The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensi...The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensional chromatin architecture of skeletal muscle development has not been studied intensively although dynamic transcriptional regulation during differentiation of muscle cells is one of the most deeply studied processes.The RNA-seq was used to analyze the transcriptome pattern during chicken muscle development across 12 stages.Hi-C was used to build chromatin architectures during four representative stages.Ch IP-seq was conducted to identify enhancers and promoters in these four stages,which are occupied by histone H3K27ac and H3K4me3 peaks.Results show that large-scale genome architecture changes are mostly unidirectional,and coupled by complex on/off dynamic patterns of gene expression.Specifically,we observed 258.30 Mb of the genome undergoing A/B compartment switching.Notable alterations(316.57 Mb)of interaction frequencies within TADs were observed.Substantial aging-associated genes exhibited ascending connectivity with the compartment transition from repressive to active status during muscle development.Some muscle-related gene promoters that interacted with active enhancers during development,and some myopathy/aging-associated genes that were activated in aging muscle were founded.These results provide key insights into skeletal muscle development in vivo,and offer a valuable resource that allows in-depth functional characterization of candidate genes.展开更多
Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in thi...Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in this process.Methods: 8-week-old male C57BL/6J mice were carried out combined exercise for 10 weeks. One week before the end of the intervention, mice underwent cast immobilization. Additionally, to investigate the potential mechanism in exercise-induced protection of skeletal muscle, mice in the exercise preconditioning group were administered TC-E-5003(an inhibitor of Prmt1 enzymatic activity). Exercise performance, muscle mass, and the cross-sectional area(CSA) of muscle fibers were analyzed. Besides, Prmt1 and Sestrin1(Sesn1) were either overexpressed or inhibited in C2C12 myotubes to elucidate the underlying mechanism.Results: Exercise preconditioning not only significantly improved muscle mass and motor ability in immobilized mice but also inhibited excessive activation of degradation pathways and enhanced protein synthesis. Importantly, Prmt1 mediated the protective effects of exercise preconditioning on muscle atrophy. Mechanistically,Prmt1 regulated the p38 mitogen-activated protein kinase(p38)/activating transcription factor 2(ATF2)pathway, which modulates Sesn1 expression. Sesn1 acts as a downstream of Prmt1 and ATF2, contributing to the myoblast differentiation and skeletal muscle regeneration through AMP-Activated protein kinase α2(AMPKα2)/transcriptional co-activator PPAR-γ co-activator-1 α(PGC-1α) signaling pathway.Conclusions: Taken together, our results highlighted the effectiveness of exercise preconditioning in preventing muscle atrophy via the Prmt1-Sesn1 pathway.展开更多
Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reti...Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.展开更多
To perform various functions in the body,skeletal muscle is controlled and coordinated as a whole by nerves.However,there has been little research into whether the nerve control characteristics of different muscles ar...To perform various functions in the body,skeletal muscle is controlled and coordinated as a whole by nerves.However,there has been little research into whether the nerve control characteristics of different muscles are different,and the importance of these potential differences.In the present study,we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles.We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways.In terms of spatial distribution patterns,sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons.In addition,the neuronal innervation of limb muscles exhibited four different characteristics:sympathetic neuron-rich muscle,sensory neuron-rich muscle,neuron-sparse muscle,and motor neuron-rich muscle.Sensory neuron density was mainly associated with muscle contractile structure and cell pH,whereas sympathetic neuron density was associated with protein kinase activity,muscle vasculature,muscle calcium-dependent protein kinase activity,lipid transport,and vesicle release.Motor neuron density was mainly associated with protein kinase activity,cell adhesion,oxidoreductase activity,and exocytosis.These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions,thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.展开更多
Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-in...Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.展开更多
Sarcomerogenesis,the addition of serial sarcomeres in skeletal muscle myofibrils and fibres,is a natural occurrence during growth and maturation of animals,including humans.However,the detailed mechanisms that allow f...Sarcomerogenesis,the addition of serial sarcomeres in skeletal muscle myofibrils and fibres,is a natural occurrence during growth and maturation of animals,including humans.However,the detailed mechanisms that allow for sarcomerogenesis are not fully understood.In some diseases,such as cerebral palsy in children,sarcomerogenesis appears to be inhibited or at least reduced,1,2 often causing severe restrictions in muscle and joint function.展开更多
BACKGROUND Improving our understanding of whether increased dietary intake ofω-3 polyunsaturated fatty acids(PUFAs)is beneficial for increasing skeletal muscle mass in patients with metabolic dysfunction-associated f...BACKGROUND Improving our understanding of whether increased dietary intake ofω-3 polyunsaturated fatty acids(PUFAs)is beneficial for increasing skeletal muscle mass in patients with metabolic dysfunction-associated fatty liver disease(MAFLD)could provide an important clinical evidence base for the development of relevant nutritional guidelines.AIM To investigate the effect of total dietaryω-3 PUFAs and their subtypes on skeletal muscle mass in MAFLD.METHODS This cross-sectional study involved 2316 participants from four National Health and Nutrition Examination Survey cycles between 2011 and 2018.Dietary intake ofω-3 PUFAs was collected through 24-hour dietary recall interviews.Appendicular skeletal muscle mass index(ASMI)was calculated by dividing ASM in kilograms by height squared.RESULTS The multiple linear regression model showed significant relationships for dietary intake of totalω-3 PUFAs with higher ASMI(β:0.06,95%CI:0.01-0.11)in MAFLD patients.Dietary a-linolenic acid(ALA)(β:0.06,95%CI:0.01-0.12),docosapentaenoic acid(β:1.28,95%CI:0.01-2.54),and docosahexaenoic acid(DHA)(β:0.19,95%CI:0.01-0.37)were significantly associated with higher ASMI,while intake of stearidonic acid and eicosapentaenoic acid did not improve ASMI.In patients with high probability of liver fibrosis,dietary intake of ALA was associated with higher ASMI(β:0.11,95%CI:0.03-0.18).Stratified analysis found that DHA was associated with higher ASMI in patients with obesity and higher metabolic risk.CONCLUSION Increasing dietary intake ofω-3 PUFAs improved skeletal muscle health in patients with MAFLD.Patient with obesity and higher metabolic risk were more likely to benefit from intake of DHA.展开更多
Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be el...Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.展开更多
Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,d...Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,disrupting proteostasis and increasing vulnerability to sarcopenia.High-intensity training(HIT)can counteract these declines by activating protective pathways such as the HSP response.HSPs are highly responsive to stress,examining their regulation during aging is important,as altered HSP activity is linked to the progressive loss of muscle mass.Methods This study investigated the abundance and phosphorylation of HSPs in skeletal muscle from healthy,active young and older adults(n=7 per group),assessed at baseline and again in the older group following 12 weeks of HIT.Using calibrated Western blotting on both whole-muscle homogenates and pooled single muscle fibres,we quantified HSP content and phosphorylation to determine how aging and exercise influence stress–responsive protein regulation at both the tissue and cellular levels.Results In whole muscle homogenates,HSPs(HSP72,HSP27,andαB-crystallin)did not differ between young and older adults,while higher phosphorylation of small HSPs(sHSPs):phospho-HSP27 at Serine15(pHSP27 Ser15)and phospho-αB-crystallin at Serine59(pαB-crystallin Ser59)(∼1.8-fold and∼2.9-fold,respectively)were found in muscle from older adults,indicating higher cellular stress associated with aging.A 12-week HIT intervention in older adults reduced homogenate pHSP27 Ser15 and pαB-crystallin Ser59 abundances to similar levels found in young adults.Total HSPs typically displayed a distinct fiber-type profile in both age groups,with more in type I compared to type II fibers,distinguished by the presence of myosin heavy chain I(MHCI)or MHCII.Phosphorylation at pHSP27 Ser15 and pαB-crystallin Ser59 was not different between type I and type II fibers.The HIT in older adults decreased total and phosphorylated sHSPs in both type I and type II fibers but increased HSP72 in type I fibers.Conclusion HIT has the potential to mitigate age-related cellular stress and modulate protein expression patterns in aging skeletal muscle and,perhaps,has the potential to delay age-related muscle decline,thereby improving muscle health in older adults.展开更多
Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to su...Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to sustain BCAAs releasing rate may facilitate muscle protein synthesis.To examine this hypothesis,we conducted a series of protein supplements including modified slow-digesting whey(SDW),whey,hydrolyzed whey and casein,orally to mice undergoing endurance running.Our results showed that the SDW gavage constant supplied BCAAs in the serum of mice within 6 h and significantly enhanced(P<0.01)endurance exercise capacity,compared to other groups.In addition,the SDW supplementation increased the crosssectional area of mice gastrocnemius fibers,as well as their muscle and liver glycogen content.It also increased the testosterone/cortisol ratio in serum and interleukin-6(IL-6)levels in muscle,while it decreased the tumor necrosis factor-alpha(TNF-α)levels and oxidative stress in muscle.Moreover,it may activate mechanistic target of rapamycin signaling by upregulating mRNA(bcat-1 and pgc-1α)expression.Thus,our findings illustrate that prolonged BCAAs supply duration promotes mice endurance running capacity and skeletal muscle growth,contributing to the advancement of sports nutrition practices.展开更多
Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease(COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathw...Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease(COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy-and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.展开更多
1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site o...1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site of insulin resistance,with impaired insulin signaling and reduced glucose transport activity contributing to metabolic dysfunction.展开更多
Background While maternal proline(Pro)supplementation has demonstrated efficacy in enhancing placental angiogenesis and farrowing efficiency in swine,its regulatory role in fetal skeletal muscle ontogeny remains undef...Background While maternal proline(Pro)supplementation has demonstrated efficacy in enhancing placental angiogenesis and farrowing efficiency in swine,its regulatory role in fetal skeletal muscle ontogeny remains undefined.This study systematically evaluated the temporal-specific impacts of dietary Pro supplementation during critical phases of fetal myogenesis(encompassing primary myofiber formation and secondary myofiber hyperplasia)on offspring muscle development.A total of 120 sows with similar farrowing schedules were assigned to three groups:CON(basal diet),ST-Pro(0.5%Pro supplementation during secondary myofiber formation period,from d 60 gestation to farrowing),LT-Pro(0.5%Pro supplementation spanning primary and secondary myofiber formation period:from d 20 gestation to farrowing).Results LT-Pro group significantly increased the longissimus dorsi(LD)muscle mass per unit body weight in newborn piglets compared to CON group(P<0.05),while no such effect was observed in the ST-Pro group.Metabolomic profiling revealed elevated Pro,lysine,and tryptophan levels in the LD muscle of LT-Pro group piglets,accompanied by reduced branched-chain amino acids(BCAAs;leucine,isoleucine,and valine)in both serum and muscle(P<0.05).Histological analysis demonstrated a 45.74%increase in myofiber cross-sectional area in the LT-Pro group(P<0.05).At the molecular level,LT-Pro group piglets exhibited upregulated mRNA expression levels of myogenic regulatory genes(MYOD1,MYF6)and the cell cycle accelerator CCND1(P<0.05),coupled with activation of the STAT3 signaling pathway(phosphorylated STAT3 protein increased by 2.53-fold,P<0.01).Furthermore,Pro supplementation enhanced oxidative metabolism,evidenced by elevated mitochondrial biogenesis markers(the mRNA expression levels of PPARGC1A,OPA1,and SQSTM1)and a 61.58%increase in succinate dehydrogenase activity(P<0.05).Notably,LT-Pro group piglets showed a selective shift toward slow-twitch oxidative fibers,with both MyHC1 mRNA and protein expression levels significantly upregulated(P<0.05),while the mRNA expression levels of MyHCIIb showed no significant change.Conclusions This study identified the primary fiber formation period as a critical window.Supplementation with Pro during G20–114 reprogrammed offspring skeletal muscle development through STAT3-CCND1-mediated myoblast proliferation,enhanced mitochondrial bioenergetics,and oxidative fiber specification.However,no such effects were observed during G60–114.These findings propose maternal Pro intervention as a novel strategy to enhance muscle yield and metabolic efficiency in swine production,with potential applications for improving meat quality traits linked to oxidative muscle phenotypes.展开更多
