scholarly journals Atrophy Resistant vs. Atrophy Susceptible Skeletal Muscles: “aRaS” as a Novel Experimental Paradigm to Study the Mechanisms of Human Disuse Atrophy

2021 ◽  
Vol 12 ◽  
Author(s):  
Joseph J. Bass ◽  
Edward J. O. Hardy ◽  
Thomas B. Inns ◽  
Daniel J. Wilkinson ◽  
Mathew Piasecki ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Thickness ◽  
Muscle Volume ◽  
Medial Gastrocnemius ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Disuse Atrophy ◽  
Experimental Paradigm ◽  
Before And After ◽  
Mechanistic Basis

ObjectiveDisuse atrophy (DA) describes inactivity-induced skeletal muscle loss, through incompletely defined mechanisms. An intriguing observation is that individual muscles exhibit differing degrees of atrophy, despite exhibiting similar anatomical function/locations. We aimed to develop an innovative experimental paradigm to investigate Atrophy Resistant tibialis anterior (TA) and Atrophy Susceptible medial gastrocnemius (MG) muscles (aRaS) with a future view of uncovering central mechanisms.MethodSeven healthy young men (22 ± 1 year) underwent 15 days unilateral leg immobilisation (ULI). Participants had a single leg immobilised using a knee brace and air-boot to fix the leg (75° knee flexion) and ankle in place. Dual-energy X-ray absorptiometry (DXA), MRI and ultrasound scans of the lower leg were taken before and after the immobilisation period to determine changes in muscle mass. Techniques were developed for conchotome and microneedle TA/MG muscle biopsies following immobilisation (both limbs), and preliminary fibre typing analyses was conducted.ResultsTA/MG muscles displayed comparable fibre type distribution of predominantly type I fibres (TA 67 ± 7%, MG 63 ± 5%). Following 15 days immobilisation, MG muscle volume (–2.8 ± 1.4%, p < 0.05) and muscle thickness decreased (−12.9 ± 1.6%, p < 0.01), with a positive correlation between changes in muscle volume and thickness (R2 = 0.31, p = 0.038). Importantly, both TA muscle volume and thickness remained unchanged.ConclusionThe use of this unique “aRaS” paradigm provides an effective and convenient means by which to study the mechanistic basis of divergent DA susceptibility in humans, which may facilitate new mechanistic insights, and by extension, mitigation of skeletal muscle atrophy during human DA.

scholarly journals Preclinical Evaluation of a Food-Derived Functional Ingredient to Address Skeletal Muscle Atrophy

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2274
Author(s):  
Roi Cal ◽  
Heidi Davis ◽  
Alish Kerr ◽  
Audrey Wall ◽  
Brendan Molloy ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Murine Model ◽  
The Body ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Disuse Atrophy ◽  
Tnf Α

Skeletal muscle is the metabolic powerhouse of the body, however, dysregulation of the mechanisms involved in skeletal muscle mass maintenance can have devastating effects leading to many metabolic and physiological diseases. The lack of effective solutions makes finding a validated nutritional intervention an urgent unmet medical need. In vitro testing in murine skeletal muscle cells and human macrophages was carried out to determine the effect of a hydrolysate derived from vicia faba (PeptiStrong: NPN_1) against phosphorylated S6, atrophy gene expression, and tumour necrosis factor alpha (TNF-α) secretion, respectively. Finally, the efficacy of NPN_1 on attenuating muscle waste in vivo was assessed in an atrophy murine model. Treatment of NPN_1 significantly increased the phosphorylation of S6, downregulated muscle atrophy related genes, and reduced lipopolysaccharide-induced TNF-α release in vitro. In a disuse atrophy murine model, following 18 days of NPN_1 treatment, mice exhibited a significant attenuation of muscle loss in the soleus muscle and increased the integrated expression of Type I and Type IIa fibres. At the RNA level, a significant upregulation of protein synthesis-related genes was observed in the soleus muscle following NPN_1 treatment. In vitro and preclinical results suggest that NPN_1 is an effective bioactive ingredient with great potential to prolong muscle health.

scholarly journals Immobilization leads to alterations in intracellular phosphagen and creatine transporter content in human skeletal muscle

2020 ◽  
Vol 319 (1) ◽  
pp. C34-C44 ◽  
Author(s):  
Dan Luo ◽  
Sophie Edwards ◽  
Benoit Smeuninx ◽  
James McKendry ◽  
Yusuke Nishimura ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Fiber Type ◽  
Knee Extensor ◽  
Fat Free Mass ◽  
Type I ◽  
Disuse Atrophy ◽  
Cross Sectional ◽  
Creatine Transporter ◽  
Skeletal Muscle Biopsy ◽  
Before And After

