scholarly journals 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 ◽  
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 ◽  
...  

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.

2018 ◽  
Vol 125 (4) ◽  
pp. 999-1010 ◽  
Author(s):  
Nicholas T. Theilen ◽  
Nevena Jeremic ◽  
Gregory J. Weber ◽  
Suresh C. Tyagi

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.


2013 ◽  
Vol 12 (4) ◽  
pp. 898-906 ◽  
Author(s):  
Benjamin T. Wall ◽  
Marlou L. Dirks ◽  
Luc J.C. van Loon

2015 ◽  
Vol 100 (9) ◽  
pp. 1052-1063 ◽  
Author(s):  
Taisuke Ono ◽  
Shingo Takada ◽  
Shintaro Kinugawa ◽  
Hiroyuki Tsutsui

2008 ◽  
Vol 105 (3) ◽  
pp. 902-906 ◽  
Author(s):  
Per A. Tesch ◽  
Ferdinand von Walden ◽  
Thomas Gustafsson ◽  
Richard M. Linnehan ◽  
Todd A. Trappe

Skeletal muscle atrophy is evident after muscle disuse, unloading, or spaceflight and results from decreased protein content as a consequence of decreased protein synthesis, increased protein breakdown or both. At this time, there are essentially no human data describing proteolysis in skeletal muscle undergoing atrophy on Earth or in space, primarily due to lack of valid and accurate methodology. This particular study aimed at assessing the effects of short-term unloading on the muscle contractile proteolysis rate. Eight men were subjected to 72-h unilateral lower limb suspension (ULLS) and intramuscular interstitial levels of the naturally occurring proteolytic tracer 3-methylhistidine (3MH) were measured by means of microdialysis before and on completion of this intervention. The 3MH concentration following 72-h ULLS (2.01 ± 0.22 nmol/ml) was 44% higher ( P < 0.05) than before ULLS (1.56 ± 0.20 nmol/ml). The present experimental model and the employed method determining 3MH in microdialysates present a promising tool for monitoring skeletal muscle proteolysis or metabolism of specific muscles during conditions resulting in atrophy caused by, e.g., disuse and real or simulated microgravity. This study provides evidence that the atrophic processes are evoked rapidly and within 72 h of unloading and suggests that countermeasures should be employed in the early stages of space missions to offset or prevent muscle loss during the period when the rate of muscle atrophy is the highest.


2009 ◽  
Vol 106 (6) ◽  
pp. 2049-2059 ◽  
Author(s):  
Annabelle Z. Caron ◽  
Geneviève Drouin ◽  
Justine Desrosiers ◽  
Frédéric Trensz ◽  
Guillaume Grenier

Skeletal muscle atrophy is a serious concern for patients afflicted by limb restriction due to surgery (e.g., arthrodesis), several articular pathologies (e.g., arthralgia), or simply following cast immobilization. To study the molecular events involved in this immobilization-induced debilitating condition, a convenient mouse model for atrophy is lacking. Here we provide a new immobilization procedure exploiting the normal flexion of the mouse hindlimb using a surgical staple to fix the ventral part of the foot to the distal part of the calf. Histological analysis revealed that our approach induced significant skeletal muscle atrophy by reducing the myofiber size of the tibialis anterior (TA) muscle by 36% compared with the untreated contralateral TA within a few days postimmobilization. Two molecular markers for atrophy, atrogin-1/muscle atrophy F-box (atrogin-1/MAFbx) and muscle ring finger 1 (MuRF-1) mRNAs, were significantly upregulated by 1.9- and 5.9-fold, respectively. Interestingly, our model also revealed the presence of an early inflammatory process during atrophy, characterized by the mRNA upregulation of TNF-α, IL-1, and IL-6 (1.9-, 2.4-, and 3.4-fold, respectively) simultaneously with the upregulation of the common leukocyte marker CD45 (6.1-fold). Moreover, muscle rapidly recovered on remobilization, an event associated with significantly increased levels of uncoupling protein-3 and peroxisome proliferator-activated receptor γ coactivator-1α mRNA, key components of prooxidative muscle metabolism. This model offers unexpected new insights into the molecular events involved in immobilization atrophy.


2007 ◽  
Vol 292 (1) ◽  
pp. C372-C382 ◽  
Author(s):  
Andrew R. Judge ◽  
Alan Koncarevic ◽  
R. Bridge Hunter ◽  
Hsiou-Chi Liou ◽  
Robert W. Jackman ◽  
...  

Skeletal muscle atrophy is associated with a marked and sustained activation of nuclear factor-κB (NF-κB) activity. Previous work showed that p50 is one of the NF-κB family members required for this activation and for muscle atrophy. In this work, we tested whether another NF-κB family member, c-Rel, is required for atrophy. Because endogenous inhibitory factor κBα (IκBα) was activated (i.e., decreased) at 3 and 7 days of muscle disuse (i.e., hindlimb unloading), we also tested if IκBα, which binds and retains Rel proteins in the cytosol, is required for atrophy and intermediates of the atrophy process. To do this, we electrotransferred a dominant negative IκBα (IκBαΔN) in soleus muscles, which were either unloaded or weight bearing. IκBαΔN expression abolished the unloading-induced increase in both NF-κB activation and total ubiquitinated protein. IκBαΔN inhibited unloading-induced fiber atrophy by 40%. The expression of certain genes known to be upregulated with atrophy were significantly inhibited by IκBαΔN expression during unloading, including MAFbx/atrogin-1, Nedd4, IEX, 4E-BP1, FOXO3a, and cathepsin L, suggesting these genes may be targets of NF-κB transcription factors. In contrast, c-Rel was not required for atrophy because the unloading-induced markers of atrophy were the same in c-rel−/− and wild-type mice. Thus IκBα degradation is required for the unloading-induced decrease in fiber size, the increase in protein ubiquitination, activation of NF-κB signaling, and the expression of specific atrophy genes, but c-Rel is not. These data represent a significant advance in our understanding of the role of NF-κB/IκB family members in skeletal muscle atrophy, and they provide new candidate NF-κB target genes for further study.


BMB Reports ◽  
2018 ◽  
Vol 51 (1) ◽  
pp. 39-44 ◽  
Author(s):  
Seung-Eun Song ◽  
Su-Kyung Shin ◽  
So-Young Park ◽  
Il-Seon Hwang ◽  
Seung-Soon Im ◽  
...  

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