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Molecular Medicine Reports May 2022Hyperglycemia occurs due to a defect in insulin secretion or impaired biological functions, or both. The long‑term hyperglycemia during diabetes causes chronic damage...
Hyperglycemia occurs due to a defect in insulin secretion or impaired biological functions, or both. The long‑term hyperglycemia during diabetes causes chronic damage and dysfunction of various tissues. Whole body vibration (WBV) has significant effects on lipid and glucose metabolism and endocrine and motor systems. In order to explore the effects of WBV on skeletal muscle, mice trained for 12 weeks with WBV (15 Hz, 30 min) were used as experimental subjects and their skeletal muscle morphology under the pathological state of diabetes was observed. In addition, the blood lipids, blood glucose, gastrocnemius muscle glycogen and mRNA and protein levels of autophagy and glucose metabolism biomarkers were compared among the three groups of mice via western blot and RT‑qPCR. The results showed that WBV can significantly reshape skeletal muscle morphology and upregulate high density lipoprotein. The expression of glucose‑6‑phosphatase (G6P), Beclin1 and Atg7 in the gastrocnemius muscle of the WBV group was significantly increased. Therefore, it can be concluded that WBV promotes skeletal muscle remodeling in diabetic mice. The present study confirmed that WBV can attenuate the development of diabetes melitus (DM) and lead to lower level low density lipoprotein in the blood. In addition, G6P level plays an important role in WBV‑treated DM model and may be used to monitor the effect of WBV in patients. The findings of the present study may provide a new molecular basis for WBV to play a therapeutic role in the treatment of diabetes and may have potential clinical applications in the future.
Topics: Animals; Autophagy; Diabetes Mellitus, Experimental; Energy Metabolism; Humans; Mice; Muscle, Skeletal; Vibration
PubMed: 35322859
DOI: 10.3892/mmr.2022.12698 -
Scientific Reports Jul 2021Mechanical stimulation has benefits for muscle mass and function. Passive stretching is widely performed in clinical rehabilitation medicine. However, the hypertrophic...
Mechanical stimulation has benefits for muscle mass and function. Passive stretching is widely performed in clinical rehabilitation medicine. However, the hypertrophic effects of passive repetitive stretching on senescent skeletal muscles against muscle atrophy remain unknown. We used senescence-accelerated model SAM-P8 mice. The gastrocnemius muscle was passively repetitive stretched by manual ankle dorsiflexion for 15 min, 5 days a week for 2 weeks under deep anesthesia. We examined the effects of passive stretching on muscle mass, myofiber cross-sectional area, muscle fiber type composition, satellite cell and myonuclei content, signaling pathways involved in muscle protein synthesis, and myogenic regulatory factors. The gastrocnemius muscle weight and fiber cross-sectional area of the stretched side was found greater compared with that of the unstretched side. Passive repetitive stretching increased the mRNA expression level of Akt, p70S6K, 4E-BP1, Myf5, myogenin, MuRF1.The phosphorylation level of p70S6K significantly increased in the stretched muscles, whereas of Akt and 4E-BP1 remained unchanged, compared to the unstretched side. The Pax7+ cells and myonuclei content did not differ between the stretched and unstretched muscles. These findings suggest that the hypertrophic or suppressed atrophic observation in the stretched muscles are mainly attributable to the protein turnover provoked by stretching. These findings are applicable to clinical muscle strengthening and sarcopenia prevention.
Topics: Adaptor Proteins, Signal Transducing; Animals; Cell Cycle Proteins; Mice; Muscle Fibers, Skeletal; Muscle Proteins; Muscle Stretching Exercises; Muscle, Skeletal; Myogenic Regulatory Factor 5; Organ Size; Proto-Oncogene Proteins c-akt; RNA, Messenger; Ribosomal Protein S6 Kinases, 70-kDa; Sarcopenia; Tripartite Motif Proteins; Ubiquitin-Protein Ligases
PubMed: 34315961
DOI: 10.1038/s41598-021-94709-0 -
International Journal of Molecular... Dec 2021A large set of FoxOs-dependent genes play a primary role in controlling muscle mass during hindlimb unloading. Mitochondrial dysfunction can modulate such a process. We...
