scholarly journals Chronic atorvastatin and exercise can partially reverse established skeletal muscle microvasculopathy in metabolic syndrome

2018 ◽  
Vol 315 (4) ◽  
pp. H855-H870 ◽  
Author(s):  
Kent A. Lemaster ◽  
Stephanie J. Frisbee ◽  
Luc Dubois ◽  
Nikolaos Tzemos ◽  
Fan Wu ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Vascular Function ◽  
Microvascular Dysfunction ◽  
Vascular Wall ◽  
Muscle Performance ◽  
Vascular Structure ◽  
Skeletal Muscle Function ◽  
Targeted Interventions ◽  
Wall Stiffness

It has long been known that chronic metabolic disease is associated with a parallel increase in the risk for developing peripheral vascular disease. Although more clinically relevant, our understanding about reversing established vasculopathy is limited compared with our understanding of the mechanisms and development of impaired vascular structure/function under these conditions. Using the 13-wk-old obese Zucker rat (OZR) model of metabolic syndrome, where microvascular dysfunction is sufficiently established to contribute to impaired skeletal muscle function, we imposed a 7-wk intervention of chronic atorvastatin treatment, chronic treadmill exercise, or both. By 20 wk of age, untreated OZRs manifested a diverse vasculopathy that was a central contributor to poor muscle performance, perfusion, and impaired O2 exchange. Atorvastatin or exercise, with the combination being most effective, improved skeletal muscle vascular metabolite profiles (i.e., nitric oxide, PGI2, and thromboxane A2 bioavailability), reactivity, and perfusion distribution at both individual bifurcations and within the entire microvascular network versus responses in untreated OZRs. However, improvements to microvascular structure (i.e., wall mechanics and microvascular density) were less robust. The combination of the above improvements to vascular function with interventions resulted in an improved muscle performance and O2 transport and exchange versus untreated OZRs, especially at moderate metabolic rates (3-Hz twitch contraction). These results suggest that specific interventions can improve specific indexes of function from established vasculopathy, but either this process was incomplete after 7-wk duration or measures of vascular structure are either resistant to reversal or require better-targeted interventions. NEW & NOTEWORTHY We used atorvastatin and/or chronic exercise to reverse established microvasculopathy in skeletal muscle of rats with metabolic syndrome. With established vasculopathy, atorvastatin and exercise had moderate abilities to reverse dysfunction, and the combined application of both was more effective at restoring function. However, increased vascular wall stiffness and reduced microvessel density were more resistant to reversal. Listen to this article’s corresponding podcast at https://ajpheart.podbean.com/e/reversal-of-microvascular-dysfunction/ .

scholarly journals The myotendinous junction marker collagen XXII enables zebrafish postural control learning and optimal swimming performance through its force transmission activity

2021 ◽  
Author(s):  
Marilyne Malbouyres ◽  
Alexandre Guiraud ◽  
Christel Lefrancois ◽  
Melanie Salamito ◽  
Pauline Nauroy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Swimming Performance ◽  
Muscle Performance ◽  
Myotendinous Junction ◽  
Force Transmission ◽  
Skeletal Muscle Function ◽  
Gene Ablation ◽  
Class 1 ◽  
Control Learning ◽  
Degrees Of Severity

Although the myotendinous junction (MTJ) is essential for skeletal muscle integrity, its contribution to skeletal muscle function remains largely unknown. Here, we show that CRISPR-Cas9-mediated gene ablation of the MTJ marker col22a1 in zebrafish identifies two distinctive phenotypic classes: class 1 individuals reach adulthood with no overt muscle phenotype while class 2 display severe movement impairment and eventually dye before metamorphosis. Yet mutants that are unequally affected are all found to display defective force transmission attributed to a loss of ultrastructural integrity of the MTJ and myosepta, though with distinct degrees of severity. The behavior-related consequences of the resulting muscle weakness similarly reveal variable phenotypic expressivity. Movement impairment at the critical stage of swimming postural learning eventually causes class 2 larval death by compromising food intake while intensive exercise is required to uncover a decline in muscle performance in class 1 adults. By confronting MTJ gene expression compensation and structural, functional and behavioral insights of MTJ dysfunction, our work unravels variable expressivity of col22a1 mutant phenotype. This study also underscores COL22A1 as a candidate gene for myopathies associated with dysfunctional force transmission and anticipates a phenotypically heterogeneous disease.

