Search Results (138)

Prenatal and postnatal skeletal muscle development in ruminants is coordinated by interactions between genetic, nutritional, epigenetic, and endocrine factors. This review focuses on the influence of maternal nutrition during gestation on fetal myogenesis, satellite cell dynamics, and myogenic regulatory factors expression, including MYF5, MYOD1, and MYOG. Studies in sheep and cattle indicate that nutrient restriction or overnutrition alters muscle fiber number, the cross-sectional area, and the transcriptional regulation of myogenic genes in offspring. Postnatally, muscle hypertrophy is primarily mediated by satellite cells, which are activated via PAX7, MYOD, and MYF5, and regulated through mechanisms such as CARM1-induced chromatin remodeling and miR-31-mediated mRNA expression. Hormonal signaling via the GH–IGF1 axis and thyroid hormones further modulate satellite cell proliferation and protein accretion. Genetic variants, such as myostatin mutations in Texel sheep and Belgian Blue cattle, enhance muscle mass but may compromise reproductive efficiency. Nutritional interventions, including the plane of nutrition, supplementation strategies, and environmental stressors such as heat and stocking density, significantly influence muscle fiber composition and carcass traits. This review provides a comprehensive overview of skeletal muscle programming in ruminants, tracing the developmental trajectory from progenitor cell differentiation to postnatal growth and maturation. These insights underscore the need for integrated approaches combining maternal diet optimization, molecular breeding, and precision livestock management to enhance muscle growth, meat quality, and production sustainability in ruminant systems. Full article

Skeletal muscle atrophy is a debilitating condition characterized by the loss of muscle mass and function. It is commonly associated with aging, chronic diseases, disuse, and prolonged glucocorticoid therapy. Oxidative stress and catabolic signaling pathways play significant roles in the progression of muscle degradation. Despite its clinical relevance, few effective therapeutic options are currently available. In this study, we investigated the protective effects of an ethanolic extract of Glycine Semen Preparata (GSP), i.e., fermented black soybeans, using in vitro and in vivo models of dexamethasone (Dexa)-induced muscle atrophy. In C2C12 myoblasts and myotubes, GSP significantly attenuated both oxidative stress-induced and Dexa-induced damages by reducing reactive oxygen species levels and by suppressing the expression of the muscle-specific E3 ubiquitin ligases MuRF1 and Atrogin-1. Moreover, GSP upregulated key genes involved in muscle regeneration (Myod1 and Myog) and mitochondrial biogenesis (PGC1α), indicating its dual role in muscle protection and regeneration. Oral administration of GSP to mice with Dexa-induced muscle atrophy resulted in improved muscle fiber integrity, increased proportion of large cross-sectional area fibers, and partial recovery of motor function. Isoflavone aglycones, such as daidzein and genistein, were identified as active compounds that contribute to the beneficial effects of GSP through antioxidant activity and gene promoter enhancement. Thus, GSP is a promising nutraceutical that prevents or mitigates muscle atrophy by targeting oxidative stress and promoting myogenesis and mitochondrial function. Further studies are warranted to standardize the bioactive components and explore their clinical applications. Full article

As life expectancy increases, muscle atrophy, characterized by a decline in muscle mass and strength that can impair mobility, has become a growing concern, highlighting the potential of protein supplementation as a promising intervention strategy. A horse meat hydrolysate, with a molecular weight of less than 3 kDa, derived from m. biceps femoris and produced using the food-grade enzyme Alcalase^® (A4 < 3kDa) was evaluated for its efficacy in mitigating dexamethasone-induced muscle atrophy, a widely accepted model for studying catabolic muscle loss. Administered orally to C57BL/6 mice at dosages of 200 mg/kg or 500 mg/kg body weight for 35 days, A4 < 3kDa effectively countered the weight loss induced by dexamethasone in the whole body, quadriceps, tibialis anterior, and gastrocnemius muscles. Moreover, it increased muscle fiber cross-sectional area and grip strength. These effects were attributed to increased protein synthesis via the protein kinase B (AKT)/forkhead box O3 (FoxO3a)/mammalian target of rapamycin (mTOR) signaling pathway. A4 < 3kDa augmented the phosphorylation of key components of the signaling pathways associated with muscle atrophy, resulting in reduced mRNA expression of Atrogin-1 and MuRF-1. These findings demonstrate the potential of A4 < 3kDa as a functional food ingredient for preventing muscle atrophy. Full article

