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Keywords = fast-twitch muscles

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31 pages, 4843 KiB  
Review
Glucocorticoid-Mediated Skeletal Muscle Atrophy: Molecular Mechanisms and Potential Therapeutic Targets
by Uttapol Permpoon, Jiyeong Moon, Chul Young Kim and Tae-gyu Nam
Int. J. Mol. Sci. 2025, 26(15), 7616; https://doi.org/10.3390/ijms26157616 - 6 Aug 2025
Abstract
Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose [...] Read more.
Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article
(This article belongs to the Special Issue Understanding Aging in Health and Disease)
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26 pages, 5469 KiB  
Review
Neuromuscular Activity Determines, at Least in Part, the Motoneuron, Nerve and Muscle Properties Under Normal Conditions and After Nerve Injury
by Tessa Gordon
Int. J. Mol. Sci. 2025, 26(14), 6891; https://doi.org/10.3390/ijms26146891 - 17 Jul 2025
Viewed by 295
Abstract
Whether pattern or amount of daily activity determines neuromuscular properties is the focus of this review. The fast-to-slow conversion of many properties of fast-twitch muscles, by stimulating their nerves electrically with the continuous low-frequency pattern typical of slow motoneurons, argued that muscle properties [...] Read more.
Whether pattern or amount of daily activity determines neuromuscular properties is the focus of this review. The fast-to-slow conversion of many properties of fast-twitch muscles, by stimulating their nerves electrically with the continuous low-frequency pattern typical of slow motoneurons, argued that muscle properties are determined by their pattern of activity. However, the composition of the motor units (MUs) in almost all muscles is heterogeneous, with the MUs grouped into slow, fast-fatigue-resistant and fast-fatigable types that match corresponding histochemical fiber types. Nonetheless, their contractile forces lie on a continuum, with MUs recruited into activity in order of their size. This ‘size principle’ of MU organization and function applies in normally innervated and reinnervated muscles and, importantly, begs the question of whether it is the amount rather than the pattern of the MU activation that determines their properties. Experimental evidence that uniform daily amounts of ~<0.5, 5%, and 50% ES, converted motoneuron, nerve, and muscle properties to one physiological and histochemical type, argued in favor of the amount of activity determining MU properties. Yet, that the properties were not confined to the expected narrow range argued that factors other than the pattern and/or amount of neuromuscular activity must be considered. These include the progressive increase in the synaptic inputs onto motoneurons. The range of the effects of endurance and intermittent exercise programs on healthy subjects and those suffering nerve injuries and disease is also consistent with the argument that factors other than pattern or amount of neuromuscular activity should be investigated. Full article
(This article belongs to the Section Molecular Neurobiology)
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17 pages, 1855 KiB  
Article
Effects of Muscle Fiber Composition on Meat Quality, Flavor Characteristics, and Nutritional Traits in Lamb
by Yu Fu, Yang Chen, Xuewen Han, Dandan Tan, Jinlin Chen, Cuiyu Lai, Xiaofan Yang, Xuesong Shan, Luiz H. P. Silva and Huaizhi Jiang
Foods 2025, 14(13), 2309; https://doi.org/10.3390/foods14132309 - 29 Jun 2025
Cited by 1 | Viewed by 477
Abstract
Skeletal muscle fiber type composition critically influences lamb meat quality. This study examined the relationships between muscle fiber types and key quality traits, including tenderness, color, lipid and amino acid profiles, and volatile flavor compounds. MyHC I (slow-twitch oxidative fibers) positively correlated with [...] Read more.
