scholarly journals Two Weeks of Smoking Cessation Reverse Cigarette Smoke-Induced Skeletal Muscle Atrophy and Mitochondrial Dysfunction in Mice

2020 ◽  
Author(s):  
Tom Tanjeko Ajime ◽  
Jef Serré ◽  
Rob C I Wüst ◽  
Guy Anselme Mpaka Messa ◽  
Chiel Poffé ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Smoking Cessation ◽  
Mitochondrial Dysfunction ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscles ◽  
Skeletal Muscle Atrophy ◽  
Limb Muscle ◽  
Male Mice ◽  
And Function

Abstract Introduction Apart from its adverse effects on the respiratory system, cigarette smoking also induces skeletal muscle atrophy and dysfunction. Whether short-term smoking cessation can restore muscle mass and function is unknown. We, therefore, studied the impact of 1- and 2-week smoking cessation on skeletal muscles in a mouse model. Methods Male mice were divided into four groups: Air-exposed (14 weeks); cigarette smoke (CS)-exposed (14 weeks); CS-exposed (13 weeks) followed by 1-week cessation; CS-exposed (12 weeks) followed by 2 weeks cessation to examine exercise capacity, physical activity levels, body composition, muscle function, capillarization, mitochondrial function and protein expression in the soleus, plantaris, and diaphragm muscles. Results CS-induced loss of body and muscle mass was significantly improved within 1 week of cessation due to increased lean and fat mass. Mitochondrial respiration and protein levels of the respiratory complexes in the soleus were lower in CS-exposed mice, but similar to control values after 2 weeks of cessation. Exposing isolated soleus muscles to CS extracts reduced mitochondrial respiration that was reversed after removing the extract. While physical activity was reduced in all groups, exercise capacity, limb muscle force, fatigue resistance, fiber size and capillarization, and diaphragm cytoplasmic HIF-1α were unaltered by CS-exposure. However, CS-induced diaphragm atrophy and increased capillary density were not seen after 2 weeks of smoking cessation. Conclusion In male mice, 2 weeks of smoking cessation reversed smoking-induced mitochondrial dysfunction, limb muscle mass loss, and diaphragm muscle atrophy, highlighting immediate benefits of cessation on skeletal muscles. Implications Our study demonstrates that CS-induced skeletal muscle mitochondrial dysfunction and atrophy are significantly improved by 2 weeks of cessation in male mice. We show for the first time that smoking cessation as short as 1 to 2 weeks is associated with immediate beneficial effects on skeletal muscle structure and function with the diaphragm being particularly sensitive to CS-exposure and cessation. This could help motivate smokers to quit smoking as early as possible. The knowledge that smoking cessation has potential positive extrapulmonary effects is particularly relevant for patients referred to rehabilitation programs and those admitted to hospitals suffering from acute or chronic muscle deterioration yet struggling with smoking cessation.

scholarly journals Blockade of Metallothioneins 1 and 2 Increases Skeletal Muscle Mass and Strength

2016 ◽  
Vol 37 (5) ◽  
Author(s):  
Serge Summermatter ◽  
Anais Bouzan ◽  
Eliane Pierrel ◽  
Stefan Melly ◽  
Daniela Stauffer ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Atrophy ◽  
Intracellular Zinc ◽  
Beneficial Effects ◽  
And Function ◽  
Zinc Storage

ABSTRACT Metallothioneins are proteins that are involved in intracellular zinc storage and transport. Their expression levels have been reported to be elevated in several settings of skeletal muscle atrophy. We therefore investigated the effect of metallothionein blockade on skeletal muscle anabolism in vitro and in vivo. We found that concomitant abrogation of metallothioneins 1 and 2 results in activation of the Akt pathway and increases in myotube size, in type IIb fiber hypertrophy, and ultimately in muscle strength. Importantly, the beneficial effects of metallothionein blockade on muscle mass and function was also observed in the setting of glucocorticoid addition, which is a strong atrophy-inducing stimulus. Given the blockade of atrophy and the preservation of strength in atrophy-inducing settings, these results suggest that blockade of metallothioneins 1 and 2 constitutes a promising approach for the treatment of conditions which result in muscle atrophy.

scholarly journals Tail suspension is useful as a sarcopenia model in rats

2021 ◽  
Vol 37 (1) ◽  
Author(s):  
Akira Nemoto ◽  
Toru Goyagi
Keyword(s):  
Skeletal Muscle ◽  
Muscle Contraction ◽  
Experimental Model ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Whole Body ◽  
Skeletal Muscle Atrophy ◽  
Enzyme Linked Immunosorbent Assay ◽  
Control Group ◽  
Simple Method