The role of dysregulated intracellular creatine (Cr) metabolism in disuse atrophy is unknown. In this study, skeletal muscle biopsy samples were obtained after 7 days of unilateral leg immobilization (IMMOB) and from the nonimmobilized control limb (CTRL) of 15 healthy men (23.1 ± 3.5 yr). Samples were analyzed for fiber type cross-sectional area (CSA) and creatine transporter (CreaT) at the cell membrane periphery (MEM) or intracellular (INT) areas, via immunofluorescence microscopy. Creatine kinase (CK) and AMP-activated protein kinase (AMPK) were determined via immunoblot. Phosphocreatine (PCr), Cr, and ATP were measured via enzymatic analysis. Body composition and maximal isometric knee extensor strength were assessed before and after disuse. Leg strength and fat-free mass were reduced in IMMOB (~32% and 4%, respectively; P < 0.01 for both). Type II fiber CSA was smaller (~12%; P = 0.028) and intramuscular PCr lower (~13%; P = 0.015) in IMMOB vs. CTRL. CreaT protein was greater in type I fibers in both limbs ( P < 0.01). CreaT was greater in IMMOB vs. CTRL ( P < 0.01) and inversely associated with PCr concentration in both limbs ( P < 0.05). MEM CreaT was greater than INT CreaT in type I and II fibers of both limbs (~14% for both; P < 0.01 for both). Type I fiber CreaT tended to be greater in IMMOB vs. CTRL ( P = 0.074). CK was greater and phospho-to-total AMPKThr172 tended to be greater, in IMMOB vs. CTRL ( P = 0.013 and 0.051, respectively). These findings suggest that modulation of intracellular Cr metabolism is an adaptive response to immobilization in young healthy skeletal muscle.

scholarly journals Physiology of a Microgravity Environment Invited Review: Microgravity and skeletal muscle

2000 ◽  
Vol 89 (2) ◽  
pp. 823-839 ◽  
Author(s):  
Robert H. Fitts ◽  
Danny R. Riley ◽  
Jeffrey J. Widrick
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Thin Filament ◽  
Molecular Mechanisms ◽  
Skeletal Muscle Atrophy ◽  
Microgravity Environment ◽  
Type I ◽  
Fiber Types ◽  
Maximal Velocity ◽  
Cross Sectional

Spaceflight (SF) has been shown to cause skeletal muscle atrophy; a loss in force and power; and, in the first few weeks, a preferential atrophy of extensors over flexors. The atrophy primarily results from a reduced protein synthesis that is likely triggered by the removal of the antigravity load. Contractile proteins are lost out of proportion to other cellular proteins, and the actin thin filament is lost disproportionately to the myosin thick filament. The decline in contractile protein explains the decrease in force per cross-sectional area, whereas the thin-filament loss may explain the observed postflight increase in the maximal velocity of shortening in the type I and IIa fiber types. Importantly, the microgravity-induced decline in peak power is partially offset by the increased fiber velocity. Muscle velocity is further increased by the microgravity-induced expression of fast-type myosin isozymes in slow fibers (hybrid I/II fibers) and by the increased expression of fast type II fiber types. SF increases the susceptibility of skeletal muscle to damage, with the actual damage elicited during postflight reloading. Evidence in rats indicates that SF increases fatigability and reduces the capacity for fat oxidation in skeletal muscles. Future studies will be required to establish the cellular and molecular mechanisms of the SF-induced muscle atrophy and functional loss and to develop effective exercise countermeasures.

Skeletal muscle atrophy: disease-induced mechanisms may mask disuse atrophy

2015 ◽  
Vol 36 (6) ◽  
pp. 405-421 ◽  
Author(s):  
C. J. Malavaki ◽  
G. K. Sakkas ◽  
G. I. Mitrou ◽  
A. Kalyva ◽  
I. Stefanidis ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Disuse Atrophy

scholarly journals Imaging skeletal muscle volume, density, and FDG uptake before and after induction therapy for non-small cell lung cancer

2018 ◽  
Vol 73 (5) ◽  
pp. 505.e1-505.e8 ◽  
Author(s):  
M.D. Goncalves ◽  
S. Taylor ◽  
D.F. Halpenny ◽  
E. Schwitzer ◽  
S. Gandelman ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Skeletal Muscle ◽  
Small Cell Lung Cancer ◽  
Induction Therapy ◽  
Cell Lung Cancer ◽  
Volume Density ◽  
Small Cell ◽  
Muscle Volume ◽  
Small Cell Lung ◽  
Before And After

scholarly journals Hyperglycemia Inhibits Recovery From Disuse-Induced Skeletal Muscle Atrophy in Rats