Background/Objectives: Chestnut inner shells, traditionally used in Korean and Chinese herbal medicine, contain antioxidant and anti-inflammatory compounds that contribute to complementary medicine. This study aimed to explore the therapeutic effects of chestnut inner-shell extract (CIE) on skeletal muscle injury and atrophy using both in vivo and in vitro models. Methods: We used three experimental models representing distinct pathological mechanisms: (1) barium chloride (BaCl₂)-induced muscle injury to model acute myofiber damage, (2) sciatic nerve transection to model chronic neurogenic muscle atrophy, and (3) H₂O₂-treated C2C12 myoblasts to model oxidative-stress-related myogenic impairment. Histological analyses (e.g., hematoxylin and eosin staining and cross-sectional area measurement) and molecular analyses were performed to evaluate the effects of CIE on muscle structure, apoptosis, and oxidative stress. Results: In the BaCl₂ injury model, CIE treatment significantly restored the muscle fiber structure, with muscle protein levels returning to near-normal levels. In the denervation-induced muscle atrophy model, CIE treatment led to a dose-dependent decrease in apoptosis-related factors (especially cleaved caspase-3) and mitigated the Akt/mTOR signaling pathway. In the in vitro oxidative stress model, CIE suppressed the expression of NRF2 and HO-1, which are key oxidative stress response regulators. Conclusions: These findings suggest that CIE may offer therapeutic potential for mitigating skeletal muscle damage, atrophy, and oxidative stress. Full article

Age-related skeletal muscle atrophy is a major health concern in the elderly, contributing to reduced mobility, increased risk of falls, and metabolic dysfunction. The senescence-accelerated prone 8 (SAMP8) mouse model, known for its rapid aging and early cognitive decline, serves as an essential model for studying age-related muscle degeneration. While previous studies have shown that exercise attenuates muscle atrophy by promoting regeneration and improving strength, the underlying metabolic mechanisms remain poorly understood. This study used the SAMP8 model to evaluate the effects of exercise on muscle atrophy and associated metabolic changes. Our results show that exercise promoted muscle growth by reducing body weight, increasing skeletal muscle mass, and decreasing fat accumulation. Furthermore, exercise improved grip strength, muscle tone, and muscle fiber cross-sectional area, thereby preserving muscle functionality. NMR-based metabolomic analysis identified key metabolic pathways modulated by exercise, including glycine, serine, and threonine metabolism; alanine, aspartate, and glutamate metabolism; pyruvate metabolism; and taurine and hypotaurine metabolism. These findings underscore the therapeutic potential of exercise in combating age-related muscle wasting and elucidate the metabolic pathways underlying its benefits. Full article

Consumers are increasingly demanding higher-quality mutton. Crossbreeding has been recognized as an effective means to improve meat quality. However, the phenomenon underlying these molecular system mechanisms remains largely unidentified. In this study, 48 male lambs aged 3 months were selected, including ♂ Hu sheep × ♀ Hu (HH, n = 16), ♂ Polled Dorset × ♀ Hu sheep F₁ hybrid lambs (DH, n = 16), and ♂ Southdown × ♀ Hu sheep (SH, n = 16) F₁ hybrid lambs, and raised in a single pen under the same nutritional and management conditions for 95 days. Then, seven sheep close to the average weight of the group were selected and fasted for 12 h prior to slaughter. By comparing the muscle fiber characteristics of the Longissimus dorsi of the three groups of sheep, and through transcriptomic and metabolomic analyses, we revealed molecular differences in the meat quality of Hu sheep crossbred with different parent breeds. The results of this study showed that muscle fiber diameter and cross-sectional area were significantly greater in the DH group than in the HH group, and collagen fiber content in the DH group was also significantly higher than in the HH group (p < 0.05). A total of 163 differential genes and 823 differential metabolites were identified in the three groups, most of which were related to muscle development and lipid metabolism. These included the AMPK signaling pathway, the PI3K-Akt signaling pathway, glycerophospholipid metabolism, and the related genes EFHB, PER3, and PPARGC1A. The results of this study offer valuable insights into the molecular mechanisms underlying the impact of crossbreeding on meat quality and provide a theoretical foundation for sheep crossbreed production. Full article