Skeletal muscle fiber type composition critically influences lamb meat quality. This study examined the relationships between muscle fiber types and key quality traits, including tenderness, color, lipid and amino acid profiles, and volatile flavor compounds. MyHC I (slow-twitch oxidative fibers) positively correlated with desirable traits such as increased redness, water-holding capacity, unsaturated fatty acids, and essential amino acids. Conversely, MyHC IIb (fast glycolytic fibers) was linked to reduced tenderness and higher levels of off-flavor compounds. MyHC IIa and IIx showed minimal effects. Untargeted metabolomics comparing muscles with high versus low slow-twitch fiber proportions revealed differential metabolites enriched in sphingolipid and arginine-proline metabolism pathways. These results suggest that a higher proportion of oxidative fibers enhances both the sensory and nutritional qualities of lamb meat by modulating lipid metabolism, amino acid availability, and flavor formation. Full article
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18 pages, 7866 KiB  
Article
Apocynin Mitigates Diabetic Muscle Atrophy by Lowering Muscle Triglycerides and Oxidative Stress
by Sarai Sánchez-Duarte, Elizabeth Sánchez-Duarte, Luis A. Sánchez-Briones, Esperanza Meléndez-Herrera, Ma. Antonia Herrera-Vargas, Sergio Márquez-Gamiño, Karla S. Vera-Delgado and Rocío Montoya-Pérez
Int. J. Mol. Sci. 2025, 26(12), 5636; https://doi.org/10.3390/ijms26125636 - 12 Jun 2025
Viewed by 588
Abstract
Diabetic muscular atrophy is a complication of diabetes mellitus that can decrease quality of life. Its complex mechanisms include alterations in proteolytic pathways, oxidative stress, and intracellular lipid accumulation. NADPH oxidase enzymes (NOX) play a key role in the production of ROS, contributing [...] Read more.
Diabetic muscular atrophy is a complication of diabetes mellitus that can decrease quality of life. Its complex mechanisms include alterations in proteolytic pathways, oxidative stress, and intracellular lipid accumulation. NADPH oxidase enzymes (NOX) play a key role in the production of ROS, contributing to oxidative damage and insulin resistance. Apocynin, a NOX inhibitor, has antioxidant and anti-inflammatory effects, suggesting its therapeutic potential in various diabetic complications. This study evaluated the impact of apocynin on the mechanisms of muscle atrophy in slow- and fast-twitch muscles of diabetic rats. Diabetes was induced in male Wistar rats by intraperitoneal injection of a single dose of streptozotocin (60 mg/kg). Apocynin treatment (3 mg/kg/day) was administered for 8 weeks. Fasting blood glucose levels, lipid profile, and weight gain were measured. Both slow-twitch (soleus) and fast-twitch (extensor digitorum longus, EDL) skeletal muscles were weighed and used to assess triglycerides (TG) content, histological analysis, lipid peroxidation levels, and gene expression evaluated by qRT-PCR. Apocynin reduced blood glucose levels, improved body weight, and exhibited hypolipidemic effects. It significantly increased muscle weight in EDL and soleus, especially in EDL muscle, lowering triglycerides, lipid peroxidation, and increasing fiber size. Additionally, it decreased mRNA expression levels of MuRF-1, atrogin-1, myostatin and p47phox mRNA and upregulated PGC-1α and follistatin mRNA. Apocynin exerted a myoprotective effect by mitigating muscle atrophy in diabetic rats. Its effects were differentially mediated on TG accumulation and muscle fiber size, reducing oxidative stress, atrogene expression, and positively regulating PGC-1α. Full article
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19 pages, 306 KiB  
Review
The Role of High-Intensity Interval Training (HIIT) in Neuromuscular Adaptations: Implications for Strength and Power Development—A Review
by Chi-Hsiang Hung, Chun-Hsien Su and Dong Wang
Life 2025, 15(4), 657; https://doi.org/10.3390/life15040657 - 16 Apr 2025
Cited by 1 | Viewed by 6863
Abstract
High-intensity Interval Training (HIIT) is increasingly recognized for enhancing neuromuscular function, strength, power, and overall athletic performance. This review systematically examined peer-reviewed studies published between 2000 and 2025, focusing on HIIT’s impact on motor unit recruitment, muscle fiber composition, neuromuscular efficiency, maximal strength, [...] Read more.
