K (the bioenergetic sensor) increased (0.52 (IQR −0.09–2.6); n=31; p<0.001). There was an increase in intramuscular phosphocholine (847.2AU (IQR 232.5–1672); n=15; p=0.022), intramuscular tumour necrosis factor receptor 1 (0.66 µg (IQR −0.44–3.33); n=29; p=0.041) and IL-10 (13.6 ng (IQR 3.4–39.0); n=29; p=0.004). Serum adiponectin (10.3 µg (95% CI 6.8 to 13.7); p<0.001) and ghrelin (16.0 ng/mL (IQR −7–100); p=0.028) increased. Network analysis revealed a close and direct relationship between bioenergetic impairment and reduction in muscle mass and between intramuscular inflammation and impaired anabolic signaling. ATP content and muscle mass were unrelated to lipids delivered.ConclusionsDecreased mitochondrial biogenesis and dysregulated lipid oxidation contribute to compromised skeletal muscle bioenergetic status. In addition, intramuscular inflammation was associated with impaired anabolic recovery with lipid delivery observed as bioenergetically inert. Future clinical work will focus on these key areas to ameliorate acute skeletal muscle wasting.Trial registration numberNCT01106300.

5′-AMP-activated protein kinase activity and protein expression are regulated by endurance training in human skeletal muscle

2004 ◽  
Vol 286 (3) ◽  
pp. E411-E417 ◽  
Author(s):  
Christian Frøsig ◽  
Sebastian B. Jørgensen ◽  
D. Grahame Hardie ◽  
Erik A. Richter ◽  
Jørgen F. P. Wojtaszewski
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Exercise Training ◽  
Protein Content ◽  
Endurance Training ◽  
Human Skeletal Muscle ◽  
Protein Kinase Activity ◽  
Local Contraction ◽  
Ampk Activity ◽  
Amp Activated Protein Kinase

The 5′-AMP-activated protein kinase (AMPK) is proposed to be involved in signaling pathways leading to adaptations in skeletal muscle in response to both a single exercise bout and exercise training. This study investigated the effect of endurance training on protein content of catalytic (α1, α2) and regulatory (β1, β2 and γ1, γ2, γ3) subunit isoforms of AMPK as well as on basal AMPK activity in human skeletal muscle. Eight healthy young men performed supervised one-legged knee extensor endurance training for 3 wk. Muscle biopsies were obtained before and 15 h after training in both legs. In response to training the protein content of α1, β2 and γ1 increased in the trained leg by 41, 34, and 26%, respectively (α1 and β2 P < 0.005, γ1 P < 0.05). In contrast, the protein content of the regulatory γ3-isoform decreased by 62% in the trained leg ( P = 0.01), whereas no effect of training was seen for α2, β1, and γ2. AMPK activity associated with the α1- and the α2-isoforms increased in the trained leg by 94 and 49%, respectively (both P < 0.005). In agreement with these observations, phosphorylation of α-AMPK-(Thr172) and of the AMPK target acetyl-CoA carboxylase-β(Ser221) increased by 74 and 180%, respectively (both P < 0.001). Essentially similar results were obtained in four additional subjects studied 55 h after training. This study demonstrates that protein content and basal AMPK activity in human skeletal muscle are highly susceptible to endurance exercise training. Except for the increase in γ1 protein, all observed adaptations to training could be ascribed to local contraction-induced mechanisms, since they did not occur in the contralateral untrained muscle.

scholarly journals Endurance training remodels skeletal muscle phospholipid composition and increases intrinsic mitochondrial respiration in men with Type 2 diabetes

2019 ◽  
Vol 51 (11) ◽  
pp. 586-595 ◽  
Author(s):  
Maria F. Pino ◽  
Natalie A. Stephens ◽  
Alexey M. Eroshkin ◽  
Fanchao Yi ◽  
Andrew Hodges ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Endurance Training ◽  
Mitochondrial Function ◽  
Mitochondrial Respiration ◽  
Phospholipid Composition ◽  
Rna Seq ◽  
Mitochondrial Dna Copy Number

The effects of exercise training on the skeletal muscle (SKM) lipidome and mitochondrial function have not been thoroughly explored in individuals with Type 2 diabetes (T2D). We hypothesize that 10 wk of supervised endurance training improves SKM mitochondrial function and insulin sensitivity that are related to alterations in lipid signatures within SKM of T2D (males n = 8). We employed integrated multi-omics data analyses including ex vivo lipidomics (MS/MS-shotgun) and transcriptomics (RNA-Seq). From biopsies of SKM, tissue and primary myotubes mitochondrial respiration were quantified by high-resolution respirometry. We also performed hyperinsulinemic-euglycemic clamps and blood draws before and after the training. The lipidomics analysis revealed that endurance training (>95% compliance) increased monolysocardiolipin by 68.2% ( P ≤ 0.03), a putative marker of mitochondrial remodeling, and reduced total sphingomyelin by 44.8% ( P ≤ 0.05) and phosphatidylserine by 39.7% ( P ≤ 0.04) and tended to reduce ceramide lipid content by 19.8%. Endurance training also improved intrinsic mitochondrial respiration in SKM of T2D without alterations in mitochondrial DNA copy number or cardiolipin content. RNA-Seq revealed 71 transcripts in SKM of T2D that were differentially regulated. Insulin sensitivity was unaffected, and HbA1c levels moderately increased by 7.3% despite an improvement in cardiorespiratory fitness (V̇o2peak) following the training intervention. In summary, endurance training improves intrinsic and cell-autonomous SKM mitochondrial function and modifies lipid composition in men with T2D independently of alterations in insulin sensitivity and glycemic control.

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