Muscle atrophy leads to decreased muscle mass, weakness, inactivity, and increased mortality. E3 ubiquitin ligases, key regulators of protein degradation via the ubiquitin–proteasome system, play a critical role in atrophic mechanisms. This meta-analysis followed Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines, and its objective was to evaluate the association between E3 ligases Muscle Atrophy F-box (MAFbx)/Atrogin-1 (Fbxo32) and Muscle RING-finger protein 1 (MuRF-1) (TRIM63) E3 ligase mRNA levels, reductions in skeletal muscle CSA measures, and atrophy conditions. We examined papers published on PubMed^®, Scopus, and Web of Science that studied E3 ligase gene expression signatures for Fbxo32 (MAFbx/Atrogin-1) and Trim63 (MuRF1) in different types of muscle atrophy and hypertrophy murine models. Twenty-nine studies selected by two independent raters were analyzed. Standardized mean differences (SMDs)/effect sizes (ESs) and 95% confidence intervals (CIs) were calculated for the outcomes using fixed-effects models. We found that 6- and 4.8-fold upregulation, respectively, of Fbxo32 and Trim63 was sufficient to reduce the ES to −3.89 (95% CI: −4.45 to −3.32) for the muscle fiber cross-sectional area and the development of skeletal muscle atrophy. I² and Q test statistics did not indicate heterogeneous data. There was a low probability of bias after both the funnel plot and Egger’s test analyses. These results were sustained independently of the atrophic model and muscle type. Therefore, the magnitude of the increase in muscle Fbxo32 and Trim63 mRNA is a feasible, reliable molecular marker for skeletal muscle atrophy in mice. The next step for the Ubiquitin-proteasome system (UPS) field involves elucidating the targets of E3 ligases, paving the way for diagnostic and treatment applications in humans. Full article

We investigated the effects of belt electrode-skeletal muscle electrical stimulation (B-SES) on muscle atrophy in collagen-induced arthritis (CIA) rats. Twenty-eight 8-week-old male Dark Agouti rats were immunized with type II collagen and Freund’s incomplete adjuvant (day 0). From days 14 to 28, 18 rats received B-SES (50 Hz) four times only on the right hindlimb (STIM), while the contralateral left hindlimb remained unstimulated. Both hindlimbs of 10 untreated CIA rats were defined as controls (CONT). Paw volume was measured every other day. On day 28, the muscle weight, histology, and gene expression of the soleus and extensor digitorum longus (EDL) were analyzed. B-SES did not worsen paw volume throughout the experimental period. Compared with CONT, the muscle weight and fiber cross-sectional area of the soleus were higher in STIM. The expression of muscle degradation markers (atrogin-1 and MuRF-1) in the soleus and EDL was lower in the STIM group than that in the CONT group. In contrast, B-SES did not significantly affect the expression of muscle synthesis (Eif4e and p70S6K) and mitochondrial (PGC-1α) markers. B-SES prevents muscle atrophy in CIA rats by reducing muscle degradation without exacerbating arthritis, demonstrating its promising potential as an intervention for RA-induced muscle atrophy. Full article

Introduction and Aim: The beneficial effects of aerobic training (AT) on preventing excess fat mass, and of resistance training (RT) on skeletal muscle adaptation, are well established. However, the effects of concurrent training (CT) compared to AT or RT alone on body composition in middle-aged and older adults are less understood, and therefore, the focus of this meta-analysis. Methods: Three databases, including PubMed, Web of Science, and Scopus, were searched from inception to March 2024. Randomized trials were included if they compared CT versus either AT or RT, and included body composition measures such as fat mass, body fat percentage, waist circumference, visceral fat mass, lean body mass (LBM), muscle mass/volume, or muscle or muscle fiber cross-sectional area (CSA), in middle-aged (50 to <65 years) and older adults (≥65 years). Weighted mean differences (WMD) or standardized mean differences (SMD) and 95% confidence intervals (CIs) were calculated using random effects models. Results: A total of 53 studies involving 2873 participants were included. Overall, CT increased body weight and LBM significantly more, trending toward significantly larger increases in muscle mass and CSA, compared with AT alone. However, there were no significant differences between CT and RT alone, for body weight, BMI, body fat percentage, fat mass, waist circumference, or visceral fat mass. Conclusions: CT is as effective as AT for decreasing body fat measures and as effective as RT for increasing muscle mass in middle-aged and older adults, and it should be recommended accordingly. Full article