High-intensity Interval Training (HIIT) is increasingly recognized for enhancing neuromuscular function, strength, power, and overall athletic performance. This review systematically examined peer-reviewed studies published between 2000 and 2025, focusing on HIIT’s impact on motor unit recruitment, muscle fiber composition, neuromuscular efficiency, maximal strength, rate of force development (RFD), muscle hypertrophy, and power output. Findings indicate that HIIT significantly improves neuromuscular activation by increasing motor unit recruitment and synchronization, particularly in fast-twitch fibers essential for explosive movements. HIIT also promotes shifts toward Type II and hybrid Type IIa fibers, enhancing strength and endurance. However, despite its effectiveness in boosting RFD and explosive power, HIIT is less efficient than traditional resistance training for maximizing absolute strength and hypertrophy due to insufficient progressive overload. Integrating resistance-based and plyometric-based HIIT protocols emerged as an effective strategy to enhance strength and power concurrently. Effective periodization and recovery strategies, including active recovery and targeted nutrition, help mitigate fatigue and optimize adaptations. Notable research gaps include the long-term impacts of HIIT on neuromuscular function and the efficacy of individualized HIIT protocols based on specific athlete characteristics. Future research should focus on refining HIIT protocols for different sports, exploring its synergy with traditional resistance training, and assessing long-term adaptations to sustain strength and power gains. HIIT presents a valuable, time-efficient complement to conventional training methods for improving strength, power, and neuromuscular efficiency. Full article
(This article belongs to the Special Issue Effects of Exercise Training on Muscle Function)
20 pages, 6552 KiB  
Article
Pilot Study on the Profiling and Functional Analysis of mRNA, miRNA, and lncRNA in the Skeletal Muscle of Mongolian Horses, Xilingol Horses, and Grassland-Thoroughbreds
by Wenqi Ding, Wendian Gong, Tugeqin Bou, Lin Shi, Yanan Lin, Huize Wu, Manglai Dugarjaviin and Dongyi Bai
Animals 2025, 15(8), 1123; https://doi.org/10.3390/ani15081123 - 13 Apr 2025
Cited by 1 | Viewed by 557
Abstract
Muscle fibers, as the fundamental units of muscle tissue, play a crucial role in determining skeletal muscle function through their growth, development, and composition. To investigate changes in muscle fiber types and their regulatory mechanisms in Mongolian horses (MG), Xilingol horses (XL), and [...] Read more.
Muscle fibers, as the fundamental units of muscle tissue, play a crucial role in determining skeletal muscle function through their growth, development, and composition. To investigate changes in muscle fiber types and their regulatory mechanisms in Mongolian horses (MG), Xilingol horses (XL), and Grassland-Thoroughbreds (CY), we conducted histological and bioinformatic analyses on the gluteus medius muscle of these three horse breeds. Immunofluorescence analysis revealed that Grassland-Thoroughbreds had the highest proportion of fast-twitch muscle fibers at 78.63%, while Mongolian horses had the lowest proportion at 57.54%. Whole-transcriptome analysis identified 105 differentially expressed genes (DEGs) in the CY vs. MG comparison and 104 DEGs in the CY vs. XL comparison. Time-series expression profiling grouped the DEGs into eight gene sets, with three sets showing significantly up-regulated or down-regulated expression patterns (p < 0.05). Additionally, 280 differentially expressed long non-coding RNAs (DELs) were identified in CY vs. MG, and 213 DELs were identified in CY vs. XL. A total of 32 differentially expressed microRNAs (DEMIRs) were identified in CY vs. MG, while 44 DEMIRs were found in CY vs. XL. Functional enrichment analysis indicated that the DEGs were significantly enriched in essential biological processes, such as actin filament organization, muscle contraction, and protein phosphorylation. KEGG pathway analysis showed their involvement in key signaling pathways, including the mTOR signaling pathway, FoxO signaling pathway, and HIF-1 signaling pathway. Furthermore, functional variation-based analyses revealed associations between non-coding RNAs and mRNAs, with some non-coding RNAs targeting genes potentially related to muscle function regulation. These findings provide valuable insights into the molecular basis for the environmental adaptability, athletic performance, and muscle characteristics in horses, offering new perspectives for the breeding of Grassland-Thoroughbreds. Full article
(This article belongs to the Special Issue Equine Genetics, Evolution, and Breeds)
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17 pages, 4801 KiB  
Article
Dual Action of Pueraria montana var. lobata Extract on Myogenesis and Muscle Atrophy
by So Young Eun, Chang Hoon Lee, Yoon-Hee Cheon, Chong Hyuk Chung, Myeung Su Lee and Ju-Young Kim
Nutrients 2025, 17(7), 1217; https://doi.org/10.3390/nu17071217 - 30 Mar 2025
Viewed by 799
Abstract
Background/Objectives: Muscle atrophy, defined by diminished muscle mass and function, is a notable concern associated with aging, disease, and glucocorticoid treatment. Pueraria montana var. lobata extract (PMLE) demonstrates multiple bioactive properties, such as antioxidant, anti-inflammatory, and metabolic regulatory activities; however, its role [...] Read more.