2014 ◽  
pp. 465-474 ◽  
Author(s):  
H. KATAOKA ◽  
J. NAKANO ◽  
Y. MORIMOTO ◽  
Y. HONDA ◽  
J. SAKAMOTO ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Cross Sections ◽  
Serum Insulin ◽  
Recovery Period ◽  
Diabetic Rats ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Ankle Joints ◽  
Gastrocnemius Muscles

The purpose of this study was to evaluate the effects of hyperglycemia on skeletal muscle recovery following disuse-induced muscle atrophy in rats. Wistar rats were grouped as streptozotocin-induced diabetic rats and non-diabetic rats. Both ankle joints of each rat were immobilized to induce atrophy of the gastrocnemius muscles. After two weeks of immobilization and an additional two weeks of recovery, tail blood and gastrocnemius muscles were isolated. Serial cross sections of muscles were stained for myosin ATPase (pH 4.5) and alkaline phosphatase activity. Serum insulin and muscle insulin-like growth factor-1 (IGF-1) levels were also measured. Serum insulin levels were significantly reduced in the diabetic rats compared to the non-diabetic controls. The diameters of type I, IIa, and IIb myofibers and capillary-to-myofiber ratio in the isolated muscle tissue were decreased after immobilization in both treatments. During the recovery period, these parameters were restored in the non-diabetic rats, but not in the diabetic rats. In addition, muscle IGF-1 levels after recovery increased significantly in the non-diabetic rats, but not in the diabetic rats. We conclude that decreased levels of insulin and IGF-1 and impairment of angiogenesis associated with diabetes might be partly responsible for the inhibition of regrowth in diabetic muscle.

scholarly journals Prediction and validation of total and regional skeletal muscle volume using B-mode ultrasonography in Japanese prepubertal children

2015 ◽  
Vol 114 (8) ◽  
pp. 1209-1217 ◽  
Author(s):  
Taishi Midorikawa ◽  
Megumi Ohta ◽  
Yuki Hikihara ◽  
Suguru Torii ◽  
Shizuo Sakamoto
Keyword(s):  
Skeletal Muscle ◽  
Model Development ◽  
Cervical Vertebra ◽  
Muscle Thickness ◽  
Muscle Volume ◽  
Slice Thickness ◽  
Validation Group ◽  
Prediction Equations ◽  
Prepubertal Children ◽  
Development Group

AbstractVery few effective field methods are available for accurate, non-invasive estimation of skeletal muscle volume (SMV) and mass in children. We aimed to develop regression-based prediction equations for SMV, using ultrasonography, in Japanese prepubertal children, and to assess the validity of these equations. In total, 145 healthy Japanese prepubertal children aged 6–12 years were randomly divided into two groups: the model development group (sixty boys, thirty-seven girls) and the validation group (twenty-nine boys, nineteen girls). Reference data in the form of contiguous MRI with 1-cm slice thickness were obtained from the first cervical vertebra to the ankle joints. The SMV was calculated by the summation of digitised cross-sectional areas. Muscle thickness was measured using B-mode ultrasonography at nine sites in different regions. In the model development group, strong, statistically significant correlations were observed between the site-matched SMV (total, arms, trunk, thigh and lower legs) measured by MRI and the muscle thickness×height measures obtained by ultrasonography, for both boys and girls. When these SMV prediction equations were applied to the validation groups, the measured total and regional SMV were also very similar to the values predicted for boys and girls, respectively. With the exception of the trunk region in girls, the Bland–Altman analysis for the validation group did not indicate any bias for either boys or girls. These results suggest that ultrasonography-derived prediction equations for boys and girls are useful for the estimation of total and regional SMV.