A large set of FoxOs-dependent genes play a primary role in controlling muscle mass during hindlimb unloading. Mitochondrial dysfunction can modulate such a process. We hypothesized that endurance exercise before disuse can protect against disuse-induced muscle atrophy by enhancing peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) expression and preventing mitochondrial dysfunction and energy-sensing AMP-activated protein kinase (AMPK) activation. We studied cross sectional area (CSA) of muscle fibers of gastrocnemius muscle by histochemistry following 1, 3, 7, and 14 days of hindlimb unloading (HU). We used Western blotting and qRT-PCR to study mitochondrial dynamics and FoxOs-dependent atrogenes' expression at 1 and 3 days after HU. Preconditioned animals were submitted to moderate treadmill exercise for 7 days before disuse. Exercise preconditioning protected the gastrocnemius from disuse atrophy until 7 days of HU. It blunted alterations in mitochondrial dynamics up to 3 days after HU and the expression of most atrogenes at 1 day after disuse. In preconditioned , the activation of atrogenes resumed 3 days after HU when mitochondrial dynamics, assessed by profusion and pro-fission markers (mitofusin 1, MFN1, mitofusin 2, MFN2, optic atrophy 1, OPA1, dynamin related protein 1, DRP1 and fission 1, FIS1), PGC1α levels, and AMPK activation were at a basal level. Therefore, the normalization of mitochondrial dynamics and function was not sufficient to prevent atrogenes activation just a few days after HU. The time course of sirtuin 1 (SIRT1) expression and content paralleled the time course of atrogenes' expression. In conclusion, seven days of endurance exercise counteracted alterations of mitochondrial dynamics and the activation of atrogenes early into disuse. Despite the normalization of mitochondrial dynamics, the effect on atrogenes' suppression died away within 3 days of HU. Interestingly, muscle protection lasted until 7 days of HU. A longer or more intense exercise preconditioning may prolong atrogenes suppression and muscle protection.
Topics: Animals; Biomarkers; Hindlimb; Hindlimb Suspension; Male; Mice; Mice, Inbred C57BL; Mitochondrial Dynamics; Muscle, Skeletal; Muscular Atrophy; Muscular Disorders, Atrophic; Physical Conditioning, Animal
PubMed: 35008572
DOI: 10.3390/ijms23010148 -
Journal of Ultrasound Jun 2021The medial gastrocnemius is the most commonly injured muscle in the calf, and while traumatic lesions of the medial gastrocnemius are frequently described in the medical...
The medial gastrocnemius is the most commonly injured muscle in the calf, and while traumatic lesions of the medial gastrocnemius are frequently described in the medical literature and clinical and sonographic diagnoses are easy, those of the soleus are less easily recognisable clinically or by sonography. We present a case of traumatic lesions of the medial gastrocnemius, diagnosed clinically and with ultrasound, while MRI also detected two lesions of the soleus. The case presented and the review of the literature highlight how clinical and ultrasound examinations can lead to misunderstandings about traumatic injury to the soleus.
Topics: Humans; Magnetic Resonance Imaging; Muscle, Skeletal; Ultrasonography
PubMed: 33400251
DOI: 10.1007/s40477-020-00555-7 -
Experimental Physiology Aug 2021What is the central question of this study? What are the in vivo operating lengths of the gastrocnemius muscle in children who idiopathically toe-walk? What is the main...
NEW FINDINGS
What is the central question of this study? What are the in vivo operating lengths of the gastrocnemius muscle in children who idiopathically toe-walk? What is the main finding and its importance? Children who idiopathically toe-walk operate at more plantarflexed positions but at longer fascicle lengths than typically developing children during gait. However, these ranges utilised during gait correspond to where children who idiopathically toe-walk are optimally strong. This should be considered when prescribing clinical treatments to restore typical gait.