Background/Objectives: Muscle atrophy, defined by diminished muscle mass and function, is a notable concern associated with aging, disease, and glucocorticoid treatment. Pueraria montana var. lobata extract (PMLE) demonstrates multiple bioactive properties, such as antioxidant, anti-inflammatory, and metabolic regulatory activities; however, its role in muscle atrophy has not been extensively investigated to date. This study examined how PMLE influences both muscle cell differentiation and dexamethasone (DEX)-induced muscle degeneration by focusing on the underlying molecular mechanisms. Methods: This study examined the effects of PMLE on myogenic differentiation and DEX-induced muscle atrophy. C2C12 myoblasts were treated with PMLE (10–100 ng/mL) and assessed for changes in the expression of myogenesis-related genes and activation of Akt/mTOR and AMPK/SIRT1/PGC-1α signaling cascades. In vivo, a DEX-induced muscle atrophy model was used to assess muscle mass, fiber morphology, and molecular changes. Results: PMLE PMLE promoted muscle cell development by increasing the expression of MyHC, MyoD, and myogenin while activating protein synthesis and mitochondrial biogenesis pathways. PMLE counteracted DEX-induced myotube atrophy, restoring myotube diameter and promoting cellular fusion in vitro. In vivo, PMLE mitigated muscle degradation in fast-twitch muscle groups and reversed DEX-induced suppression of key anabolic and mitochondrial pathways. Conclusions: These findings suggest that PMLE promotes myogenic differentiation and protects against muscle atrophy by regulating critical molecular pathways, indicating its promise as a treatment candidate for conditions involving muscle wasting. Further studies are required to assess its clinical application and long-term safety efficacy. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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15 pages, 717 KiB  
Article
A Study on 10-Week Combined Aerobic and Resistance Training Exercise Prescription for Female Patients with Pelvic Floor Dysfunction
by Lu Zhang, Jingbo He, Quancheng Zhang and Ling Wang
Healthcare 2025, 13(6), 592; https://doi.org/10.3390/healthcare13060592 - 8 Mar 2025
Viewed by 2706
Abstract
Background/Objectives: Female pelvic floor dysfunction (FPFD) is a prevalent condition affecting postpartum women. This study aims to evaluate the effectiveness of a 10-week combined aerobic and resistance training exercise prescription in improving pelvic floor muscle strength and function in postpartum women with [...] Read more.
Background/Objectives: Female pelvic floor dysfunction (FPFD) is a prevalent condition affecting postpartum women. This study aims to evaluate the effectiveness of a 10-week combined aerobic and resistance training exercise prescription in improving pelvic floor muscle strength and function in postpartum women with FPFD. Methods: Thirty postpartum women diagnosed with FPFD underwent a 10-week exercise intervention. This study adopted a single-group pre–post design. Pelvic floor muscle electromyography assessment indicators were measured before and after the intervention. Results: The exercise intervention significantly improved the maximum value of fast-twitch muscle fibers (type II) and the average value of slow-twitch muscle fibers (type I) while reducing resting tension and variability. Conclusions: A 10-week combined aerobic and resistance training exercise prescription effectively improves pelvic floor muscle strength in postpartum women. It enhances the maximum value of fast-twitch (type II) muscle fibers, reduces rise and recovery times, and improves slow-twitch (type I) muscle fiber function, including increasing the mean value and reducing variability, rise time, and recovery time. Full article
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14 pages, 867 KiB  
Article
The Impact of Fucoidan Extracts on Heat-Stress-Induced Loss of In Vitro Fast-Twitch Muscle Function in Mice
by Samantha T. C. Kucewicz, Stefan Piantella, Jarrod E. Church, Caroline J. Taylor and Chris van der Poel
Muscles 2025, 4(1), 6; https://doi.org/10.3390/muscles4010006 - 27 Feb 2025
Viewed by 998
Abstract
Elevated temperatures have been shown to decrease muscle force production, with potential causes including protein unfolding, enzyme denaturation, and reactive oxygen species (ROS). This study aimed to investigate whether fucoidan, a compound derived from brown seaweed, could mitigate heat-stress-induced loss of muscle function. [...] Read more.
