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 PO-242 Effects of tail suspension on the expression of FNDC5/Irisin protein in rat skeletal muscle

2018 ◽  
Vol 1 (5) ◽  
Author(s):  
Junzhi Sun ◽  
Qiang Jiang
Keyword(s):  
Skeletal Muscle ◽  
Protein Expression ◽  
Muscle Atrophy ◽  
Muscle Fiber ◽  
Soleus Muscle ◽  
Gastrocnemius Muscle ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Tail Suspension ◽  
Gastrocnemius Muscles

Objective Irisin is a myokine secreted by skeletal muscle,and it is a type I membrane protein factor encoded by the protein 5(FNDC5) gene after cleavage and modification of the type III fibronectin component.Dependence of peroxisome proliferator-activated receptor gamma coactivator (PGC-1α).In this study, the potential association between skeletal muscle atrophy and irisin was explored by detecting changes in rat soleus and gastrocnemius irisin-related proteins during unloading. Methods Twenty male 8-week rats were randomly divided into control group C (n=10) and suspension group T (n=10). The tail suspension system (TSS) was used to perform a 2-week tail suspension experiment on the T group. Two weeks after the tail suspension test, the weights of the rats and the wet weights of soleus and gastrocnemius muscles were measured. HE staining was performed under light microscope to observe the changes of muscle fiber area of skeletal muscle in each group. Western-blot was used to detect the protein expression of MURF1, PGC-1α and FNDC5 in soleus muscle and gastrocnemius muscle of each group. Results (1) The soleus muscle and gastrocnemius muscle mass in T group decreased by 28.6% (P<0.05) and 25.8% (P<0.01), respectively. (2) The cross-sectional area of soleus muscle and gastrocnemius muscle fiber in T group decreased by 20.5% (P<0.01) and 25.2% (P<0.05), respectively. (3) The MURF1 protein expression in the gastrocnemius muscle and soleus muscle in the T group was significantly higher than that in the C group (P<0.01). (4) The expression of PGC-1α protein in gastrocnemius muscle and soleus muscle of T group was significantly lower than that in group C (P<0.05). (5) The expression of FNDC5 protein in gastrocnemius muscle and soleus muscle in T group was significantly lower than that in group C (P<0.05). Conclusions After sole tail suspension for two weeks, the soleus and gastrocnemius muscles of the rats were obviously atrophied, and soleus muscle atrophy was more obvious. Skeletal muscle atrophy may be related to increased expression of MURF1. The decrease of FNDC5/Irisin content may be related to the occurrence of skeletal muscle atrophy, and PGC-1α also may be involved in this process.

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.

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 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 Therapeutic Potential of Pterostilbene and Resveratrol on Biomechanic, Biochemical, and Histological Parameters in Streptozotocin-Induced Diabetic Rats

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Bora Tastekin ◽  
Aykut Pelit ◽  
Sait Polat ◽  
Abdullah Tuli ◽  
Leman Sencar ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Blood Glucose ◽  
Therapeutic Potential ◽  
Serum Insulin ◽  
Morphological Structure ◽  
Experimental Period ◽  
Diabetic Rats ◽  
Electron Microscopic ◽  
The Right ◽  
Gastrocnemius Muscles

Aims. The aim of this study was to investigate the effects of pterostilbene (PTS) (trans-3,5-dimethoxy-4′-hydroxystilbene) and resveratrol (RSV) (trans-3,5,4′ trihydroxystilbene) applied at different doses for the treatment of streptozotocin- (STZ-) induced diabetic rats. Materials and Methods. At the end of the 5-week experimental period, the right gastrocnemius muscles of the rats were examined biomechanically, while the left ones were examined histologically. In addition, blood glucose, serum insulin, and malondialdehyde (MDA) levels were analyzed in blood samples taken from the rats. Results. The skeletal muscle isometric contraction forces, which showed a decrease with diabetes, were observed to increase with antioxidant applications. Blood glucose, serum insulin, and MDA levels in diabetic rats approached normal levels after applying PTS. When the electron microscopic images of the rat skeletal muscle were examined, those in the combination treatment group were observed to show a better enhancement in the skeletal muscle morphological structure compared to the other diabetic and treatment groups. Conclusion. According to the findings, we suggest that these antioxidant treatments might have good therapeutic nutraceutical potential for some muscle diseases that coexist with diabetes. These treatments should be comprehensively investigated in the future.

scholarly journals UBE2E1 Is Preferentially Expressed in the Cytoplasm of Slow-Twitch Fibers and Protects Skeletal Muscles from Exacerbated Atrophy upon Dexamethasone Treatment