The present study aimed to investigate the correlation between muscle fiber type variables and sprinting, jumping, strength, power and endurance performances in sprinters and marathon runners. Furthermore, the study explored which muscle fiber type variable influences athletes’ performance the most and which variable discriminates sprinters from marathon runners. Body composition, vastus lateralis muscle fiber composition, sprinting, jumping, strength, maximum isometric force, rate of force development and endurance performance were assessed in well-trained sprinters (n = 15; age: 24.7 ± 4.1 years; body mass: 82.7 ± 8.8 kg; body fat: 11.3 ± 4.2%) and marathon runners (n = 15; age: 26.1 ± 3.2 years; body mass: 69.7 ± 4.3 kg; body fat: 9.5 ± 3.3%). Significant correlations were observed between muscle fiber composition variables and performances (r = −0.848 to 0.902; p < 0.05), with percentage cross-sectional areas (%CSAs) showing the strongest associations. Regression analyses confirmed %CSAs as the strongest predictors of performance (R²: 0.796–0.978; p < 0.001; B coefficients: −0.293–0.985), while discriminant analysis accurately differentiated sprinters from marathon runners (100%, p < 0.001) by only using athletes’ muscle fibers’ %CSAs. In conclusion, muscle fibers’ %CSAs may be the most critical variables for explaining and distinguishing sprinters’ and marathon runners’ performances. Full article

Background: The gradual rise in global temperatures can affect skeletal muscle development and intestinal microorganisms. However, the influence of microbial metabolites on skeletal muscle homeostasis under heat stress (HS) remains unclear. Methods: C57BL/6J mice were exposed to normal temperature or 40 °C conditions for 3 d, 7 d, or 14 d. The HS 7 d mice also were treated with sodium butyrate (NaB, 200 mg/kg, gavage). Results: Strikingly, the body weight, antioxidative ability (MDA, T-SOD, and GSH-Px), and average cross-sectional area decreased, but the blood glucose and core temperature increased under HS. However, the NaB treatment reversed these effects. Meanwhile, HS also increased the levels of TNF-α and CORT. Additionally, HS led to a reduction in the villus height and an increase in the crypt depth of the intestine. Microbial 16S rRNA sequencing analysis revealed that HS caused gut microbiota dysbiosis. NaB increased the expression of HSP70 under HS, to maintain skeletal muscle homeostasis. HS stimulated the expression of Pax7, which indicates that skeletal muscle homeostasis was disrupted. Meanwhile, the expressions of MyoG and MyoD were decreased under HS. The immunofluorescence results also show that HS triggered a shift from slow muscle fibers (MYH7) to fast muscle fibers (MYH1). However, NaB recovered the expressions of these muscle-related factors. HS inhibited autophagy initiation (mTOR, Beclin1, Atg5, Atg7, and Atg12), the formation (LC3 II/LC3 I) of autophagosomes, and the binding (p62 and LAMP1) of lysosomes to autophagosomes, which were activated by NaB. C2C12 cells were treated with H₂O₂ to simulate skeletal muscle oxidative stress, and treated with NaB in advance. Oxidative stress disrupted the homeostasis of the C2C12 cells, characterized by an increase in Pax 7 and decreases in MyoG and MyoD, but these changes were reversed by the NaB treatment. Meanwhile, NaB was unable to maintain the stable expression of Pax7 when autophagy was inhibited. Conclusions: This suggests that NaB can regulate oxidative stress induced by HS through autophagy to maintain skeletal muscle homeostasis. Full article