Pneumatic artificial muscles(PAMs)can generate multimodal movements,e.g.,linear contraction/extension,spiral torsion,and bending motions.Among these motions,contraction and extension movements can be achieved using li...Pneumatic artificial muscles(PAMs)can generate multimodal movements,e.g.,linear contraction/extension,spiral torsion,and bending motions.Among these motions,contraction and extension movements can be achieved using linear PAMs(LPAMs)designed to mimic human skeletal muscle.LPAMs have considerable potential for wearable applications and can be integrated into soft wearable robotic systems.Due to their inherent compliance,excellent human-robot interaction,safety,and low cost,LPAMs are considered potential alternatives as actuator components in the construction of wearable robots.This review presents a comprehensive overview of the bio-inspired design of LPAMs and their wearable applications.The biomechanics of human skeletal muscle,including anatomy,morphology,and biomechanical characterization,is analyzed to provide design inspirations for LPAMs and determine the assistance requirements of LPAM-based wearable robots.Herein,LPAMs are classified into four categories based on their structural shapes,including cylindrical-shaped muscles,flat-shaped muscles,fold-shaped muscles,and muscles with other shapes.In addition,this review provides an overview of the diverse physical interfaces utilized in wearable robots and presents a comparative analysis of the actuation characteristics of LPAMs and the assistance performance of LPAM-based wearable robots.This analysis was conducted in consideration of several key metrics,including the contraction ratio,maximum force,specific force,response frequency,assistive torque/bodyweight,and net metabolic cost.Finally,this review summarizes the ongoing challenges and future research directions.展开更多
Metabolic dysfunction-associated steatotic liver disease is increasingly understood to be closely linked with skeletal muscle alterations,such as sarcopenia,myoste-atosis,and metabolic dysregulation,which play a key r...Metabolic dysfunction-associated steatotic liver disease is increasingly understood to be closely linked with skeletal muscle alterations,such as sarcopenia,myoste-atosis,and metabolic dysregulation,which play a key role in its pathogenesis and progression.Recent literature,including an article by Isakov,highlights the bidirectional interactions between muscle and liver,underscoring shared mechanisms such as insulin resistance,inflammation,and myokine imbalance.This letter reflects on key findings from the review,noting strengths such as its integration of mechanistic insights,discussion of emerging biomarkers,and emphasis on lifestyle and pharmacological interventions.It also identifies areas for further development,including standardization of diagnostic criteria and more rigorous evaluation of translational data.As muscle health gains promi-nence in metabolic dysfunction-associated steatotic liver disease research,multidisciplinary strategies that target both hepatic and muscular systems may offer more effective avenues for prevention and treatment.展开更多
Background: Aging-induced cardiac hypertrophy and reduced skeletal muscle strength contribute to increased disease risk and life burden in the elderly. FNDC5 acts as a protective muscle factor in both cardiac and skel...Background: Aging-induced cardiac hypertrophy and reduced skeletal muscle strength contribute to increased disease risk and life burden in the elderly. FNDC5 acts as a protective muscle factor in both cardiac and skeletal muscle. This study aims to examine the relationship between cardiac FNDC5 and aging-related cardiac hypertrophy and decreased skeletal muscle strength. Methods: Male young C57BL/6 mice (5 months old, n = 6) and aged mice (21 months old, n = 6) were utilized in the study and housed in a specific pathogen-free (SPF) environment. Prior to the experiment, grip strength tests were performed on the mice, and heart tissues were collected for morphological analysis, including the assessment of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and fibronectin type III-containing structural domain 5 (FNDC5) protein levels. Furthermore, myosin heavy chain II (MyHC II), skeletal muscle-specific transcription factor (MyoD), muscle RING-finger protein-1 (MuRF1), and FNDC5 levels were evaluated in the quadriceps muscle. The correlations between heart weight and FNDC5 expression levels, as well as skeletal muscle indices in the mice, were subsequently analyzed. Result: Aging leads to cardiac hypertrophy and reduced expression of PGC-1α and FNDC5 proteins. Concurrently, there is a decline in the strength of skeletal muscle, along with decreased expression of MyHC II and increased expression of MURF1 and MyoD. Correlation analysis demonstrated strong positive associations between myocardial FNDC5 protein levels and limb grip strength, as well as MyHC II, and strong negative associations with MyoD and MuRF1. Conclusion: There may be a significant association between aging-induced cardiac hypertrophy and decreased skeletal muscle strength, with FNDC5 potentially playing a crucial role as a regulatory molecule facilitating communication between the heart and skeletal muscle.展开更多
BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in the...BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.展开更多
Highland barley tea(HBT)is made from roasted barley seeds and is abundant inβ-glucan,amino acids,minerals,phenolics,and other natural active ingredients.These natural compounds found in whole grains have been shown t...Highland barley tea(HBT)is made from roasted barley seeds and is abundant inβ-glucan,amino acids,minerals,phenolics,and other natural active ingredients.These natural compounds found in whole grains have been shown to slow aging and positively affect skeletal muscle function.As a result,studying the effects of HBT on the skeletal muscle health of the elderly population is critical from a scientific and societal standpoint for improving their health status and reducing the medical burden on society.The antioxidant activity and the content of natural active substances were used as indicators to screen the optimal process of HBT brewing.The effects of long-term HBT consumption on aging in mice were investigated by using HBT as a substitute for drinking water in naturally aging mice for a 5-month intervention.Afterward,various factors were measured,such as basic physiological indices,inflammation,plasma metabolites,skeletal muscle function,and exercise capacity,to evaluate the effects of HBT on aging in mice.Long-term consumption of HBT reduced body and spleen weight,increased body weight percentage of skeletal muscle,and reduced plasma inflammation levels in aging mice.Metabolomic results showed increased plasma levels of the mitochondrial marker short-chain acylcarnitine and some amino acids.Additionally,there was a decrease in bile and long-chain acylcarnitine.The level of fibrosis in the gastrocnemius muscle of aging mice was suppressed,and the percentage of typeⅠmuscle fibers was increased,improving the endurance of the mice.Thus,long-term consumption of HBT may reduce body weight and increase skeletal muscle mitochondrial activity and exercise capacity in aging mice by reducing inflammation levels and alleviating mitochondrial damage.展开更多