scholarly journals Action of GH on skeletal muscle function: molecular and metabolic mechanisms

2013 ◽  
Vol 52 (1) ◽  
pp. R107-R123 ◽  
Author(s):  
Viral Chikani ◽  
Ken K Y Ho
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
The Elderly ◽  
Energy System ◽  
Muscle Performance ◽  
Whole Body ◽  
Target Tissue ◽  
Dependent Manner ◽  
Skeletal Muscle Function ◽  
Body Protein

Skeletal muscle is a target tissue of GH. Based on its anabolic properties, it is widely accepted that GH enhances muscle performance in sports and muscle function in the elderly. This paper critically reviews information on the effects of GH on muscle function covering structure, protein metabolism, the role of IGF1 mediation, bioenergetics and performance drawn from molecular, cellular and physiological studies on animals and humans. GH increases muscle strength by enhancing muscle mass without affecting contractile force or fibre composition type. GH stimulates whole-body protein accretion with protein synthesis occurring in muscular and extra-muscular sites. The energy required to power muscle function is derived from a continuum of anaerobic and aerobic sources. Molecular and functional studies provide evidence that GH stimulates the anaerobic and suppresses the aerobic energy system, in turn affecting power-based functional measures in a time-dependent manner. GH exerts complex multi-system effects on skeletal muscle function in part mediated by the IGF system.

scholarly journals Dietary Exercise as a Novel Strategy for the Prevention and Treatment of Metabolic Syndrome: Effects on Skeletal Muscle Function

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Wataru Aoi ◽  
Yuji Naito ◽  
Toshikazu Yoshikawa
Keyword(s):  
Skeletal Muscle ◽  
Metabolic Syndrome ◽  
Epidemiological Studies ◽  
Nutrient Metabolism ◽  
Skeletal Muscle Function ◽  
Adequate Diet ◽  
Expression Activity ◽  
Novel Strategy ◽  
Natural Foods ◽  
Visceral Adipose

A sedentary lifestyle can cause metabolic syndrome to develop. Metabolic syndrome is associated with metabolic function in the skeletal muscle, a major consumer of nutrients. Dietary exercise, along with an adequate diet, is reported to be one of the major preventive therapies for metabolic syndrome; exercise improves the metabolic capacity of muscles and prevents the loss of muscle mass. Epidemiological studies have shown that physical activity reduces the risk of various common diseases such as cardiovascular disease, diabetes, and cancer; it also helps in reducing visceral adipose tissue. In addition, laboratory studies have demonstrated the mechanisms underlying the benefits of single-bout and regular exercise. Exercise regulates the expression/activity of proteins associated with metabolic and anabolic signaling in muscle, leading to a change in phenotype. The extent of these changes depends on the intensity, the duration, and the frequency of the exercise. The effect of exercise is also partly due to a decrease in inflammation, which has been shown to be closely related to the development of various diseases. Furthermore, it has been suggested that several phytochemicals contained in natural foods can improve nutrient metabolism and prevent protein degradation in the muscle.

scholarly journals Effects of Statins on Skeletal Muscle: A Perspective for Physical Therapists

2010 ◽  
Vol 90 (10) ◽  
pp. 1530-1542 ◽  
Author(s):  
Stephanie L. Di Stasi ◽  
Toran D. MacLeod ◽  
Joshua D. Winters ◽  
Stuart A. Binder-Macleod
Keyword(s):  
Skeletal Muscle ◽  
Side Effects ◽  
Physical Therapists ◽  
Physical Therapist ◽  
The United States ◽  
Muscle Performance ◽  
Blood Cholesterol ◽  
Lipid Lowering ◽  
Skeletal Muscle Function ◽  
Statin Use