ABSTRACT
Children who idiopathically toe-walk (ITW) habitually operate at greater plantarflexion angles than typically developing (TD) children, which might result in shorter, sub-optimal gastrocnemius fascicle lengths. However, currently no experimental evidence exists to substantiate this notion. Five children who ITW and 14 TD children completed a gait analysis, whilst gastrocnemius fascicle behaviour was simultaneously quantified using ultrasound. The moment-angle (hip, knee and ankle) and moment-length (gastrocnemius) relationships were determined from isometric maximum voluntary contractions (MVC) on an isokinetic dynamometer combined with ultrasound. During gait, children who ITW operated at more plantarflexed angles (Δ = 20°; P = 0.013) and longer muscle fascicle lengths (Δ = 12 mm; P = 0.008) than TD children. During MVC, no differences in the peak moment of any joint were found. However, peak plantarflexor moment occurred at significantly more plantarflexed angles (-16 vs. 1°; P = 0.010) and at longer muscle fascicle lengths (44 vs. 37 mm; P = 0.001) in children who ITW than TD children. Observed alterations in the moment-angle and moment-length relationships of children who ITW coincided with the ranges used during gait. Therefore, the gastrocnemius muscle in children who ITW operates close to the peak of the force-length relationship, similarly to TD children. Thus, this study indicates that idiopathic toe-walking is truly an ankle joint pathology, and children who ITW present with substantial alterations in the gastrocnemius muscle functional properties, which appear well adapted to the characteristic demands of equinus gait. These findings should be considered when prescribing clinical treatments to restore typical gait.
Topics: Ankle Joint; Biomechanical Phenomena; Child; Gait; Humans; Muscle, Skeletal; Toes; Walking
PubMed: 34159660
DOI: 10.1113/EP089658 -
Skeletal Muscle Oct 2019Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is...
BACKGROUND
Skeletal muscle mass and strength are crucial determinants of health. Muscle mass loss is associated with weakness, fatigue, and insulin resistance. In fact, it is predicted that controlling muscle atrophy can reduce morbidity and mortality associated with diseases such as cancer cachexia and sarcopenia.
METHODS
We analyzed gene expression data from muscle of mice or human patients with diverse muscle pathologies and identified LMCD1 as a gene strongly associated with skeletal muscle function. We transiently expressed or silenced LMCD1 in mouse gastrocnemius muscle or in mouse primary muscle cells and determined muscle/cell size, targeted gene expression, kinase activity with kinase arrays, protein immunoblotting, and protein synthesis levels. To evaluate force, calcium handling, and fatigue, we transduced the flexor digitorum brevis muscle with a LMCD1-expressing adenovirus and measured specific force and sarcoplasmic reticulum Ca release in individual fibers. Finally, to explore the relationship between LMCD1 and calcineurin, we ectopically expressed Lmcd1 in the gastrocnemius muscle and treated those mice with cyclosporine A (calcineurin inhibitor). In addition, we used a luciferase reporter construct containing the myoregulin gene promoter to confirm the role of a LMCD1-calcineurin-myoregulin axis in skeletal muscle mass control and calcium handling.
RESULTS
Here, we identify LIM and cysteine-rich domains 1 (LMCD1) as a positive regulator of muscle mass, that increases muscle protein synthesis and fiber size. LMCD1 expression in vivo was sufficient to increase specific force with lower requirement for calcium handling and to reduce muscle fatigue. Conversely, silencing LMCD1 expression impairs calcium handling and force, and induces muscle fatigue without overt atrophy. The actions of LMCD1 were dependent on calcineurin, as its inhibition using cyclosporine A reverted the observed hypertrophic phenotype. Finally, we determined that LMCD1 represses the expression of myoregulin, a known negative regulator of muscle performance. Interestingly, we observed that skeletal muscle LMCD1 expression is reduced in patients with skeletal muscle disease.
CONCLUSIONS
Our gain- and loss-of-function studies show that LMCD1 controls protein synthesis, muscle fiber size, specific force, Ca handling, and fatigue resistance. This work uncovers a novel role for LMCD1 in the regulation of skeletal muscle mass and function with potential therapeutic implications.
Topics: Animals; Calcineurin; Calcineurin Inhibitors; Calcium; Cells, Cultured; Co-Repressor Proteins; Gene Expression Regulation; Humans; Hypertrophy; LIM Domain Proteins; Mice; Mice, Inbred C57BL; Mice, SCID; Mice, Transgenic; Muscle Fibers, Skeletal; Muscle Proteins; Muscle Strength; Muscle, Skeletal; Muscular Diseases; RNA, Messenger; Signal Transduction
PubMed: 31666122
DOI: 10.1186/s13395-019-0214-1 -
Experimental Gerontology Jan 2019Reloading of atrophied muscles after hindlimb suspension (HLS) can induce muscle injury and prolong recovery after disuse in old rats, especially in fast contracting...