Cells ◽  
2018 ◽  
Vol 7 (11) ◽  
pp. 214 ◽  
Author(s):  
Cécile Polge ◽  
Julien Aniort ◽  
Andrea Armani ◽  
Agnès Claustre ◽  
Cécile Coudy-Gandilhon ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Muscle Mass ◽  
Muscle Atrophy ◽  
Tibialis Anterior Muscle ◽  
Ubiquitin Proteasome System ◽  
Skeletal Muscle Atrophy ◽  
C2c12 Myotubes ◽  
Type I ◽  
Dexamethasone Treatment ◽  
Sarcomeric Protein

Skeletal muscle mass is reduced during many diseases or physiological situations (disuse, aging), which results in decreased strength and increased mortality. Muscle mass is mainly controlled by the ubiquitin-proteasome system (UPS), involving hundreds of ubiquitinating enzymes (E2s and E3s) that target their dedicated substrates for subsequent degradation. We recently demonstrated that MuRF1, an E3 ubiquitin ligase known to bind to sarcomeric proteins (telethonin, α-actin, myosins) during catabolic situations, interacts with 5 different E2 enzymes and that these E2-MuRF1 couples are able to target telethonin, a small sarcomeric protein, for degradation. Amongst the E2s interacting with MuRF1, E2E1 was peculiar as the presence of the substrate was necessary for optimal MuRF1-E2E1 interaction. In this work, we focused on the putative role of E2E1 during skeletal muscle atrophy. We found that E2E1 expression was restricted to type I and type IIA muscle fibers and was not detectable in type IIB fibers. This strongly suggests that E2E1 targets are fiber-specific and may be strongly linked to the contractile and metabolic properties of the skeletal muscle. However, E2E1 knockdown was not sufficient for preserving the protein content in C2C12 myotubes subjected to a catabolic state (dexamethasone treatment), suggesting that E2E1 is not involved in the development of muscle atrophy. By contrast, E2E1 knockdown aggravated the atrophying process in both catabolic C2C12 myotubes and the Tibialis anterior muscle of mice, suggesting that E2E1 has a protective effect on muscle mass.

Muscle protection during hibernation of Daurian ground squirrels (Spermophilus dauricus): role of atrogin-1, MuRF1, and fiber-type transition

2016 ◽  
Vol 94 (9) ◽  
pp. 619-629 ◽  
Author(s):  
Kai Dang ◽  
Ban Feng ◽  
Yunfang Gao ◽  
Naifei Hu ◽  
Shanfeng Jiang ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Mrna Expression ◽  
Muscle Atrophy ◽  
Hind Limb ◽  
Fiber Type ◽  
Ground Squirrels ◽  
Skeletal Muscle Atrophy ◽  
Type I ◽  
Protective Mechanisms ◽  
Edl Muscle

We investigated the mechanism of protection from skeletal muscle atrophy in the hind limb extensor digitorum longus (EDL) muscle of hibernating Daurian ground squirrels (Spermophilus dauricus Brandt, 1843). The effects of unrestrained hibernation and 14 day hind limb unloading (HLU) on EDL were studied in three seasons (summer, autumn, and winter). Atrogin-1 and MuRF1 mRNA skeletal muscle expression, wet muscle mass, and muscle to body mass ratios were unchanged during hibernation in all three seasons. EDL mass measurements decreased following HLU and atrogin-1 and MuRF1 mRNA expression increased. In summer, atrogin-1 and MuRF1 mRNA expression increased by 85% and 75%, respectively; in autumn, by 95% and 69%, respectively; and in winter, by 91% and 65%, respectively (P < 0.05). In the HLU group, microscopic skeletal muscle changes were present, including a reduction in the percentage of type-I skeletal muscle fibers. Fat storage in Daurian ground squirrels and a shorter photoperiod during hibernation did not affect the protective mechanisms that prevented skeletal muscle atrophy. The results of this study suggest that the stable expression of atrogin-1 and MuRF1 and the transition from fast glycolytic fibers to slow oxidative fibers are associated with a lack of skeletal muscle atrophy in the hibernating Daurian ground squirrel.

scholarly journals HDAC4 Knockdown Alleviates Denervation-Induced Muscle Atrophy by Inhibiting Myogenin-Dependent Atrogene Activation