The chemotherapeutic agent doxorubicin (DOX) leads to the loss of skeletal muscle and adipose tissue mass, contributing to cancer cachexia. Experimental research on the molecular mechanisms of long-term DOX treatment is modest, and its effect on both skeletal muscle and adipose tissue has not been studied in an integrative manner. Dexrazoxane (DEXRA) is used to prevent DOX-induced cancer-therapy-related cardiovascular dysfunction (CTRCD), but its impact on skeletal muscle and adipose tissue remains elusive. Therefore, this study aimed to investigate the long-term effects of DOX on adipose tissue and skeletal muscle metabolism, and evaluate whether DEXRA can mitigate these effects. To this end, 10-week-old male C57BL6/J mice (n = 32) were divided into four groups: (1) DOX, (2) DOX-DEXRA combined, (3) DEXRA and (4) control. DOX (4 mg/kg weekly) and DEXRA (40 mg/kg weekly) were administered intraperitoneally over 6 weeks. Indirect calorimetry was used to assess metabolic parameters, followed by a molecular analysis and histological evaluation of skeletal muscle and adipose tissue. DOX treatment led to significant white adipose tissue (WAT) loss (74%) and moderate skeletal muscle loss (Gastrocnemius (GAS): 10%), along with decreased basal activity (53%) and energy expenditure (27%). A trend toward a reduced type IIa fiber cross-sectional area and a fast-to-slow fiber type switch in the Soleus muscle was observed. The WAT of DOX-treated mice displayed reduced Pparg (p < 0.0001), Cd36 (p < 0.0001) and Glut4 (p < 0.05) mRNA expression—markers of fat and glucose metabolism—compared to controls. In contrast, the GAS of DOX-treated mice showed increased Cd36 (p < 0.05) and Glut4 (p < 0.01), together with elevated Pdk4 (p < 0.001) mRNA expression—suggesting reduced carbohydrate oxidation—compared to controls. Additionally, DOX increased Murf1 (p < 0.05) and Atrogin1 (p < 0.05) mRNA expression—markers of protein degradation—compared to controls. In both the WAT and GAS of DOX-treated mice, Ppard mRNA expression remained unchanged. Overall, DEXRA failed to prevent these DOX-induced changes. Collectively, our results suggest that DOX induced varying degrees of wasting in adipose tissue and skeletal muscle, driven by distinct mechanisms. While DEXRA protected against DOX-induced CTRCD, it did not counteract its adverse effects on skeletal muscle and adipose tissue. Full article

Collagen I is the most abundant type of intramuscular collagen. Lysyl oxidase promotes collagen cross-link formation, which helps stabilize the extracellular matrix. Furthermore, matrix metalloproteinases, responsible for collagen degradation, maintain typical muscle structure and function through remodeling. Although it is well known that aging leads to delayed recovery of muscle fibers, the impact of aging on the remodeling of intramuscular collagen is not well understood. In this study, we investigated the impact of aging on collagen remodeling during muscle injury recovery using young and old mouse models. Muscle injury was induced in the right tibialis anterior (TA) muscle of male C57BL/6J mice [aged 21 weeks (young) and 92 weeks (old)] using intramuscular cardiotoxin injection, with the left TA serving as a sham with saline injection. Following a one-week recovery period, aging was found to delay the recovery of the fiber cross-sectional area. The intensity and area of immunoreactivity for collagen I were significantly increased in old mice compared to young mice post-injury. Additionally, Lox expression and the number of LOX (+) cells in the extracellular matrix significantly increased in old mice compared to young mice post-injury. Furthermore, Mmp9 and MMP9 expression levels after muscle injury were higher in old mice than in young mice. These results suggest that muscle injury in old mice can lead to increased collagen I accumulation, enhanced collagen cross-link formation, and elevated MMP9 expression compared to young mice. Full article

Type 2 diabetes mellitus (T2DM) is a common metabolic disease that is frequently accompanied by multiple complications, including diabetic myopathy, a muscle disorder that is mainly manifested as decreased muscle function and reduced muscle mass. Diabetic myopathy is a relatively common complication among patients with diabetes that is mainly attributed to mitochondrial dysfunction. Therefore, we investigated the mechanisms underlying diabetic myopathy development, focusing on the role of microRNAs (miRs). Zebrafish were fed a high-sugar diet for 8 weeks and immersed in a glucose solution to establish a model of T2DM. Notably, the fish exhibited impaired blood glucose homeostasis, increased lipid accumulation in the skeletal muscles, and decreased insulin levels in the skeletal muscle. Additionally, we observed various symptoms of diabetic myopathy, including a decreased cross-sectional area of skeletal muscle fibers, increased skeletal muscle fibrosis, a significant decline in exercise capacity, and a significant decrease in mitochondrial respiratory function. Mechanistically, bioinformatic analysis combined with various molecular analyses showed that the miR-139-5p/NAMPT pathway was involved in long-term high-glucose-induced mitochondrial dysfunction in the skeletal muscle, leading to diabetic myopathy. Conclusively, this study provides a basis for the development of novel strategies for the prevention and treatment of diabetic myopathy. Full article

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