Reloading of atrophied muscles after hindlimb suspension (HLS) can induce muscle injury and prolong recovery after disuse in old rats, especially in fast contracting muscles. Less is known about the responses in mice and whether fast and slow muscles from geriatric mice will respond in a similar fashion to HLS unloading and recovery (HLS + R). Furthermore, while slow muscles undergo atrophy with disuse, they typically are more resistant to sarcopenia than fast contracting muscles. Geriatric (28 mo. of age) male C57BL/6 mice were randomly placed into 3 groups. These included HLS for 14 days n = 9, and HLS followed by 14 days of reloading recovery (HLS + R; n = 9), or normal ambulatory cage controls (n = 9). Control mice were not exposed to unloading. Electrically evoked maximal muscle function was assessed in vivo in anesthetized mice at baseline, after 14 days of HLS or HLS + R. As expected, HLS significantly reduced body weight, wet weight of gastrocnemius and soleus muscles and in vivo maximal force. There were no differences in vivo fatigability of the plantar flexor muscles and overall fiber size. There were only minor fiber type distribution and frequency distribution of fiber sizes that differ between HLS + R and control gastrocnemius and soleus muscles. Soleus muscle wet weight had recovered to control levels after reloading, but type I/IIA fibers in the soleus muscles were significantly smaller after HLS + R than control muscles. In contrast, gastrocnemius muscle wet weight did not recover to control levels after reloading. Plantar flexion muscle force (primarily influenced by the gastrocnemius muscles) did not recover in HLS + R conditions as compared to HLS conditions and both were lower than control force production signaling for apoptosis, autophagy and anabolic markers were not different between control and HLS + R gastrocnemius and soleus muscles in geriatric mice. These results suggest that molecular signaling does not explain attenuated ability to regain muscle wet weight, fiber size or muscle force production after HLS in geriatric mice. It is possible that fluid shifts, reduced blood flow, or shortened muscle fibers which failed to regain control lengths contributed to the attenuation of muscle wet weight after HLS and reloading and this affected force production. Further work is needed to determine if altered/loss of neural activity contributed to the inability of geriatric mice to regain gastrocnemius muscle weight and function after HLS and reloading.
Topics: Aging; Animals; Hindlimb Suspension; Isometric Contraction; Male; Mice; Mice, Inbred C57BL; Muscle Fibers, Skeletal; Muscle, Skeletal; Muscular Atrophy; Organ Size
PubMed: 30448397
DOI: 10.1016/j.exger.2018.11.011 -
Journal of Musculoskeletal & Neuronal... Sep 2021To examine whether genetic variability plays a role in skeletal muscle response to disuse.
OBJECTIVE
To examine whether genetic variability plays a role in skeletal muscle response to disuse.
METHODS
We examined skeletal muscle response to disuse in five different strains of mice: CAST/EiJ, NOD/ShiLtJ, NZO/HILtJ, 129S1/SvImJ and A/J. Mice had one limb immobilized by a cast for three weeks.
RESULTS
Response to immobilization was dependent on the strain of mice. Skeletal muscle mass/body weight was decreased by immobilization in all strains except 1291/SvImJ. Immobilization decreased absolute skeletal muscle mass in quadriceps and gastrocnemius in NOD/ShiltJ and NZO/HILtJ mice. Three weeks of immobilization resulted in an increase in quadriceps levels of atrogenes in CAST/EiJ. Immobilization resulted in an increase in quadriceps and gastrocnemius levels of in CAST/EiJ. A similar trend was observed for in gastrocnemius muscle. Immobilization resulted in a decrease of the p-p70S6K1/total p706SK1 ratio in quadriceps of NOD/ShiLtJ mice and the gastrocnemius of A/J mice. Immobilization did not affect the p-4EBP1/total 4EBP1 ratio in quadriceps of any of the strains examined. However, the p-4EBP1/total 4EBP1 ratio in gastrocnemius was greater in immobilized, relative to control, limbs in CAST/EiJ mice.