Elevated temperatures have been shown to decrease muscle force production, with potential causes including protein unfolding, enzyme denaturation, and reactive oxygen species (ROS). This study aimed to investigate whether fucoidan, a compound derived from brown seaweed, could mitigate heat-stress-induced loss of muscle function. C57BL/6 mice were orally administered fucoidan (400 mg/kg/day) from one of two different seaweed species Fucus vesiculosus (FVF) or Undaria pinnatifida (UPF) or vehicle control for seven consecutive days. Subsequently, the in vitro muscle function of the fast-twitch extensor digitorum longus (EDL) was assessed at either 25 °C (control) or 43 °C (heat stress). Functional analysis was complemented with gene analysis and the C2C12 myoblast heat-stress assay. The temperature (43 °C)-induced loss of force produced by the EDL muscle was significantly attenuated by fucoidan from FVF but not UPF. Fucoidan from UPF did not affect gene expression levels, whereas fucoidan from FVF significantly increased the expression levels of HSP90. In mouse C2C12 myoblasts, heat stress induced a significant increase in ROS production which was significantly reduced by both fucoidan species. These results suggest fucoidan extracted from Fucus vesiculosus may be an effective preventive strategy to protect against heat-induced loss of muscle strength in fast-twitch muscles. Full article
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22 pages, 8089 KiB  
Article
Effects of 3-(4-Hydroxy-3-methoxyphenyl)propionic Acid on Regulating Oxidative Stress and Muscle Fiber Composition
by Yishan Tong, Sihui Ma, Riyo Awa, Takashi Tagawa, Yasuhiro Seki, Tiehan Cao, Haruki Kobori and Katsuhiko Suzuki
Nutrients 2025, 17(4), 668; https://doi.org/10.3390/nu17040668 - 13 Feb 2025
Viewed by 1427
Abstract
Background/Objectives: Our previous study demonstrated that 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) administration improved grip strength and reduced blood urea nitrogen levels, but its underlying mechanisms remain unclear. This study aimed to investigate the effects of HMPA on oxidative stress and muscle fiber composition, emphasizing [...] Read more.
Background/Objectives: Our previous study demonstrated that 3-(4-hydroxy-3-methoxyphenyl)propionic acid (HMPA) administration improved grip strength and reduced blood urea nitrogen levels, but its underlying mechanisms remain unclear. This study aimed to investigate the effects of HMPA on oxidative stress and muscle fiber composition, emphasizing its potential role in modulating redox signaling pathways and influencing muscle development. Methods: Eight-week-old male C57BL/6 mice were orally administered HMPA solution (50 or 500 mg/kg/day) or distilled water (10 mL/kg) for 14 days, and then divided into sedentary and exhaustive exercise groups to evaluate oxidative stress status, myosin heavy chain (MHC) isoform expression, and underlying mechanisms. Results: Both low and high doses of HMPA reduced oxidative stress by decreasing plasma reactive oxygen metabolites. High-dose HMPA reduced plasma nitrite/nitrate levels and enhanced antioxidant capacity post-exercise, accompanied by changes in the mRNA abundance of antioxidant enzymes (e.g., Sod1 and Nqo1) and reductions in the mRNA abundance of nitric oxide synthases (e.g., Nos2 and Nos3) in the soleus. Additionally, high-dose HMPA administration increased the protein expression of MYH4 in the soleus, while low-dose HMPA enhanced the gene expression of Myh4 and Igf1, suggesting that HMPA may promote fast-twitch fiber hypertrophy through the activation of the IGF-1 pathway. Furthermore, low-dose HMPA significantly increased the gene expression of Sirt1 and Nrf1, as well as AMPK phosphorylation post-exercise, suggesting low-dose HMPA may improve mitochondrial biogenesis and exercise adaptation. Conclusions: These findings suggest that HMPA may serve as a dietary supplement to regulate redox balance, enhance antioxidant defenses, and promote the formation of fast-twitch fibers. Full article
(This article belongs to the Special Issue Nutritional Value and Health Benefits of Dietary Bioactive Compounds)
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15 pages, 3461 KiB  
Article
The Effect of Electrical Stimulation Strength Training on Lower Limb Muscle Activation Characteristics During the Jump Smash Performance in Badminton Based on the EMS and EMG Sensors
by Xinyu Lin, Yimin Hu and Yi Sheng
Sensors 2025, 25(2), 577; https://doi.org/10.3390/s25020577 - 20 Jan 2025
Cited by 3 | Viewed by 3954
Abstract
This study investigates the effects of electrical stimulation (EMS) combined with strength training on lower limb muscle activation and badminton jump performance, specifically during the “jump smash” movement. A total of 25 male badminton players, with a minimum of three years of professional [...] Read more.