Skeletal muscle satellite cells are stem cells characterized by their multipotency and capacity for in vitro proliferation.However,primary skeletal muscle satellite cells demonstrate limited proliferative capacity in ...Skeletal muscle satellite cells are stem cells characterized by their multipotency and capacity for in vitro proliferation.However,primary skeletal muscle satellite cells demonstrate limited proliferative capacity in vitro,which impedes their investigation in poultry skeletal muscle research.Cell immortalization techniques have emerged as valuable tools to address this limitation and facilitate the study of skeletal muscle satellite cell functions.This study achieved the immortalization of chicken skeletal muscle satellite cells through the transduction of primary cells with TERT(telomerase reverse transcriptase)amplified from chicken(chTERT)using a lentiviral vector via telomerase activity reconstitution.While the cells successfully overcame replicative senescence,complete immortalization was not achieved.Initial functional characterization revealed that the proliferative properties and cell cycle characteristics of the immortalized chicken skeletal muscle satellite cell lines(ICMS)closely resembled those of chicken primary muscle satellite cells(CPMSCs).Serum dependency analysis and soft agar assays confirmed that ICMS did not undergo malignant transformation.Furthermore,induced differentiation experiments demonstrated preserved differentiation capacity in ICMS.The established cell lines provide a fundamental framework for developing immortalized poultry cell lines and offer a cellular model for investigating poultry skeletal muscle-related functional genes.展开更多
BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and progno...BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.展开更多
基金supported by the National Key R&D Program of China(2023YFD1300040 and 2022YFF1000100)the Sichuan Science and Technology Program,China(2022NSFSC0132,2021YFYZ0009 and 2022JDJQ0054)the National Natural Science Foundation of China(32225046)。
文摘The development of skeletal muscle are complicated processes involving genes responsible for proper muscle morphology,contractility,cell proliferation,differentiation,interactions,migration,and death.The three-dimensional chromatin architecture of skeletal muscle development has not been studied intensively although dynamic transcriptional regulation during differentiation of muscle cells is one of the most deeply studied processes.The RNA-seq was used to analyze the transcriptome pattern during chicken muscle development across 12 stages.Hi-C was used to build chromatin architectures during four representative stages.Ch IP-seq was conducted to identify enhancers and promoters in these four stages,which are occupied by histone H3K27ac and H3K4me3 peaks.Results show that large-scale genome architecture changes are mostly unidirectional,and coupled by complex on/off dynamic patterns of gene expression.Specifically,we observed 258.30 Mb of the genome undergoing A/B compartment switching.Notable alterations(316.57 Mb)of interaction frequencies within TADs were observed.Substantial aging-associated genes exhibited ascending connectivity with the compartment transition from repressive to active status during muscle development.Some muscle-related gene promoters that interacted with active enhancers during development,and some myopathy/aging-associated genes that were activated in aging muscle were founded.These results provide key insights into skeletal muscle development in vivo,and offer a valuable resource that allows in-depth functional characterization of candidate genes.
基金funded by research grants from the National Natural Science Foundation of China (32171135 and 32371168)。
文摘Purpose: This study aimed to explore the effects of a 10-week combined exercise regimen on immobilizationinduced muscle atrophy and elucidate the possible function of Protein arginine methyltransferase 1(Prmt1) in this process.Methods: 8-week-old male C57BL/6J mice were carried out combined exercise for 10 weeks. One week before the end of the intervention, mice underwent cast immobilization. Additionally, to investigate the potential mechanism in exercise-induced protection of skeletal muscle, mice in the exercise preconditioning group were administered TC-E-5003(an inhibitor of Prmt1 enzymatic activity). Exercise performance, muscle mass, and the cross-sectional area(CSA) of muscle fibers were analyzed. Besides, Prmt1 and Sestrin1(Sesn1) were either overexpressed or inhibited in C2C12 myotubes to elucidate the underlying mechanism.Results: Exercise preconditioning not only significantly improved muscle mass and motor ability in immobilized mice but also inhibited excessive activation of degradation pathways and enhanced protein synthesis. Importantly, Prmt1 mediated the protective effects of exercise preconditioning on muscle atrophy. Mechanistically,Prmt1 regulated the p38 mitogen-activated protein kinase(p38)/activating transcription factor 2(ATF2)pathway, which modulates Sesn1 expression. Sesn1 acts as a downstream of Prmt1 and ATF2, contributing to the myoblast differentiation and skeletal muscle regeneration through AMP-Activated protein kinase α2(AMPKα2)/transcriptional co-activator PPAR-γ co-activator-1 α(PGC-1α) signaling pathway.Conclusions: Taken together, our results highlighted the effectiveness of exercise preconditioning in preventing muscle atrophy via the Prmt1-Sesn1 pathway.
文摘Skeletal muscle health and function are essential determinants of metabolic health,physical performance,and overall quality of life.The quality of skeletal muscle is heavily dependent on the complex mitochondrial reticulum that contributes toward its unique adaptability.It is now recognized that mitochondrial perturbations can activate various innate immune pathways,such as the nucleotide-binding oligomerization domain(NOD)-like receptor protein 3(NLRP3)inflammasome complex by propagating inflammatory signaling in response to damage-associated molecular patterns(DAMPs).The NLRP3 inflammasome is a multimeric protein complex and is a prominent regulator of innate immunity and cell death by mediating the activation of caspase-1,pro-inflammatory cytokines interleukin-1βand interleukin-18 and pro-pyroptotic protein gasdermin-D.While several studies have begun to demonstrate the relationship between various mitochondrial DAMPs(mtDAMPs)and NLRP3 inflammasome activation,the influence of various metabolic states on the production of these DAMPs and subsequent inflammatory profile remains poorly understood.This narrative review aimed to address this by highlighting the effects of skeletal muscle use and disuse on mitochondrial quality mechanisms including mitochondrial biogenesis,fusion,fission and mitophagy.Secondly,this review summarized the impact of alterations in mitochondrial quality control mechanisms following muscle denervation,aging,and exercise training in relation to NLRP3 inflammasome activation.By consolidating the current body of literature,this work aimed to further the understanding of innate immune signaling within skeletal muscle,which can highlight areas for future research and therapeutic strategies to regulate NLRP3 inflammasome activation during divergent metabolic conditions.
基金supported by the National Natural Science Foundation of China,No.82072162(to XY).
