A gene network switch enhances the oxidative capacity of ovine skeletal muscle during late fetal development

It has long been suggested that in skeletal muscle, the ATP-sensitive K+ channel (KATP) channel is important in protecting energy levels and that abolishing its activity causes fiber damage and severely impairs function. The responses to a lack of KATP channel activity vary between muscles and fibers, with the severity of the impairment being the highest in the most glycolytic muscle fibers. Furthermore, glycolytic muscle fibers are also expected to face metabolic stress more often than oxidative ones. The objective of this study was to determine whether the t-tubular KATP channel content differs between muscles and fiber types. KATP channel content was estimated using a semiquantitative immunofluorescence approach by staining cross sections from soleus, extensor digitorum longus (EDL), and flexor digitorum brevis (FDB) muscles with anti-Kir6.2 antibody. Fiber types were determined using serial cross sections stained with specific antimyosin I, IIA, IIB, and IIX antibodies. Changes in Kir6.2 content were compared with changes in CaV1.1 content, as this Ca2+ channel is responsible for triggering Ca2+ release from sarcoplasmic reticulum. The Kir6.2 content was the lowest in the oxidative soleus and the highest in the glycolytic EDL and FDB. At the individual fiber level, the Kir6.2 content within a muscle was in the order of type IIB > IIX > IIA ≥ I. Interestingly, the Kir6.2 content for a given fiber type was significantly different between soleus, EDL, and FDB, and highest in FDB. Correlations of relative fluorescence intensities from the Kir6.2 and CaV1.1 antibodies were significant for all three muscles. However, the variability in content between the three muscles or individual fibers was much greater for Kir6.2 than for CaV1.1. It is suggested that the t-tubular KATP channel content increases as the glycolytic capacity increases and as the oxidative capacity decreases and that the expression of KATP channels may be linked to how often muscles/fibers face metabolic stress.

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Soothing the sleeping giant: improving skeletal muscle oxygen kinetics and exercise intolerance in HFpEF

Journal of Applied Physiology ◽

10.1152/japplphysiol.01127.2014 ◽

2015 ◽

Vol 119 (6) ◽

pp. 734-738 ◽

Cited By ~ 14

Author(s):

Satyam Sarma ◽

Benjamin D. Levine

Keyword(s):

Heart Failure ◽

Skeletal Muscle ◽

Oxygen Consumption ◽

Functional Capacity ◽

Oxidative Capacity ◽

Exercise Intolerance ◽

Aerobic Performance ◽

Muscle Oxygen ◽

Oxygen Kinetics ◽

Patients With Heart Failure

Patients with heart failure with preserved ejection fraction (HFpEF) have similar degrees of exercise intolerance and dyspnea as patients with heart failure with reduced EF (HFrEF). The underlying pathophysiology leading to impaired exertional ability in the HFpEF syndrome is not completely understood, and a growing body of evidence suggests “peripheral,” i.e., noncardiac, factors may play an important role. Changes in skeletal muscle function (decreased muscle mass, capillary density, mitochondrial volume, and phosphorylative capacity) are common findings in HFrEF. While cardiac failure and decreased cardiac reserve account for a large proportion of the decline in oxygen consumption in HFrEF, impaired oxygen diffusion and decreased skeletal muscle oxidative capacity can also hinder aerobic performance, functional capacity and oxygen consumption (V̇o2) kinetics. The impact of skeletal muscle dysfunction and abnormal oxidative capacity may be even more pronounced in HFpEF, a disease predominantly affecting the elderly and women, two demographic groups with a high prevalence of sarcopenia. In this review, we 1) describe the basic concepts of skeletal muscle oxygen kinetics and 2) evaluate evidence suggesting limitations in aerobic performance and functional capacity in HFpEF subjects may, in part, be due to alterations in skeletal muscle oxygen delivery and utilization. Improving oxygen kinetics with specific training regimens may improve exercise efficiency and reduce the tremendous burden imposed by skeletal muscle upon the cardiovascular system.

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Ablation of Protein Kinase CK2β in Skeletal Muscle Fibers Interferes with Their Oxidative Capacity

Pharmaceuticals ◽

10.3390/ph10010013 ◽

2017 ◽

Vol 10 (4) ◽

pp. 13 ◽

Cited By ~ 6

Author(s):

Nane Eiber ◽

Luca Simeone ◽

Said Hashemolhosseini

Keyword(s):

Skeletal Muscle ◽

Protein Kinase ◽

Muscle Fibers ◽

Oxidative Capacity ◽

Skeletal Muscle Fibers

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Interval and Continuous Exercise Training Produce Similar Increases in Skeletal Muscle and Left Ventricle Microvascular Density in Rats

BioMed Research International ◽

10.1155/2013/752817 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 12

Author(s):

Flávio Pereira ◽

Roger de Moraes ◽

Eduardo Tibiriçá ◽

Antonio C. L. Nóbrega

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Left Ventricle ◽

Body Weight Gain ◽

Interval Training ◽

Capillary Density ◽

Oxidative Capacity ◽

Constant Load ◽

Continuous Exercise ◽

Muscle Ct

Interval training (IT), consisting of alternated periods of high and low intensity exercise, has been proposed as a strategy to induce more marked biological adaptations than continuous exercise training (CT). The purpose of this study was to assess the effects of IT and CT with equivalent total energy expenditure on capillary skeletal and cardiac muscles in rats. Wistar rats ran on a treadmill for 30 min per day with no slope (0%), 4 times/week for 13 weeks. CT has constant load of 70% max; IT has cycles of 90% max for 1 min followed by 1 min at 50% max. CT and IT increased endurance and muscle oxidative capacity and attenuated body weight gain to a similar extent (P>0.05). In addition, CT and IT similarly increased functional capillary density of skeletal muscle (CT:30.6±11.7%; IT:28.7±11.9%) and the capillary-to-fiber ratio in skeletal muscle (CT:28.7±14.4%; IT:40.1±17.2%) and in the left ventricle (CT:57.3±53.1%; IT:54.3±40.5%). In conclusion, at equivalent total work volumes, interval exercise training induced similar functional and structural alterations in the microcirculation of skeletal muscle and myocardium in healthy rats compared to continuous exercise training.