This study investigates the effects of electrical stimulation (EMS) combined with strength training on lower limb muscle activation and badminton jump performance, specifically during the “jump smash” movement. A total of 25 male badminton players, with a minimum of three years of professional training experience and no history of lower limb injuries, participated in the study. Participants underwent three distinct conditions: baseline testing, strength training, and EMS combined with strength training. Each participant performed specific jump tests, including the jump smash and static squat jump, under each condition. Muscle activation was measured using electromyography (EMG) sensors to assess changes in the activation of key lower limb muscles. The EMS intervention involved targeted electrical pulses designed to stimulate both superficial and deep muscle fibers, aiming to enhance explosive strength and coordination in the lower limbs. The results revealed that the EMS + strength condition significantly improved performance in both the jump smash and static squat jump, as compared to the baseline and strength-only conditions (F = 3.39, p = 0.042; F = 3.67, p = 0.033, respectively). Additionally, increased activation of the rectus femoris (RF) was observed in the EMS + strength condition, indicating improved muscle recruitment and synchronization, likely due to the activation of fast-twitch fibers. No significant differences were found in the eccentric-concentric squat jump (F = 0.59, p = 0.561). The findings suggest that EMS, when combined with strength training, is an effective method for enhancing lower limb explosiveness and muscle activation in badminton players, offering a promising training approach for improving performance in high-intensity, explosive movements. Full article
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19 pages, 14588 KiB  
Article
Integrated Proteomic and Metabolomic Analysis of Muscle Atrophy Induced by Hindlimb Unloading
by Yuan Wang, Xi Li, Na Li, Jiawei Du, Xiaodong Qin, Xiqing Sun, Yongchun Wang and Chengfei Li
Biomolecules 2025, 15(1), 14; https://doi.org/10.3390/biom15010014 - 26 Dec 2024
Cited by 2 | Viewed by 1412
Abstract
Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue that lacks effective treatment. Hindlimb unloading is a commonly used model of muscle atrophy. However, the underlying mechanism of muscle [...] Read more.