文摘To perform various functions in the body,skeletal muscle is controlled and coordinated as a whole by nerves.However,there has been little research into whether the nerve control characteristics of different muscles are different,and the importance of these potential differences.In the present study,we used a three-dimensional imaging of solvent-cleared organ-compatible multi-tracer technique to explore the spatial distribution patterns of sensory and sympathetic neurons that innervate limb muscles.We integrated transcriptome sequencing datasets from mouse limb muscles in public databases and performed correlation analysis with neuronal spatial distribution data to reveal the unique effects of different types of neurons on muscle functional pathways.In terms of spatial distribution patterns,sympathetic neurons exhibited a more concentrated distribution than sensory and motor neurons.In addition,the neuronal innervation of limb muscles exhibited four different characteristics:sympathetic neuron-rich muscle,sensory neuron-rich muscle,neuron-sparse muscle,and motor neuron-rich muscle.Sensory neuron density was mainly associated with muscle contractile structure and cell pH,whereas sympathetic neuron density was associated with protein kinase activity,muscle vasculature,muscle calcium-dependent protein kinase activity,lipid transport,and vesicle release.Motor neuron density was mainly associated with protein kinase activity,cell adhesion,oxidoreductase activity,and exocytosis.These findings may contribute to a deeper understanding of how nerves cooperate to endow muscles with diverse physiological functions,thereby providing new insights and experimental evidence for the treatment of various neuromuscular diseases.
基金supported by grants from the Knut and Alice Wallenberg foundation(P-OB,JRZ,and AK)the Swedish Research Council(JRZ and AK),Centrum för idrottsforskning(AK and JRZ)+7 种基金the NovoNordisk Foundation Metabolic Stress Associated Molecules(MSAM)consortium NNF15SA0018346 and Metabolite-related Inflammation and Disease(MeRIAD)consortium Grant number 0064142(AK)the Swedish Diabetes Foundation(AK and JRZ)the European Foundation for the Study of Diabetes(JRZ and AK)the Region Stockholm(ALF project)(JRZ and KC)the Strategic Research Program in Diabetes at Karolinska Institutet(JRZ and AK)supported by the Strategic Research Programme in Diabetes(SRP Diabetes)for use of the Seahorse flux analyzer.Human islets were made possible through the Juvenile Diabetes Research Foundation(JDRF)award 31-2008-416(European Coordinating Infrastructure for Islet Transplantation(ECIT),Islet for Basic Research program)AK holds a Distinguished Investigator Grant within Endocrinology and Metabolism from the Novo Nordisk Foundation(NNF24OC0088739)JRZ received the 2024 European Association for the Study of Diabetes(ESAD)-Novo Nordisk Foundation Diabetes Prize for Excellence(NNF24SA0092609).
文摘Background Regular physical training induces adaptive effects across multiple organ systems,highlighting the existence of inter-organ communication networks.However,the molecular mechanisms underlying both exercise-induced adaptations and organ-to-organ signaling are not fully characterized.Circulating extracellular vesicles(EVs),including exosomes,carry molecules like microRNAs(miRNAs)that may mediate tissue crosstalk.This study aimed to identify specific exercise training-responsive miRNAs that affect skeletal muscle function.Methods miRNA expression profiles of serum-derived EVs were analyzed in healthy young individuals before and after 3 weeks endurance exercise training.Exercise training-responsive miRNAs were then validated for a functional role in cellular metabolic processes in human myotubes.Results We identified several exercise training-responsive miRNAs within exosome-rich EVs in serum,including miR-136-3p.In human myotubes,miR-136-3p enhanced glucose uptake and targeted the nardilysin convertase(NRDC)gene.Transfection of miR-136-3p or silencing of NRDC induced a shift towards glycolytic metabolism in mitochondria and modulated gene expressions related to myogenesis.Pancreatic islets were identified as a potential source of miR-136-3p based on in silico analysis of gene expression and a molecular analysis of conditioned media from isolated pancreatic islets.Conclusion MiR-136-3p is an endurance training-responsive molecular transducer that modulates glucose metabolism and cellular proliferation in myocytes.Associated with EVs,extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk after exercise.Extracellular miR-136-3p may serve as a molecular messenger to communicate islet–skeletal muscle crosstalk.Our results highlight a miRNA-mediated mechanism that participates in inter-organ communication to fine tune the metabolic adaptations to exercise.
文摘Sarcomerogenesis,the addition of serial sarcomeres in skeletal muscle myofibrils and fibres,is a natural occurrence during growth and maturation of animals,including humans.However,the detailed mechanisms that allow for sarcomerogenesis are not fully understood.In some diseases,such as cerebral palsy in children,sarcomerogenesis appears to be inhibited or at least reduced,1,2 often causing severe restrictions in muscle and joint function.
基金Supported by The National Natural Science Foundation of China,No.82103356.
文摘BACKGROUND Improving our understanding of whether increased dietary intake ofω-3 polyunsaturated fatty acids(PUFAs)is beneficial for increasing skeletal muscle mass in patients with metabolic dysfunction-associated fatty liver disease(MAFLD)could provide an important clinical evidence base for the development of relevant nutritional guidelines.AIM To investigate the effect of total dietaryω-3 PUFAs and their subtypes on skeletal muscle mass in MAFLD.METHODS This cross-sectional study involved 2316 participants from four National Health and Nutrition Examination Survey cycles between 2011 and 2018.Dietary intake ofω-3 PUFAs was collected through 24-hour dietary recall interviews.Appendicular skeletal muscle mass index(ASMI)was calculated by dividing ASM in kilograms by height squared.RESULTS The multiple linear regression model showed significant relationships for dietary intake of totalω-3 PUFAs with higher ASMI(β:0.06,95%CI:0.01-0.11)in MAFLD patients.Dietary a-linolenic acid(ALA)(β:0.06,95%CI:0.01-0.12),docosapentaenoic acid(β:1.28,95%CI:0.01-2.54),and docosahexaenoic acid(DHA)(β:0.19,95%CI:0.01-0.37)were significantly associated with higher ASMI,while intake of stearidonic acid and eicosapentaenoic acid did not improve ASMI.In patients with high probability of liver fibrosis,dietary intake of ALA was associated with higher ASMI(β:0.11,95%CI:0.03-0.18).Stratified analysis found that DHA was associated with higher ASMI in patients with obesity and higher metabolic risk.CONCLUSION Increasing dietary intake ofω-3 PUFAs improved skeletal muscle health in patients with MAFLD.Patient with obesity and higher metabolic risk were more likely to benefit from intake of DHA.
基金funded by research grant from National Natural Science Foundation of China(32171135).