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

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00335.2007 ◽

2007 ◽

Vol 293 (5) ◽

pp. R2059-R2069 ◽

Cited By ~ 71

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.

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Regulation of Skeletal Muscle Oxidative Capacity and Insulin Signaling by the Mitochondrial Rhomboid Protease PARL

Cell Metabolism ◽

10.1016/j.cmet.2010.04.004 ◽

2010 ◽

Vol 11 (5) ◽

pp. 412-426 ◽

Cited By ~ 52

Author(s):

Anthony E. Civitarese ◽

Paul S. MacLean ◽

Stacy Carling ◽

Lyndal Kerr-Bayles ◽

Ryan P. McMillan ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Signaling ◽

Oxidative Capacity ◽

Rhomboid Protease ◽

Muscle Oxidative Capacity

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Combined effects of a ketogenic diet and exercise training alter mitochondrial and peroxisomal substrate oxidative capacity in skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00410.2020 ◽

2021 ◽

Author(s):

Tai-Yu Huang ◽

Melissa A. Linden ◽

Scott E. Fuller ◽

Felicia R Goldsmith ◽

Jacob Simon ◽

...

Keyword(s):

Skeletal Muscle ◽

Body Weight ◽

Exercise Training ◽

Fat Mass ◽

Mitochondrial Fission ◽

Critical Role ◽

Oxidative Capacity ◽

Low Fat Diet ◽

Ketogenic Diets ◽

Diet And Exercise

Ketogenic diets (KD) are reported to improve body weight, fat mass, and exercise performance in humans. Unfortunately, most rodent studies have used a low-protein KD, which does not recapitulate diets used by humans. Since skeletal muscle plays a critical role in responding to macronutrient perturbations induced by diet and exercise, the purpose of this study was to test if a normal-protein KD (NPKD) impacts shifts in skeletal muscle substrate oxidative capacity in response to exercise training (ExTr). A high fat, carbohydrate-deficient NPKD (16.1% protein, 83.9% fat, 0% carbohydrate) was given to C57BL/6J male mice for 6 weeks, while controls received a low fat diet with similar protein (15.9% protein, 11.9% fat, 72.2% carbohydrate). On week four of the diet, mice began treadmill training 5 days/week, 60 min/day for 3 weeks. NPKD-fed mice increased body weight and fat mass, while ExTr negated a continued rise in adiposity. ExTr increased intramuscular glycogen, while the NPKD increased intramuscular triglycerides. Neither the NPKD nor ExTr alone altered mitochondrial content; however, in combination, the NPKD-ExTr group showed increases in PGC-1α, as well as markers of mitochondrial fission and fusion. Pyruvate oxidative capacity was unchanged by either intervention, while ExTr increased leucine oxidation in NPKD-fed mice. Lipid metabolism pathways had the most notable changes as the NPKD and ExTr interventions both enhanced mitochondrial and peroxisomal lipid oxidation and many adaptations were additive or synergistic. Overall these results suggest a combination of a NPKD and ExTr induces additive and/or synergistic adaptations in skeletal muscle oxidative capacity.

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Short term intensified training temporarily impairs mitochondrial respiratory capacity in elite endurance athletes

Journal of Applied Physiology ◽

10.1152/japplphysiol.00829.2020 ◽

2021 ◽

Author(s):

Daniele A. Cardinale ◽

Kasper D. Gejl ◽

Kristine Grøsfjeld Petersen ◽

Joachim Nielsen ◽

Niels Ørtenblad ◽

...

Keyword(s):

Skeletal Muscle ◽

Quality Control ◽

Oxidative Capacity ◽

Endurance Athletes ◽

Training Period ◽

Moderate Intensity ◽

Mitochondrial Quality Control ◽

Quality Control Program ◽

Mitochondrial Oxidative Capacity ◽

Mitochondrial Respiratory

Aim: The maintenance of healthy and functional mitochondria is the result of a complex mitochondrial turnover and herein quality-control program which includes both mitochondrial biogenesis and autophagy of mitochondria. The aim of this study was to examine the effect of an intensified training load on skeletal muscle mitochondrial quality control in relation to changes in mitochondrial oxidative capacity, maximal oxygen consumption and performance in highly trained endurance athletes. Methods: 27 elite endurance athletes performed high intensity interval exercise followed by moderate intensity continuous exercise 3 days per week for 4 weeks in addition to their usual volume of training. Mitochondrial oxidative capacity, abundance of mitochondrial proteins, markers of autophagy and antioxidant capacity of skeletal muscle were assessed in skeletal muscle biopsies before and after the intensified training period. Results: The intensified training period increased several autophagy markers suggesting an increased turnover of mitochondrial and cytosolic proteins. In permeabilized muscle fibers, mitochondrial respiration was ~20 % lower after training although some markers of mitochondrial density increased by 5-50%, indicative of a reduced mitochondrial quality by the intensified training intervention. The antioxidative proteins UCP3, ANT1, and SOD2 were increased after training, whereas we found an inactivation of aconitase. In agreement with the lower aconitase activity, the amount of mitochondrial LON protease that selectively degrades oxidized aconitase, was doubled. Conclusion: Together, this suggests that mitochondrial respiratory function is impaired during the initial recovery from a period of intensified endurance training while mitochondrial quality control is slightly activated in highly trained skeletal muscle.

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