Skeletal muscle atrophy, which is induced by factors such as disuse, spaceflight, certain medications, neurological disorders, and malnutrition, is a global health issue that lacks effective treatment. Hindlimb unloading is a commonly used model of muscle atrophy. However, the underlying mechanism of muscle atrophy induced by hindlimb unloading remains unclear, particularly from the perspective of the myocyte proteome and metabolism. We first used mass spectrometry for proteomic sequencing and untargeted metabolomics to analyze soleus muscle changes in rats with hindlimb unloading. The study found 1052 proteins and 377 metabolites (with the MS2 name) that were differentially expressed between the hindlimb unloading group and the control group. Proteins like ACTN3, MYH4, MYBPC2, and MYOZ1, typically found in fast-twitch muscles, were upregulated, along with metabolism-related proteins GLUL, GSTM4, and NDUFS4. Metabolites arachidylcarnitine and 7,8-dihydrobiopterin, as well as pathways like histidine, taurine, and hypotaurine metabolism, were linked to muscle atrophy. Protein and metabolism joint analyses revealed that some pathways, such as glutathione metabolism, ferroptosis, and lysosome pathways, were likely to be involved in soleus atrophy. In this study, we have applied integrated deep proteomic and metabolomic analyses. The upregulation of proteins that are expressed in fast-twitch fibers indicates the conversion of slow-twitch fibers to fast-twitch fibers under hindlimb unloading. In addition, some differentially abundant metabolites and pathways revealed the important role of metabolism in muscle atrophy of the soleus. As shown in the graphical abstract, our study provides insights into the pathogenesis and treatment of muscle atrophy that results from unloading by integrating proteomics and metabolomics of the soleus muscles. Full article
(This article belongs to the Section Bioinformatics and Systems Biology)
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15 pages, 4771 KiB  
Article
Long-Term Yo-Yo Dieting Exaggerates Liver Steatosis and Lesions but Preserves Muscle Performance in Male Zebrafish
by Tzu-Chieh Hsu, Chun-Hsien Chiang, I-Hsuan Liu, Chih-Yun Wang and Ching-Yi Chen
Int. J. Mol. Sci. 2024, 25(23), 13225; https://doi.org/10.3390/ijms252313225 - 9 Dec 2024
Cited by 1 | Viewed by 1265
Abstract
Weight regain within one year after weight loss is frequently observed and is referred to as yo-yo dieting or weight cycling. In this study, we explore the effects of yo-yo dieting on the liver, adipose tissue, and muscle characteristics of male zebrafish. Four-month-old [...] Read more.
Weight regain within one year after weight loss is frequently observed and is referred to as yo-yo dieting or weight cycling. In this study, we explore the effects of yo-yo dieting on the liver, adipose tissue, and muscle characteristics of male zebrafish. Four-month-old AB wild-type male zebrafish were randomly assigned to three groups: high-calorie intake (H, seven meals per day), low-calorie intake (L, two meals per day), and yo-yo diet (the low- and high-calorie alternation switched every two weeks) groups. Feeding the fish the H diet for over 8 weeks led to steatosis and damage to the liver. The yo-yo diet reduced liver lipid accumulation at week eight but caused a similar degree of lipid accumulation as the H diet thereafter. It was found that twenty weeks of yo-yo dieting actually exacerbated hepatic damage. Compared to the L diet, feeding the fish on the yo-yo and H diets for a period of 20 weeks significantly increased the size of muscle fibers, resulting in higher speed during burst swimming and a significant increase in the size and number of adipocytes in the abdominal tissue. To summarize, short-term yo-yo dieting was found to attenuate hepatosteatosis and maintain fast-twitch muscle function. Long-term yo-yo dieting preserved fast-twitch muscle function and muscle fiber size; however, it exacerbated the pathological changes in the liver. Full article
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13 pages, 1416 KiB  
Article
The ARK2N (C18ORF25) Genetic Variant Is Associated with Muscle Fiber Size and Strength Athlete Status
by Rukiye Çığırtaş, Celal Bulgay, Hasan Hüseyin Kazan, Onur Akman, Goran Sporiš, George John, Rinat A. Yusupov, Rinat I. Sultanov, Andrey V. Zhelankin, Ekaterina A. Semenova, Andrey K. Larin, Nikolay A. Kulemin, Edward V. Generozov, Damir Jurko and Ildus I. Ahmetov
Metabolites 2024, 14(12), 684; https://doi.org/10.3390/metabo14120684 - 5 Dec 2024
Cited by 2 | Viewed by 2007
Abstract
Background: Data on the genetic factors contributing to inter-individual variability in muscle fiber size are limited. Recent research has demonstrated that mice lacking the Arkadia (RNF111) N-terminal-like PKA signaling regulator 2N (Ark2n; also known as C18orf25) gene exhibit reduced muscle [...] Read more.