Hyperlipidemia, also known as high blood cholesterol, is a cardiovascular health risk that affects more than one third of adults in the United States. Statins are commonly prescribed and successful lipid-lowering medications that reduce the risks associated with cardiovascular disease. The side effects most commonly associated with statin use involve muscle cramping, soreness, fatigue, weakness, and, in rare cases, rapid muscle breakdown that can lead to death. Often, these side effects can become apparent during or after strenuous bouts of exercise. Although the mechanisms by which statins affect muscle performance are not entirely understood, recent research has identified some common causative factors. As musculoskeletal and exercise specialists, physical therapists have a unique opportunity to identify adverse effects related to statin use. The purposes of this perspective article are: (1) to review the metabolism and mechanisms of actions of statins, (2) to discuss the effects of statins on skeletal muscle function, (3) to detail the clinical presentation of statin-induced myopathies, (4) to outline the testing used to diagnose statin-induced myopathies, and (5) to introduce a role for the physical therapist for the screening and detection of suspected statin-induced skeletal muscle myopathy.

scholarly journals Time-restricted feeding promotes skeletal muscle function in diet- and genetic-induced obesity through shared and unique pathways

2021 ◽  
Author(s):  
Christopher Livelo ◽  
Yiming Guo ◽  
Shweta Varshney ◽  
Farah Abou Daya ◽  
Hiep Le ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Function ◽  
De Novo ◽  
Tca Cycle ◽  
Glycogen Metabolism ◽  
Fruit Fly ◽  
Muscle Performance ◽  
Restricted Feeding ◽  
Skeletal Muscle Function ◽  
Atp Levels

Abstract Obesity caused by genetic predisposition, a lifestyle of calorie-dense diets and/or circadian disruption can result in complications including metabolic syndrome, cardiovascular disease, and compromised muscle function. By employing time-restricted feeding (TRF), where daily feeding was limited to 12 hours during the day, we observed improved skeletal muscle function compared to ad libitum feeding (ALF). This was observed in both diet-induced obesity (DIO) and genetic-induced obesity (GIO) in a Drosophila melanogaster (fruit fly) model. We evaluated the mechanistic basis of TRF-mediated benefits by utilizing muscle transcriptomic data of indirect flight muscle (IFM) followed by genetic validations, cytological and biochemical evidences. Significant upregulation of glycine N methyltransferase (Gnmt), sarcosine dehydrogenase (Sardh), CG5955 and downregulation of diacylglycerol o-acyltransferase 2 (Dgat2) were commonly induced by TRF intervention under both obese conditions. Moreover, genetic inhibition of Gnmt, Sardh and CG5955 leads to skeletal muscle dysfunction, aberrant lipid accumulation and loss of TRF-mediated benefits. However, skeletal muscle-specific knockdown (KD) of Dgat2 retained muscle function during aging, a result that mimics TRF-mediated benefits. Furthermore, de novo purine biosynthesis appeared to be upregulated specifically in the DIO model under TRF which led to increased ATP levels resulting in improved muscle performance. Additionally, genes associated with AMP kinase (AMPK) signaling, glycogen metabolism, glycolysis, tricarboxylic acid (TCA) cycle and electron transport chain (ETC) signaling were specifically upregulated in GIO model under TRF. TRF mediated benefits in GIO via activation of AMPK, which led to increased ATP levels. Altogether, we identify the shared and distinct pathways in the regulation of muscle function under TRF, which may aid further research and alternative therapeutic avenues that focus on combating comorbidities linked with obesity.

scholarly journals Protein Kinase D1 Stimulates MEF2 Activity in Skeletal Muscle and Enhances Muscle Performance

2008 ◽  
Vol 28 (11) ◽  
pp. 3600-3609 ◽  
Author(s):  
Mi-Sung Kim ◽  
Jens Fielitz ◽  
John McAnally ◽  
John M. Shelton ◽  
Douglas D. Lemon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Class Ii ◽  
Muscle Performance ◽  
Type I ◽  
Type Ii ◽  
Muscle Adaptation ◽  
Skeletal Muscle Function ◽  
Protein Kinase D1 ◽  
Slow Twitch

ABSTRACT Skeletal muscle consists of type I and type II myofibers, which exhibit different metabolic and contractile properties. Type I fibers display an oxidative metabolism and are resistant to fatigue, whereas type II fibers are primarily glycolytic and suited for rapid bursts of activity. These properties can be modified by changes in workload, activity, and hormonal stimuli, facilitating muscle adaptation to physiological demand. The MEF2 transcription factor promotes the formation of slow-twitch (type I) muscle fibers in response to activity. MEF2 activity is repressed by class II histone deacetylases (HDACs) and is enhanced by calcium-regulated protein kinases that promote the export of class II HDACs from the nucleus to the cytoplasm. However, the identities of skeletal muscle class II HDAC kinases are not well defined. Here we demonstrate that protein kinase D1 (PKD1), a highly effective class II HDAC kinase, is predominantly expressed in type I myofibers and, when misexpressed in type II myofibers, promotes transformation to a type I, slow-twitch, fatigue-resistant phenotype. Conversely, genetic deletion of PKD1 in type I myofibers increases susceptibility to fatigue. PKD1 cooperates with calcineurin to facilitate slow-twitch-fiber transformation. These findings identify PKD1 as a key regulator of skeletal muscle function and phenotype.