文摘Resistance exercise has been confirmed to be important for maintaining muscle mass and function.However,despite considerable experimental studies,the underlying mechanisms still requires further investigation to be elucidated.Sestrin1 is a stress-inducible protein strongly associated with the occurrence and development of skeletal muscle dysfunction.Besides,oxidative stress is believed to be a major pathogenic mechanism in the development of skeletal muscle atrophy,whereas regular exercise training induces the endogenous antioxidative system and protects the body against adverse effects of oxidative stress.Nevertheless,whether Sestrin1 is involved in the amelioration of resistance exercise on muscle atrophy and the role of its antioxidant function in this process remains unknown.Here we show that six-week resistance exercise training significantly improved muscle function,muscle mass,and oxidative damage and maintained the level of Sestrin1 in dexamethasone-treated C57BL/6J mice.Mechanistically,Sestrin1 overexpression rescued protein degradation and oxidative stress in atrophied myotubes.Furthermore,an emerging regulator of cellular defense against toxic and oxidative insults,nuclear factor erythroid2–related factor 2(Nrf2)controls the basal and induced expression of an array of antioxidant response element–dependent genes to regulate the pathophysiological outcomes of oxidant exposure.In this study,we found that Nrf2 is a target of Sestrin1,and Nrf2 nuclear translocation is facilitated by Sestrin1.ML385(an Nrf2 inhibitor)treatment mitigated the regulatory effects of overexpression-Sestrin1.Therefore,Sestrin1 was involved in the process of resistance exercise against skeletal muscle atrophy,which may be closely related to its antioxidant capacity,revealing a potential therapeutic strategy for reducing the loss of skeletal muscle.
文摘Background Heat shock proteins(HSPs)are key molecular chaperones that help maintain protein homeostasis by stabilizing or removing damaged proteins during cellular stress.Aging weakens these stress–response systems,disrupting proteostasis and increasing vulnerability to sarcopenia.High-intensity training(HIT)can counteract these declines by activating protective pathways such as the HSP response.HSPs are highly responsive to stress,examining their regulation during aging is important,as altered HSP activity is linked to the progressive loss of muscle mass.Methods This study investigated the abundance and phosphorylation of HSPs in skeletal muscle from healthy,active young and older adults(n=7 per group),assessed at baseline and again in the older group following 12 weeks of HIT.Using calibrated Western blotting on both whole-muscle homogenates and pooled single muscle fibres,we quantified HSP content and phosphorylation to determine how aging and exercise influence stress–responsive protein regulation at both the tissue and cellular levels.Results In whole muscle homogenates,HSPs(HSP72,HSP27,andαB-crystallin)did not differ between young and older adults,while higher phosphorylation of small HSPs(sHSPs):phospho-HSP27 at Serine15(pHSP27 Ser15)and phospho-αB-crystallin at Serine59(pαB-crystallin Ser59)(∼1.8-fold and∼2.9-fold,respectively)were found in muscle from older adults,indicating higher cellular stress associated with aging.A 12-week HIT intervention in older adults reduced homogenate pHSP27 Ser15 and pαB-crystallin Ser59 abundances to similar levels found in young adults.Total HSPs typically displayed a distinct fiber-type profile in both age groups,with more in type I compared to type II fibers,distinguished by the presence of myosin heavy chain I(MHCI)or MHCII.Phosphorylation at pHSP27 Ser15 and pαB-crystallin Ser59 was not different between type I and type II fibers.The HIT in older adults decreased total and phosphorylated sHSPs in both type I and type II fibers but increased HSP72 in type I fibers.Conclusion HIT has the potential to mitigate age-related cellular stress and modulate protein expression patterns in aging skeletal muscle and,perhaps,has the potential to delay age-related muscle decline,thereby improving muscle health in older adults.
基金financially supported by the Fundamental Research Funds for the Central Universities(JUSRP622014)Collaborative Innovation Center of Food Safety and Quality Control in Jiangsu Province,Jiangnan University(2022-3-2)National Key Research and Development Program of China(2022YFF1100300).
文摘Post-exercise whey protein isolate(WPI)supplement is beneficial for skeletal muscle recovery due to the stimulation of branched chain amino acids(BCAAs).This implies us that intake slow digestion rate of protein to sustain BCAAs releasing rate may facilitate muscle protein synthesis.To examine this hypothesis,we conducted a series of protein supplements including modified slow-digesting whey(SDW),whey,hydrolyzed whey and casein,orally to mice undergoing endurance running.Our results showed that the SDW gavage constant supplied BCAAs in the serum of mice within 6 h and significantly enhanced(P<0.01)endurance exercise capacity,compared to other groups.In addition,the SDW supplementation increased the crosssectional area of mice gastrocnemius fibers,as well as their muscle and liver glycogen content.It also increased the testosterone/cortisol ratio in serum and interleukin-6(IL-6)levels in muscle,while it decreased the tumor necrosis factor-alpha(TNF-α)levels and oxidative stress in muscle.Moreover,it may activate mechanistic target of rapamycin signaling by upregulating mRNA(bcat-1 and pgc-1α)expression.Thus,our findings illustrate that prolonged BCAAs supply duration promotes mice endurance running capacity and skeletal muscle growth,contributing to the advancement of sports nutrition practices.
基金supported by the National Natural Science Foundation of China(No.82172551)the Health Discipline Leader Project of Shanghai Municipal Health Commission(No.2022XD044),China.
文摘Skeletal muscle dysfunction is a common extrapulmonary comorbidity of chronic obstructive pulmonary disease(COPD) and is associated with decreased quality-of-life and survival in patients. The autophagy lysosome pathway is one of the proteolytic systems that significantly affect skeletal muscle structure and function. Intriguingly, both promoting and inhibiting autophagy have been observed to improve COPD skeletal muscle dysfunction, yet the mechanism is unclear. This paper first reviewed the effects of macroautophagy and mitophagy on the structure and function of skeletal muscle in COPD, and then explored the mechanism of autophagy mediating the dysfunction of skeletal muscle in COPD. The results showed that macroautophagy-and mitophagy-related proteins were significantly increased in COPD skeletal muscle. Promoting macroautophagy in COPD improves myogenesis and replication capacity of muscle satellite cells, while inhibiting macroautophagy in COPD myotubes increases their diameters. Mitophagy helps to maintain mitochondrial homeostasis by removing impaired mitochondria in COPD. Autophagy is a promising target for improving COPD skeletal muscle dysfunction, and further research should be conducted to elucidate the specific mechanisms by which autophagy mediates COPD skeletal muscle dysfunction, with the aim of enhancing our understanding in this field.