CONCLUSION
Genetic variability affects the response of skeletal muscle to disuse.
Topics: Animals; Immobilization; Mice; Mice, Inbred NOD; Muscle, Skeletal; Muscular Atrophy; Quadriceps Muscle
PubMed: 34465678
DOI: No ID Found -
Cell Stress & Chaperones Mar 2021The present study aimed to investigate the differential response of oxidative (soleus) and glycolytic (gastrocnemius) muscles to heat-induced endoplasmic reticulum (ER)...
The present study aimed to investigate the differential response of oxidative (soleus) and glycolytic (gastrocnemius) muscles to heat-induced endoplasmic reticulum (ER) stress. It was hypothesized that due to compositional and functional differences, both muscles respond differently to acute heat stress. To address this, male Sprague Dawley rats (12/group) were subjected to thermoneutral (25 °C) or heat stress (42 °C) conditions for 1 h. Soleus and gastrocnemius muscles were removed for analysis post-exposure. A significant increase in body temperature and free radical generation was observed in both the muscles following heat exposure. This further caused a significant increase in protein carbonyl content, AOPP, and lipid peroxidation in heat-stressed muscles. These changes were more pronounced in heat-stressed soleus compared to the gastrocnemius muscle. Accumulation of unfolded, denatured proteins results in ER stress, causing activation of unfolded protein response (UPR) pathway. The expressions of UPR transducers were significantly higher in soleus as compared to the gastrocnemius muscle. A significant elevation in resting intracellular calcium ion was also observed in heat-stressed soleus muscle. Overloading of cells with misfolded proteins in soleus muscle activated ER-induced apoptosis as indicated by significant upregulation of C/EBP homologous protein and Caspase12. The study provides a detailed mechanistic representation of the differential response of muscles toward UPR under heat stress. Data suggests that soleus majorly being an oxidative muscle is more prone to heat stress-induced insult indicated by enhanced apoptosis. This study may aid in devising mitigation strategies to improve muscle performance under heat stress.
Topics: Animals; Apoptosis; Endoplasmic Reticulum Stress; Heat-Shock Response; Male; Muscle, Skeletal; Oxidative Stress; Rats; Rats, Sprague-Dawley; Unfolded Protein Response
PubMed: 33210173
DOI: 10.1007/s12192-020-01178-x -
Muscle & Nerve Dec 2019Physical inactivity significantly contributes to loss of muscle mass and performance in bed-bound patients. Loss of skeletal muscle mitochondrial content has been...
INTRODUCTION
Physical inactivity significantly contributes to loss of muscle mass and performance in bed-bound patients. Loss of skeletal muscle mitochondrial content has been well-established in muscle unloading models, but the underlying molecular mechanism remains unclear. We hypothesized that apparent unloading-induced loss of muscle mitochondrial content is preceded by increased mitophagy- and decreased mitochondrial biogenesis-signaling during the early stages of unloading.
METHODS
We analyzed a comprehensive set of molecular markers involved in mitochondrial-autophagy, -biogenesis, -dynamics, and -content, in the gastrocnemius muscle of C57BL/6J mice subjected to 0- and 3-days hind limb suspension, and in biopsies from human vastus lateralis muscle obtained before and after 7 days of one-leg immobilization.
RESULTS
In both mice and men, short-term skeletal muscle unloading results in molecular marker patterns indicative of increased receptor-mediated mitophagy and decreased mitochondrial biogenesis regulation, before apparent loss of mitochondrial content.
DISCUSSION
These results emphasize the early-onset of skeletal muscle disuse-induced mitochondrial remodeling.
Topics: Adolescent; Adult; Animals; Casts, Surgical; Gene Expression; Hindlimb Suspension; Humans; Immobilization; Male; Mice; Mice, Inbred C57BL; Mitochondria, Muscle; Mitophagy; Muscle, Skeletal; Organelle Biogenesis; Quadriceps Muscle; Weight-Bearing; Young Adult
PubMed: 31495926
DOI: 10.1002/mus.26702