2021 ◽  
Vol 15 ◽  
Author(s):  
Wenjing Ma ◽  
Yong Cai ◽  
Yuntian Shen ◽  
Xin Chen ◽  
Lilei Zhang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Skeletal Muscle ◽  
Muscle Atrophy ◽  
Muscular Atrophy ◽  
Underlying Mechanism ◽  
Skeletal Muscle Atrophy ◽  
Regulation Mechanism ◽  
Type I ◽  
Muscle Adaptation ◽  
Cross Sectional

Denervation can activate the catabolic pathway in skeletal muscle and lead to progressive skeletal muscle atrophy. At present, there is no effective treatment for muscle atrophy. Histone deacetylase 4 (HDAC4) has recently been found to be closely related to muscle atrophy, but the underlying mechanism of HDAC4 in denervation-induced muscle atrophy have not been described clearly yet. In this study, we found that the expression of HDAC4 increased significantly in denervated skeletal muscle. HDAC4 inhibition can effectively diminish denervation-induced muscle atrophy, reduce the expression of muscle specific E3 ubiquitin ligase (MuRF1 and MAFbx) and autophagy related proteins (Atg7, LC3B, PINK1 and BNIP3), inhibit the transformation of type I fibers to type II fibers, and enhance the expression of SIRT1 and PGC-1 α. Transcriptome sequencing and bioinformatics analysis was performed and suggested that HDAC4 may be involved in denervation-induced muscle atrophy by regulating the response to denervation involved in the regulation of muscle adaptation, cell division, cell cycle, apoptotic process, skeletal muscle atrophy, and cell differentiation. STRING analysis showed that HDAC4 may be involved in the process of muscle atrophy by directly regulating myogenin (MYOG), cell cycle inhibitor p21 (CDKN1A) and salt induced kinase 1 (SIK1). MYOG was significantly increased in denervated skeletal muscle, and MYOG inhibition could significantly alleviate denervation-induced muscle atrophy, accompanied by the decreased MuRF1 and MAFbx. MYOG overexpression could reduce the protective effect of HDAC4 inhibition on denervation-induced muscle atrophy, as evidenced by the decreased muscle mass and cross-sectional area of muscle fibers, and the increased mitophagy. Taken together, HDAC4 inhibition can alleviate denervation-induced muscle atrophy by reducing MYOG expression, and HDAC4 is also directly related to CDKN1A and SIK1 in skeletal muscle, which suggests that HDAC4 inhibitors may be a potential drug for the treatment of neurogenic muscle atrophy. These results not only enrich the molecular regulation mechanism of denervation-induced muscle atrophy, but also provide the experimental basis for HDAC4-MYOG axis as a new target for the prevention and treatment of muscular atrophy.

scholarly journals Protein Supplementation Enhances the Effects of Intermittent Loading on Skeletal Muscles by Activating the mTORC1 Signaling Pathway in a Rat Model of Disuse Atrophy

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2729
Author(s):  
Sho Miyatake ◽  
Kazuo Hino ◽  
Yuko Natsui ◽  
Goro Ebisu ◽  
Satoshi Fujita
Keyword(s):  
Skeletal Muscle ◽  
Ribosomal Protein ◽  
Signaling Pathway ◽  
Muscle Atrophy ◽  
Gastrocnemius Muscle ◽  
Protein Supplementation ◽  
Skeletal Muscle Atrophy ◽  
Ribosomal Protein S6 ◽  
Mtorc1 Signaling ◽  
Gastrocnemius Muscles

Inactivity leads to skeletal muscle atrophy, whereas intermittent loading (IL) during hind limb unloading (HU) attenuates muscle atrophy. However, the combined effects of IL and protein supplementation on disuse muscle atrophy are unclear. Therefore, we investigated the effects of IL and a high-protein oral nutritional supplement (HP) during HU on skeletal muscle mass and protein synthesis/breakdown. Male F344 rats were assigned to the control (CON), 14-day HU (HU), IL during HU (HU + IL), and IL during HU followed by HP administration (2.6 g protein/kg/day; HU + IL + HP) groups. Soleus and gastrocnemius muscles were sampled 30 min after the last IL and HP supplementation. HU decreased relative soleus and gastrocnemius muscle masses. Relative muscle masses and p70 ribosomal protein S6 kinase/ribosomal protein S6 phosphorylation in soleus and gastrocnemius muscles were higher in the HU + IL group than the HU group and further higher in the HU + IL + HP group than the HU + IL group in gastrocnemius muscle. Therefore, protein administration plus IL effectively prevented skeletal muscle atrophy induced by disuse, potentially via enhanced activation of targets downstream of mammalian target of rapamycin complex 1 (mTORC1) signaling pathway.

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