基金supported by the Swedish Research Council(201500165)a Wallenberg Scholars Award from the Knut and Alice Wallenberg Foundation(KAW 2023.0312)The Novo Nordisk Foundation Center for Basic Metabolic Research is an independent research center at the University of Copenhagen,partially funded by an unrestricted donation from the Novo Nordisk Foundation(NNF23SA0084103).
文摘1.Exercise enhances muscle function and insulin sensitivity Skeletal muscle plays a fundamental role in not only locomotion,but also systemic metabolism.In people with type 2 diabetes,skeletal muscle is a major site of insulin resistance,with impaired insulin signaling and reduced glucose transport activity contributing to metabolic dysfunction.
基金supported by the National Natural Science Foundation of China(32272895 and 32172744).
文摘Background While maternal proline(Pro)supplementation has demonstrated efficacy in enhancing placental angiogenesis and farrowing efficiency in swine,its regulatory role in fetal skeletal muscle ontogeny remains undefined.This study systematically evaluated the temporal-specific impacts of dietary Pro supplementation during critical phases of fetal myogenesis(encompassing primary myofiber formation and secondary myofiber hyperplasia)on offspring muscle development.A total of 120 sows with similar farrowing schedules were assigned to three groups:CON(basal diet),ST-Pro(0.5%Pro supplementation during secondary myofiber formation period,from d 60 gestation to farrowing),LT-Pro(0.5%Pro supplementation spanning primary and secondary myofiber formation period:from d 20 gestation to farrowing).Results LT-Pro group significantly increased the longissimus dorsi(LD)muscle mass per unit body weight in newborn piglets compared to CON group(P<0.05),while no such effect was observed in the ST-Pro group.Metabolomic profiling revealed elevated Pro,lysine,and tryptophan levels in the LD muscle of LT-Pro group piglets,accompanied by reduced branched-chain amino acids(BCAAs;leucine,isoleucine,and valine)in both serum and muscle(P<0.05).Histological analysis demonstrated a 45.74%increase in myofiber cross-sectional area in the LT-Pro group(P<0.05).At the molecular level,LT-Pro group piglets exhibited upregulated mRNA expression levels of myogenic regulatory genes(MYOD1,MYF6)and the cell cycle accelerator CCND1(P<0.05),coupled with activation of the STAT3 signaling pathway(phosphorylated STAT3 protein increased by 2.53-fold,P<0.01).Furthermore,Pro supplementation enhanced oxidative metabolism,evidenced by elevated mitochondrial biogenesis markers(the mRNA expression levels of PPARGC1A,OPA1,and SQSTM1)and a 61.58%increase in succinate dehydrogenase activity(P<0.05).Notably,LT-Pro group piglets showed a selective shift toward slow-twitch oxidative fibers,with both MyHC1 mRNA and protein expression levels significantly upregulated(P<0.05),while the mRNA expression levels of MyHCIIb showed no significant change.Conclusions This study identified the primary fiber formation period as a critical window.Supplementation with Pro during G20–114 reprogrammed offspring skeletal muscle development through STAT3-CCND1-mediated myoblast proliferation,enhanced mitochondrial bioenergetics,and oxidative fiber specification.However,no such effects were observed during G60–114.These findings propose maternal Pro intervention as a novel strategy to enhance muscle yield and metabolic efficiency in swine production,with potential applications for improving meat quality traits linked to oxidative muscle phenotypes.
基金supported by the National Natural Science Foundation of China(No.52475067).
文摘Pneumatic artificial muscles(PAMs)can generate multimodal movements,e.g.,linear contraction/extension,spiral torsion,and bending motions.Among these motions,contraction and extension movements can be achieved using linear PAMs(LPAMs)designed to mimic human skeletal muscle.LPAMs have considerable potential for wearable applications and can be integrated into soft wearable robotic systems.Due to their inherent compliance,excellent human-robot interaction,safety,and low cost,LPAMs are considered potential alternatives as actuator components in the construction of wearable robots.This review presents a comprehensive overview of the bio-inspired design of LPAMs and their wearable applications.The biomechanics of human skeletal muscle,including anatomy,morphology,and biomechanical characterization,is analyzed to provide design inspirations for LPAMs and determine the assistance requirements of LPAM-based wearable robots.Herein,LPAMs are classified into four categories based on their structural shapes,including cylindrical-shaped muscles,flat-shaped muscles,fold-shaped muscles,and muscles with other shapes.In addition,this review provides an overview of the diverse physical interfaces utilized in wearable robots and presents a comparative analysis of the actuation characteristics of LPAMs and the assistance performance of LPAM-based wearable robots.This analysis was conducted in consideration of several key metrics,including the contraction ratio,maximum force,specific force,response frequency,assistive torque/bodyweight,and net metabolic cost.Finally,this review summarizes the ongoing challenges and future research directions.
文摘Metabolic dysfunction-associated steatotic liver disease is increasingly understood to be closely linked with skeletal muscle alterations,such as sarcopenia,myoste-atosis,and metabolic dysregulation,which play a key role in its pathogenesis and progression.Recent literature,including an article by Isakov,highlights the bidirectional interactions between muscle and liver,underscoring shared mechanisms such as insulin resistance,inflammation,and myokine imbalance.This letter reflects on key findings from the review,noting strengths such as its integration of mechanistic insights,discussion of emerging biomarkers,and emphasis on lifestyle and pharmacological interventions.It also identifies areas for further development,including standardization of diagnostic criteria and more rigorous evaluation of translational data.As muscle health gains promi-nence in metabolic dysfunction-associated steatotic liver disease research,multidisciplinary strategies that target both hepatic and muscular systems may offer more effective avenues for prevention and treatment.