Perfused Skeletal Muscle-An Experimental Preparation for Many Questions¡

2004 ◽  
Vol 29 (2) ◽  
pp. 123-138
Author(s):  
Jack K. Barclay ◽  
Wendell N. Stainsby
Keyword(s):  
Skeletal Muscle ◽  
Vascular Function ◽  
Mammalian Skeletal Muscle ◽  
Skeletal Muscle Function ◽  
Physiological Quality ◽  
Research Questions ◽  
And Control ◽  
High Degree

Perfused mammalian skeletal muscle preparations either in vitro or in situ are one of the options to be considered when planning a physiological research program or project. Such preparations have been and continue to be used to investigate research questions as diverse as skeletal muscle function and metabolism, peripheral vascular function, and an approximation of exercise. When selecting a perfused muscle preparation, both anatomical and physiological organization must be evaluated in the context of the planned experiment. In any experiment, a number of physiologically significant variables can be manipulated, such as the level of flow and the arterial or inflow concentration of a gas or substance to control substrate supply and metabolite removal as well as the stimulation parameters to alter metabolic rate. The choice of blood or an artificial perfusate is of paramount importance because, when compared to blood-perfused preparations, those receiving artificial perfusates show depressed vascular autoregulation among other changes, indicating a decrease in physiological quality. Overall, perfused skeletal muscle preparations can be used to examine many and varied research questions with close to in-vivo quality and a high degree of accuracy and control if blood-perfused. Keywords: choice of preparation, experimentally controllable variables, evaluation of preparations, pressure-flow autoregulation, flow-independent oxygen uptake

scholarly journals Impact of Presymptomatic COVID-19 on Vascular and Skeletal Muscle Function: A Case Study

2021 ◽  
Author(s):  
Joel D. Trinity ◽  
Jesse C. Craig ◽  
Caitlin C. Fermoyle ◽  
Alec I. McKenzie ◽  
Matthew T. Lewis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Symptom Onset ◽  
Muscle Function ◽  
Vascular Function ◽  
Reactive Hyperemia ◽  
Knee Extension ◽  
Skeletal Muscle Function ◽  
The Impact

The impact of COVID-19 has been largely described after symptom development. Although the SARS-CoV-2 virus elevates heart rate (HR) prior to symptom onset, whether this virus evokes other presymptomatic alterations is unknown. This Case Study details the presymptomatic impact of COVID-19 on vascular and skeletal muscle function in a young woman (24yrs, 173.5cm, 89kg, BMI: 29.6kg·m-2). Vascular and skeletal muscle function were assessed as part of a separate study with the first and second visits separated by 2 weeks. On the evening following the second visit, the participant developed a fever and a rapid antigen test confirmed a positive COVID-19 diagnosis. Compared to the first visit, the participant presented with a markedly elevated HR (~ 30 bpm) and lower mean blood pressure (~8 mmHg) at the second visit. Vascular function measured by brachial artery flow-mediated dilation, reactive hyperemia, and passive leg movement were all noticeably attenuated (25-65%) as was leg blood flow during knee extension exercise. Muscle strength was diminished as was ADP stimulated respiration (30%), assessed in vitro, while there was a 25% increase in the apparent Km. Lastly, an elevation in IL-10 was observed prior to symptom onset. Notably, 2.5 months after diagnosis symptoms of fatigue and cough were still present. Together, these findings provide unique insight into the physiological responses immediately prior to COVID-19 symptom onset; they suggest that SARS-CoV-2 negatively impacts vascular and skeletal muscle function prior to the onset of common symptoms and may set the stage for the widespread sequelae observed following COVID-19 diagnosis.

Sign in / Sign up

Export Citation Format

Share Document