AMPK activation is fiber type specific in human skeletal muscle: effects of exercise and short-term exercise training

2009 ◽  
Vol 107 (1) ◽  
pp. 283-289 ◽  
Author(s):  
Robert S. Lee-Young ◽  
Benedict J. Canny ◽  
Damian E. Myers ◽  
Glenn K. McConell
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Human Skeletal Muscle ◽  
Fiber Type ◽  
Type I ◽  
Specific Expression ◽  
Ampk Phosphorylation ◽  
Before And After ◽  
Subunit Expression ◽  
Exercise Induced

AMP-activated protein kinase (AMPK) has been extensively studied in whole muscle biopsy samples of humans, yet the fiber type-specific expression and/or activation of AMPK is unknown. We examined basal and exercise AMPK-α Thr172 phosphorylation and AMPK subunit expression (α1, α2, and γ3) in type I, IIa, and IIx fibers of human skeletal muscle before and after 10 days of exercise training. Before training basal AMPK phosphorylation was greatest in type IIa fibers ( P < 0.05 vs. type I and IIx), while an acute bout of exercise increased AMPK phosphorylation in all fibers ( P < 0.05), with the greatest increase occurring in type IIx fibers. Exercise training significantly increased basal AMPK phosphorylation in all fibers, and the exercise-induced increases were uniformly suppressed compared with pretraining exercise. Expression of AMPK-α1 and -α2 was similar between fibers and was not altered by exercise training. However, AMPK-γ3 was differentially expressed in skeletal muscle fibers (type IIx > type IIa > type I), irrespective of training status. Thus skeletal muscle AMPK phosphorylation and AMPK expression are fiber type specific in humans in the basal state, as well as during exercise. Our findings reveal fiber type-specific differences that have been masked in previous studies examining mixed muscle samples.

scholarly journals Nuclear factor E2-related factor 2 (NRF2) deficiency accelerates fast fibre type transition in soleus muscle during space flight

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Takuto Hayashi ◽  
Takashi Kudo ◽  
Ryo Fujita ◽  
Shin-ichiro Fujita ◽  
Hirona Tsubouchi ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Space Flight ◽  
Skeletal Muscle Atrophy ◽  
Muscle Fibres ◽  
Type I ◽  
Muscle Plasticity ◽  
Type Transition

AbstractMicrogravity induces skeletal muscle atrophy, particularly in the soleus muscle, which is predominantly composed of slow-twitch myofibre (type I) and is sensitive to disuse. Muscle atrophy is commonly known to be associated with increased production of reactive oxygen species. However, the role of NRF2, a master regulator of antioxidative response, in skeletal muscle plasticity during microgravity-induced atrophy, is not known. To investigate the role of NRF2 in skeletal muscle within a microgravity environment, wild-type and Nrf2-knockout (KO) mice were housed in the International Space Station for 31 days. Gene expression and histological analyses demonstrated that, under microgravity conditions, the transition of type I (oxidative) muscle fibres to type IIa (glycolytic) was accelerated in Nrf2-KO mice without affecting skeletal muscle mass. Therefore, our results suggest that NRF2 affects myofibre type transition during space flight.

scholarly journals Standard values for temporal muscle thickness in the Japanese population who undergo brain check-up by magnetic resonance imaging

2021 ◽  
Vol 12 ◽  
pp. 67
Author(s):  
Masahito Katsuki ◽  
Norio Narita ◽  
Keisuke Sasaki ◽  
Yoshimichi Sato ◽  
Yasuhiro Suzuki ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Skeletal Muscle ◽  
Magnetic Resonance ◽  
Muscle Mass ◽  
Reference Values ◽  
Muscle Thickness ◽  
Muscle Volume ◽  
Resonance Imaging ◽  
Temporal Muscle ◽  
Brain Check

Background: Skeletal muscle mass is an important factor for various diseases’ outcomes. The psoas muscle cross-sectional area on the abdominal computed tomography (CT), gait speed, and handgrip strength is used to measure it. However, it is difficult to measure the neurological patients’ muscle mass or function because (1) we do not perform abdominal CT. (2) Such patients have impaired consciousness, gait disturbance, paresis, and need of rest. Temporal muscle thickness (TMT) on magnetic resonance imaging (MRI) is now attractive for skeletal muscle volume indicator, but the reference values are not established. We herein investigated the standard value of the Japanese TMT using the brain check-up database by MRI. Methods: We retrospectively investigated 360 Japanese individuals from two institutions between 2017 and 2019. We measured TMT on the T1-weighted images in the previously reported way. The associations between TMT and other variables were analyzed. Results: TMT of 214 women and 146 men, ranging from 35 to 84 years old, was investigated. TMT ranged from 3.69 to 16.90 mm. Mean TMT values were significantly higher in men compared to women except for the over 70-year-old cohort. TMT was correlated to weight and body mass index in both sexes. Conclusion: This is the first retrospective study on the standard TMT values from the Japanese brain check-up database. Our results were just reference values, but these would be useful for further investigation in other neurosurgical and neurological diseases regarding muscle volume or sarcopenia.

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