Abstract Background Sarcopenia promotes skeletal muscle atrophy and exhibits a high mortality rate. Its elucidation is of the highest clinical importance, but an animal experimental model remains controversial. In this study, we investigated a simple method for studying sarcopenia in rats. Results Muscle atrophy was investigated in 24-week-old, male, tail-suspended (TS), Sprague Dawley and spontaneously hypertensive rats (SHR). Age-matched SD rats were used as a control group. The skeletal muscle mass weight, muscle contraction, whole body tension (WBT), cross-sectional area (CSA), and Muscle RING finger-1 (MuRF-1) were assessed. Enzyme-linked immunosorbent assay was used to evaluate the MuRF-1 levels. Two muscles, the extensor digitorum longus and soleus muscles, were selected for representing fast and slow muscles, respectively. All data, except CSA, were analyzed by a one-way analysis of variance, whereas CSA was analyzed using the Kruskal-Wallis test. Muscle mass weight, muscle contraction, WBT, and CSA were significantly lower in the SHR (n = 7) and TS (n = 7) groups than in the control group, whereas MuRF-1 expression was dominant. Conclusions TS and SHR presented sarcopenic phenotypes in terms of muscle mass, muscle contraction and CSA. TS is a useful technique for providing muscle mass atrophy and weakness in an experimental model of sarcopenia in rats.

Role of SIRT2 in regulating the dexamethasone-activated autophagy pathway in skeletal muscle atrophy

2021 ◽  
Author(s):  
Ziqiu HAN ◽  
Cen CHANG ◽  
Weiyi ZHU ◽  
Yanlei ZHANG ◽  
Jing ZHENG ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Skeletal Muscles ◽  
Weight Ratio ◽  
Beclin 1 ◽  
C2c12 Cells ◽  
Skeletal Muscle Atrophy ◽  
Time To Exhaustion ◽  
Endurance Capacity ◽  
Polymerase Chain Reaction Inhibition

The proteolytic autophagy system is involved in a major regulatory pathway in dexamethasone (Dex)-induced muscle atrophy. Sirtuin 2 (SIRT2) is known to participate in modulating autophagy signaling, exerting effects in skeletal muscle atrophy. We aimed to determine the effects of SIRT2 on autophagy in Dex-induced myoatrophy. Mice were randomly divided into the normal, Dex, and sirtinol groups. C2C12 cells were differentiated into myotubes and transfected with short hairpin (sh)-Sirt2-green fluorescent protein (GFP) or Sirt2-GFP lentivirus. To evaluate the mass and function of skeletal muscles, we measured the myofiber cross-sectional area, myotube size, gastrocnemius muscle wet weight/body weight ratio (%), and time-to-exhaustion. The SIRT2, myosin heavy chain (MyHC), LC3, and Beclin-1 expression levels were detected by western blotting and quantitative reverse transcription-polymerase chain reaction. Inhibition of SIRT2 markedly attenuated the muscle mass and endurance capacity. The same phenotype was observed in Sirt2-shRNA-treated myotubes, as evidenced by their decreased size. Conversely, SIRT2 overexpression alleviated Dex-induced myoatrophy in vitro. Moreover, SIRT2 negatively regulated the expression of the LC3b and Beclin-1 in skeletal muscles. These findings suggested that SIRT2 activation protects myotubes against Dex-induced atrophy through the inhibition of the autophagy system; this phenomenon may potentially serve as a target for treating glucocorticoid-induced myopathy.

scholarly journals Expression Levels of Long Non-Coding RNAs Change in Models of Altered Muscle Activity and Muscle Mass

2020 ◽  
Vol 21 (5) ◽  
pp. 1628 ◽  
Author(s):  
Keisuke Hitachi ◽  
Masashi Nakatani ◽  
Shiori Funasaki ◽  
Ikumi Hijikata ◽  
Mizuki Maekawa ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Skeletal Muscle Mass ◽  
Muscle Size ◽  
Skeletal Muscle Atrophy ◽  
Myostatin Gene ◽  
Expression Levels ◽  
Non Coding Rnas