文摘Background: Aging-induced cardiac hypertrophy and reduced skeletal muscle strength contribute to increased disease risk and life burden in the elderly. FNDC5 acts as a protective muscle factor in both cardiac and skeletal muscle. This study aims to examine the relationship between cardiac FNDC5 and aging-related cardiac hypertrophy and decreased skeletal muscle strength. Methods: Male young C57BL/6 mice (5 months old, n = 6) and aged mice (21 months old, n = 6) were utilized in the study and housed in a specific pathogen-free (SPF) environment. Prior to the experiment, grip strength tests were performed on the mice, and heart tissues were collected for morphological analysis, including the assessment of peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and fibronectin type III-containing structural domain 5 (FNDC5) protein levels. Furthermore, myosin heavy chain II (MyHC II), skeletal muscle-specific transcription factor (MyoD), muscle RING-finger protein-1 (MuRF1), and FNDC5 levels were evaluated in the quadriceps muscle. The correlations between heart weight and FNDC5 expression levels, as well as skeletal muscle indices in the mice, were subsequently analyzed. Result: Aging leads to cardiac hypertrophy and reduced expression of PGC-1α and FNDC5 proteins. Concurrently, there is a decline in the strength of skeletal muscle, along with decreased expression of MyHC II and increased expression of MURF1 and MyoD. Correlation analysis demonstrated strong positive associations between myocardial FNDC5 protein levels and limb grip strength, as well as MyHC II, and strong negative associations with MyoD and MuRF1. Conclusion: There may be a significant association between aging-induced cardiac hypertrophy and decreased skeletal muscle strength, with FNDC5 potentially playing a crucial role as a regulatory molecule facilitating communication between the heart and skeletal muscle.
文摘BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.
基金supported by the National Natural Science Foundation of China(32071166 and 32072254)the Ministry of Science and Technology of China(2022YFF1100502)+2 种基金the Earmarked Fund for China Agriculture Reasearch System(CARS-08-G19)the“Qing Lan Project”of Jiangsu Province and the Young Elite Scientists Sponsorship Program by CAST(2020QNRC001)Fundamental Research Funds for the Central Universities(JUSRP622027)。
文摘Highland barley tea(HBT)is made from roasted barley seeds and is abundant inβ-glucan,amino acids,minerals,phenolics,and other natural active ingredients.These natural compounds found in whole grains have been shown to slow aging and positively affect skeletal muscle function.As a result,studying the effects of HBT on the skeletal muscle health of the elderly population is critical from a scientific and societal standpoint for improving their health status and reducing the medical burden on society.The antioxidant activity and the content of natural active substances were used as indicators to screen the optimal process of HBT brewing.The effects of long-term HBT consumption on aging in mice were investigated by using HBT as a substitute for drinking water in naturally aging mice for a 5-month intervention.Afterward,various factors were measured,such as basic physiological indices,inflammation,plasma metabolites,skeletal muscle function,and exercise capacity,to evaluate the effects of HBT on aging in mice.Long-term consumption of HBT reduced body and spleen weight,increased body weight percentage of skeletal muscle,and reduced plasma inflammation levels in aging mice.Metabolomic results showed increased plasma levels of the mitochondrial marker short-chain acylcarnitine and some amino acids.Additionally,there was a decrease in bile and long-chain acylcarnitine.The level of fibrosis in the gastrocnemius muscle of aging mice was suppressed,and the percentage of typeⅠmuscle fibers was increased,improving the endurance of the mice.Thus,long-term consumption of HBT may reduce body weight and increase skeletal muscle mitochondrial activity and exercise capacity in aging mice by reducing inflammation levels and alleviating mitochondrial damage.
基金supported by the grants from the National Natural Science Foundation of China(32372873,32441084 and 32172720)the Program for Science&Technology Innovation Talents in Universities of Henan Province,China(22HASTIT038)the Zhongyuan Youth Talent Support Program of China(ZYYCYU202012156).
文摘Skeletal muscle satellite cells are stem cells characterized by their multipotency and capacity for in vitro proliferation.However,primary skeletal muscle satellite cells demonstrate limited proliferative capacity in vitro,which impedes their investigation in poultry skeletal muscle research.Cell immortalization techniques have emerged as valuable tools to address this limitation and facilitate the study of skeletal muscle satellite cell functions.This study achieved the immortalization of chicken skeletal muscle satellite cells through the transduction of primary cells with TERT(telomerase reverse transcriptase)amplified from chicken(chTERT)using a lentiviral vector via telomerase activity reconstitution.While the cells successfully overcame replicative senescence,complete immortalization was not achieved.Initial functional characterization revealed that the proliferative properties and cell cycle characteristics of the immortalized chicken skeletal muscle satellite cell lines(ICMS)closely resembled those of chicken primary muscle satellite cells(CPMSCs).Serum dependency analysis and soft agar assays confirmed that ICMS did not undergo malignant transformation.Furthermore,induced differentiation experiments demonstrated preserved differentiation capacity in ICMS.The established cell lines provide a fundamental framework for developing immortalized poultry cell lines and offer a cellular model for investigating poultry skeletal muscle-related functional genes.
基金Supported by Chongqing Young and Middle-aged Medical High-end Talents,No.YXGD202405Chongqing District and County Head Goose Talents,Chongqing Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.2024ZYYB036Chongqing Banan District Science and Technology and Health Joint Scientific Research Project on Traditional Chinese Medicine,No.BNWJ202300112.
文摘BACKGROUND Many studies have found that sarcopenia is related to the survival of patients with liver cancer,which may lead to worse prognosis.AIM To investigate the relationship between skeletal muscle mass and prognosis in patients with liver cancer receiving targeted therapy by meta-analysis.METHODS PubMed,Embase,Cochrane Library,and Web of Science were searched for clinical studies on the relationship between skeletal muscle index(SMI)and the prognosis of patients with liver cancer receiving targeted therapy from inception to March 1,2022.Meta-analysis and sensitivity analysis of the data were performed using Stata 16.0 software.RESULTS A total of 6877 studies were searched,and finally 12 articles with 1715 cases were included.Meta-analysis result of 8 articles showed that compared with non-low SMI group,the overall survival(OS)of patients with liver cancer in the low SMI group was significantly shorter(hazard ratio=1.60,95%confidence interval:1.44-1.77,P=0.000).Meta-analysis result of 4 articles showed that,compared with low SMI group,patients in the nonlow SMI group had longer OS(hazard ratio=0.59,95%confidence interval:0.38-0.91,P=0.018).CONCLUSION Skeletal muscle mass is positively correlated with OS in patients with liver cancer receiving targeted therapy.
