Exercise preconditioning diminishes skeletal muscle atrophy after hindlimb suspension in mice

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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Low-intensity aerobic exercise training: inhibition of skeletal muscle atrophy in high-fat-diet-induced ovariectomized rats

The Journal of Exercise Nutrition and Biochemistry ◽

10.20463/jenb.2017.0022 ◽

2017 ◽

Vol 21 (3) ◽

pp. 19-25 ◽

Cited By ~ 8

Author(s):

Hye Jin Kim ◽

Won Jun Lee

Keyword(s):

Skeletal Muscle ◽

Exercise Training ◽

Aerobic Exercise ◽

Muscle Atrophy ◽

High Fat Diet ◽

Aerobic Exercise Training ◽

Ovariectomized Rats ◽

Skeletal Muscle Atrophy ◽

High Fat ◽

Low Intensity

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Resistance exercise and growth hormone as countermeasures for skeletal muscle atrophy in hindlimb-suspended rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1994.267.2.r365 ◽

1994 ◽

Vol 267 (2) ◽

pp. R365-R371 ◽

Cited By ~ 10

Author(s):

J. K. Linderman ◽

K. L. Gosselink ◽

F. W. Booth ◽

V. R. Mukku ◽

R. E. Grindeland

Keyword(s):

Skeletal Muscle ◽

Growth Hormone ◽

Resistance Exercise ◽

Protein Content ◽

Muscle Atrophy ◽

Myofibrillar Protein ◽

Hindlimb Suspension ◽

Skeletal Muscle Atrophy ◽

Plantar Flexor ◽

Fast Twitch

Unweighting of rat hindlimb muscles results in skeletal muscle atrophy, decreased protein synthesis, and reduced growth hormone (GH) secretion. Resistance exercise (ladder climbing) and GH treatment partially attenuate skeletal muscle atrophy in hypophysectomized hindlimb-suspended rats. It was hypothesized that a combination of multiple bouts of daily resistance exercise and GH (1 mg.kg-1.day-1) would prevent skeletal muscle atrophy in growing nonhypophysectomized hindlimb-suspended rats. Hindlimb suspension decreased the absolute (mg/pair) and relative (mg/100 g body wt) weights of the soleus, a slow-twitch plantar flexor, by 30 and 21%, respectively, and the absolute and relative weights of the gastrocnemius, a predominantly fast-twitch plantar flexor, by 20 and 11%, respectively (P < 0.05). Exercise did not increase soleus mass but attenuated loss of relative wet weight in the gastrocnemius muscles of hindlimb-suspended rats (P < 0.05). Hindlimb suspension decreased gastrocnemius myofibrillar protein content and synthesis (mg/day) by 26 and 64%, respectively (P < 0.05). The combination of exercise and GH attenuated loss of gastrocnemius myofibrillar protein content and synthesis by 70 and 23%, respectively (P < 0.05). Results of the present investigation indicate that a combination of GH and resistance exercise attenuates atrophy of unweighted fast-twitch skeletal muscles.

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Acupuncture ameliorated skeletal muscle atrophy induced by hindlimb suspension and spiral wire immobilization in mice

The FASEB Journal ◽

10.1096/fasebj.26.1_supplement.754.3 ◽

2012 ◽

Vol 26 (S1) ◽

Author(s):

Akiko Onda ◽

Qibin Jiao ◽

Susumu Minamisawa ◽

Toru Fukubayashi

Keyword(s):

Skeletal Muscle ◽

Muscle Atrophy ◽

Hindlimb Suspension ◽

Skeletal Muscle Atrophy

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Effect of short-term hindlimb immobilization on skeletal muscle atrophy and the transcriptome in a low compared with high responder to endurance training model

PLoS ONE ◽

10.1371/journal.pone.0261723 ◽

2022 ◽

Vol 17 (1) ◽

pp. e0261723

Author(s):

Jamie-Lee M. Thompson ◽

Daniel W. D. West ◽

Thomas M. Doering ◽

Boris P. Budiono ◽

Sarah J. Lessard ◽

...

Keyword(s):

Skeletal Muscle ◽

Endurance Training ◽

Muscle Atrophy ◽

Female Rats ◽

Skeletal Muscle Atrophy ◽

Biological Processes ◽

Short Term ◽

Cast Immobilization ◽

Protein Ubiquitination ◽

Differential Gene

Skeletal muscle atrophy is a physiological response to disuse, aging, and disease. We compared changes in muscle mass and the transcriptome profile after short-term immobilization in a divergent model of high and low responders to endurance training to identify biological processes associated with the early atrophy response. Female rats selectively bred for high response to endurance training (HRT) and low response to endurance training (LRT; n = 6/group; generation 19) underwent 3 day hindlimb cast immobilization to compare atrophy of plantaris and soleus muscles with line-matched controls (n = 6/group). RNA sequencing was utilized to identify Gene Ontology Biological Processes with differential gene set enrichment. Aerobic training performed prior to the intervention showed HRT improved running distance (+60.6 ± 29.6%), while LRT were unchanged (-0.3 ± 13.3%). Soleus atrophy was greater in LRT vs. HRT (-9.0 ±8.8 vs. 6.2 ±8.2%; P<0.05) and there was a similar trend in plantaris (-16.4 ±5.6% vs. -8.5 ±7.4%; P = 0.064). A total of 140 and 118 biological processes were differentially enriched in plantaris and soleus muscles, respectively. Soleus muscle exhibited divergent LRT and HRT responses in processes including autophagy and immune response. In plantaris, processes associated with protein ubiquitination, as well as the atrogenes (Trim63 and Fbxo32), were more positively enriched in LRT. Overall, LRT demonstrate exacerbated atrophy compared to HRT, associated with differential gene enrichments of biological processes. This indicates that genetic factors that result in divergent adaptations to endurance exercise, may also regulate biological processes associated with short-term muscle unloading.

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

Biochemistry and Cell Biology ◽

10.1139/bcb-2020-0445 ◽

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.

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

Nicotine & Tobacco Research ◽

10.1093/ntr/ntaa016 ◽

2020 ◽

Cited By ~ 2

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.

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