Skeletal muscle is a highly plastic organ that is necessary for homeostasis and health of the human body. The size of skeletal muscle changes in response to intrinsic and extrinsic stimuli. Although protein-coding RNAs including myostatin, NF-κβ, and insulin-like growth factor-1 (IGF-1), have pivotal roles in determining the skeletal muscle mass, the role of long non-coding RNAs (lncRNAs) in the regulation of skeletal muscle mass remains to be elucidated. Here, we performed expression profiling of nine skeletal muscle differentiation-related lncRNAs (DRR, DUM1, linc-MD1, linc-YY1, LncMyod, Neat1, Myoparr, Malat1, and SRA) and three genomic imprinting-related lncRNAs (Gtl2, H19, and IG-DMR) in mouse skeletal muscle. The expression levels of these lncRNAs were examined by quantitative RT-PCR in six skeletal muscle atrophy models (denervation, casting, tail suspension, dexamethasone-administration, cancer cachexia, and fasting) and two skeletal muscle hypertrophy models (mechanical overload and deficiency of the myostatin gene). Cluster analyses of these lncRNA expression levels were successfully used to categorize the muscle atrophy models into two sub-groups. In addition, the expression of Gtl2, IG-DMR, and DUM1 was altered along with changes in the skeletal muscle size. The overview of the expression levels of lncRNAs in multiple muscle atrophy and hypertrophy models provides a novel insight into the role of lncRNAs in determining the skeletal muscle mass.

scholarly journals Stimulation of both estrogen and androgen receptors maintains skeletal muscle mass in gonadectomized male mice but mainly via different pathways

2010 ◽  
Vol 45 (1) ◽  
pp. 45-57 ◽  
Author(s):  
Johan Svensson ◽  
Sofia Movérare-Skrtic ◽  
Sara Windahl ◽  
Charlotte Swanson ◽  
Klara Sjögren
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Skeletal Muscle Mass ◽  
Skeletal Muscle Atrophy ◽  
Gene Transcript ◽  
Male Mice ◽  
Direct Stimulation ◽  
Muscle Weight ◽  
Peripheral Tissues ◽  
Stimulation Of

Testosterone is a major regulator of muscle mass. Little is known whether this is due to a direct stimulation of the androgen receptor (AR) or mediated by aromatization of testosterone to estradiol (E2), the ligand for the estrogen receptors (ERs), in peripheral tissues. In this study, we differentiated between the effects mediated by AR and ER by treating orchidectomized (orx) male mice for 5 weeks with E2 or the non-aromatizable androgen dihydrotestosterone (DHT). Both E2 and DHT increased muscle weight and lean mass, although the effect was less marked after E2 treatment. Studies of underlying mechanisms were performed using gene transcript profiling (microarray and real-time PCR) in skeletal muscle, and they demonstrated that E2 regulated 51 genes and DHT regulated 187 genes, with 13 genes (=25% of E2-regulated genes) being regulated by both treatments. Both E2 and DHT altered the expression of Fbxo32, a gene involved in skeletal muscle atrophy, affected the IGF1 system, and regulated genes involved in angiogenesis and the glutathione metabolic process. Only E2 affected genes that regulate intermediary glucose and lipid metabolism, and only DHT increased the expression of genes involved in synaptic transmission and heme and polyamine biosynthesis. In summary, ER activation by E2 treatment maintains skeletal muscle mass after orx. This effect is less marked than that of AR activation by DHT treatment, which completely prevented the effect of orx on muscle mass and was partly, but not fully, mediated via alternative pathways.

scholarly journals β-Cryptoxanthin Improves p62 Accumulation and Muscle Atrophy in the Soleus Muscle of Senescence-Accelerated Mouse-Prone 1 Mice

Nutrients ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2180
Author(s):  
Mari Noguchi ◽  
Tomoya Kitakaze ◽  
Yasuyuki Kobayashi ◽  
Katsuyuki Mukai ◽  
Naoki Harada ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Soleus Muscle ◽  
Muscle Fibers ◽  
Skeletal Muscle Atrophy ◽  
Related Factor ◽  
Related Factors ◽  
Cross Sectional ◽  
Senescence Accelerated Mouse

We investigated the effects of β-cryptoxanthin on skeletal muscle atrophy in senescence-accelerated mouse-prone 1 (SAMP1) mice. For 15 weeks, SAMP1 mice were intragastrically administered vehicle or β-cryptoxanthin. At 35 weeks of age, the skeletal muscle mass in SAMP1 mice was reduced compared with that in control senescence-accelerated mouse-resistant 1 (SAMR1) mice. β-cryptoxanthin increased muscle mass with an increase in the size of muscle fibers in the soleus muscle of SAMP1 mice. The expressions of autophagy-related factors such as beclin-1, p62, LC3-I, and LC3-II were increased in the soleus muscle of SAMP1 mice; however, β-cryptoxanthin administration inhibited this increase. Unlike in SAMR1 mice, p62 was punctately distributed throughout the cytosol in the soleus muscle fibers of SAMP1 mice; however, β-cryptoxanthin inhibited this punctate distribution. The cross-sectional area of p62-positive fiber was smaller than that of p62-negative fiber, and the ratio of p62-positive fibers to p62-negative fibers was increased in SAMP1 mice. β-cryptoxanthin decreased this ratio in SAMP1 mice. Furthermore, β-cryptoxanthin decreased the autophagy-related factor expression in murine C2C12 myotube. The autophagy inhibitor bafilomycin A1, but not the proteasome inhibitor MG132, inhibited the β-cryptoxanthin-induced decrease in p62 and LC3-II expressions. These results indicate that β-cryptoxanthin inhibits the p62 accumulation in fibers and improves muscle atrophy in the soleus muscle of SAMP1 mice.