Background: Data on the genetic factors contributing to inter-individual variability in muscle fiber size are limited. Recent research has demonstrated that mice lacking the Arkadia (RNF111) N-terminal-like PKA signaling regulator 2N (Ark2n; also known as C18orf25) gene exhibit reduced muscle fiber size, contraction force, and exercise capacity, along with defects in calcium handling within fast-twitch muscle fibers. However, the role of the ARK2N gene in human muscle physiology, and particularly in athletic populations, remains poorly understood. The aim of this study was threefold: (a) to compare ARK2N gene expression between power and endurance athletes; (b) to analyze the relationship between ARK2N gene expression and muscle fiber composition; and (c) to investigate the association between the functional variant of the ARK2N gene, muscle fiber size, and sport-related phenotypes. Results: We found that ARK2N gene expression was significantly higher in power athletes compared to endurance athletes (p = 0.042) and was positively associated with the proportion of oxidative fast-twitch (type IIA) muscle fibers in untrained subjects (p = 0.017, adjusted for age and sex). Additionally, we observed that the ARK2N rs6507691 T allele, which predicts high ARK2N gene expression (p = 3.8 × 10−12), was associated with a greater cross-sectional area of fast-twitch muscle fibers in strength athletes (p = 0.015) and was over-represented in world-class strength athletes (38.6%; OR = 2.2, p = 0.023) and wrestlers (33.8%; OR = 1.8, p = 0.044) compared to controls (22.0%). Conclusions: In conclusion, ARK2N appears to be a gene specific to oxidative fast-twitch myofibers, with its functional variant being associated with muscle fiber size and strength-athlete status. Full article
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44 pages, 20348 KiB  
Article
Testing Green Tea Extract and Ammonium Salts as Stimulants of Physical Performance in a Forced Swimming Rat Experimental Model
by Ekaterina A. Korf, Artem V. Novozhilov, Igor V. Mindukshev, Andrey S. Glotov, Igor V. Kudryavtsev, Ekaterina V. Baidyuk, Irina A. Dobrylko, Natalia G. Voitenko, Polina A. Voronina, Samarmar Habeeb, Afrah Ghanem, Natalia S. Osinovskaya, Maria K. Serebryakova, Denis V. Krivorotov, Richard O. Jenkins and Nikolay V. Goncharov
Int. J. Mol. Sci. 2024, 25(19), 10438; https://doi.org/10.3390/ijms251910438 - 27 Sep 2024
Cited by 1 | Viewed by 1712
Abstract
The study of drugs of natural origin that increase endurance and/or accelerate recovery is an integral part of sports medicine and physiology. In this paper, decaffeinated green tea extract (GTE) and two ammonium salts—chloride (ACL) and carbonate (ACR)—were tested individually and in combination [...] Read more.
The study of drugs of natural origin that increase endurance and/or accelerate recovery is an integral part of sports medicine and physiology. In this paper, decaffeinated green tea extract (GTE) and two ammonium salts—chloride (ACL) and carbonate (ACR)—were tested individually and in combination with GTE as stimulants of physical performance in a forced swimming rat experimental model. The determined parameters can be divided into seven blocks: functional (swimming duration); biochemistry of blood plasma; biochemistry of erythrocytes; hematology; immunology; gene expression of slow- and fast-twitch muscles (m. soleus, SOL, and m. extensor digitorum longus, EDL, respectively); and morphometric indicators of slow- and fast-twitch muscles. Regarding the negative control (intact animals), the maximum number of changes in all blocks of indicators was recorded in the GTE + ACR group, whose animals showed the maximum functional result and minimum lactate values on the last day of the experiment. Next, in terms of the number of changes, were the groups ACR, ACL, GTE + ACL, GTE and NaCl (positive control). In general, the number of identified adaptive changes was proportional to the functional state of the animals of the corresponding groups, in terms of the duration of the swimming load in the last four days of the experiment. However, not only the total number but also the qualitative composition of the identified changes is of interest. The results of a comparative analysis suggest that, in the model of forced swimming we developed, GTE promotes restoration of the body and moderate mobilization of the immune system, while small doses of ammonium salts, especially ammonium carbonate, contribute to an increase in physical performance, which is associated with satisfactory restoration of skeletal muscles and the entire body. The combined use of GTE with ammonium salts does not give a clearly positive effect. Full article
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