scholarly journals MuRF1/TRIM63, Master Regulator of Muscle Mass

2020 ◽  
Vol 21 (18) ◽  
pp. 6663 ◽  
Author(s):  
Dulce Peris-Moreno ◽  
Daniel Taillandier ◽  
Cécile Polge
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Molecular Mechanisms ◽  
Muscle Wasting ◽  
Skeletal Muscle Atrophy ◽  
Cardiac Functions ◽  
Important Player ◽  
Cardiac Muscles ◽  
Inhibitory Molecules

The E3 ubiquitin ligase MuRF1/TRIM63 was identified 20 years ago and suspected to play important roles during skeletal muscle atrophy. Since then, numerous studies have been conducted to decipher the roles, molecular mechanisms and regulation of this enzyme. This revealed that MuRF1 is an important player in the skeletal muscle atrophy process occurring during catabolic states, making MuRF1 a prime candidate for pharmacological treatments against muscle wasting. Indeed, muscle wasting is an associated event of several diseases (e.g., cancer, sepsis, diabetes, renal failure, etc.) and negatively impacts the prognosis of patients, which has stimulated the search for MuRF1 inhibitory molecules. However, studies on MuRF1 cardiac functions revealed that MuRF1 is also cardioprotective, revealing a yin and yang role of MuRF1, being detrimental in skeletal muscle and beneficial in the heart. This review discusses data obtained on MuRF1, both in skeletal and cardiac muscles, over the past 20 years, regarding the structure, the regulation, the location and the different functions identified, and the first inhibitors reported, and aim to draw the picture of what is known about MuRF1. The review also discusses important MuRF1 characteristics to consider for the design of future drugs to maintain skeletal muscle mass in patients with different pathologies.

scholarly journals Exercise preconditioning diminishes skeletal muscle atrophy after hindlimb suspension in mice

2018 ◽  
Vol 125 (4) ◽  
pp. 999-1010 ◽  
Author(s):  
Nicholas T. Theilen ◽  
Nevena Jeremic ◽  
Gregory J. Weber ◽  
Suresh C. Tyagi
Keyword(s):  
Skeletal Muscle ◽  
Exercise Training ◽  
Muscle Atrophy ◽  
Mitochondrial Biogenesis ◽  
Weight Ratio ◽  
Hindlimb Suspension ◽  
Skeletal Muscle Atrophy ◽  
Short Term ◽  
Concurrent Exercise ◽  
And Function

The aim of the present study was to investigate whether short-term, concurrent exercise training before hindlimb suspension (HLS) prevents or diminishes both soleus and gastrocnemius atrophy and to analyze whether changes in mitochondrial molecular markers were associated. Male C57BL/6 mice were assigned to control at 13 ± 1 wk of age, 7-day HLS at 12 ± 1 wk of age (HLS), 2 wk of exercise training before 7-day HLS at 10 ± 1 wk of age (Ex+HLS), and 2 wk of exercise training at 11 ± 1 wk of age (Ex) groups. HLS resulted in a 27.1% and 21.5% decrease in soleus and gastrocnemius muscle weight-to-body weight ratio, respectively. Exercise training before HLS resulted in a 5.6% and 8.1% decrease in soleus and gastrocnemius weight-to-body weight ratio, respectively. Exercise increased mitochondrial biogenesis- and function-associated markers and slow myosin heavy chain (SMHC) expression, and reduced fiber-type transitioning marker myosin heavy chain 4 (Myh4). Ex+HLS revealed decreased reactive oxygen species (ROS) and oxidative stress compared with HLS. Our data indicated the time before an atrophic setting, particularly caused by muscle unloading, may be a useful period to intervene short-term, progressive exercise training to prevent skeletal muscle atrophy and is associated with mitochondrial biogenesis, function, and redox balance. NEW & NOTEWORTHY Mitochondrial dysfunction is associated with disuse-induced skeletal muscle atrophy, whereas exercise is known to increase mitochondrial biogenesis and function. Here we provide evidence of short-term concurrent exercise training before an atrophic event protecting skeletal muscle from atrophy in two separate muscles with different, dominant fiber-types, and we reveal an association with the adaptive changes of mitochondrial molecular markers to exercise.

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