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1.
Gene ; 768: 145319, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33246031

RESUMO

Myogenesis is a complex, regulated process that involves myoblast proliferation, migration, adhesion, and fusion into myotubes. To investigate early development of embryonic muscles and the expression of regulatory genes during myogenesis in chicken, quail and their hybrids, meat-breeding cocks and egg-breeding cocks were selected as male parents, quails were used as female parents. Their offspring were meat and egg hybrids via Artificial insemination. We measured expression of MUSTN1, IGF-1, and PDK4 using qRT-PCR. We examined muscle fiber diameter using scanning electron microscopy. The results showed that muscle development was two days slower in chicken, egg hybrid, and meat hybrid than in quail. Muscle fiber spacing was the largest in chicken, followed by meat hybrid, egg hybrid, and quail. A similar trend was obtained for muscle fiber diameter. Additionally, muscle fiber diameter increased with embryogenesis. The sarcomere was present on day 17 of incubation in quail, but not in the other species. MUSTN1 could up-regulated IGF-1 by activating PI3K/Akt. IGF-1 expression was consistent with myoblast proliferation and myotube fusion. PDK4 was expressed from E7 to E17. The first peak was reached on E10, egg hybrid and meat hybrid reached their peak at E15. PDK4 is involved in the early proliferation and differentiation of muscle, thereby affecting muscle growth and development. Our findings demonstrated that MUSTN1, IGF-1 and PDK4 genes are expressed to varying levels in breast muscle of chicken, quail, egg hybrid and meat hybrid during the embryonic period. Interestingly, with increasing embryonic age, muscle development was approximately 48 h faster in quail than in other species. We speculated that MUSTN1, IGF-1 and PDK4 genes may be the main candidate genes that cause differences in poultry muscle traits, but the molecular regulation mechanisms need to be further studied. Our findings shed some light on the avian embryo muscle formation and molecular breeding of poultry muscle traits, which provide theoretical basis for poultry breeding.


Assuntos
Quimera/embriologia , Fator de Crescimento Insulin-Like I/genética , Músculo Esquelético/crescimento & desenvolvimento , Proteínas Nucleares/genética , /genética , Animais , Cruzamento , Galinhas , Quimera/genética , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Masculino , Microscopia de Força Atômica , Desenvolvimento Muscular , Músculo Esquelético/metabolismo , Codorniz
2.
Nat Commun ; 11(1): 6287, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293533

RESUMO

Mammalian cells exhibit remarkable diversity in cell size, but the factors that regulate establishment and maintenance of these sizes remain poorly understood. This is especially true for skeletal muscle, comprised of syncytial myofibers that each accrue hundreds of nuclei during development. Here, we directly explore the assumed causal relationship between multinucleation and establishment of normal size through titration of myonuclear numbers during mouse neonatal development. Three independent mouse models, where myonuclear numbers were reduced by 75, 55, or 25%, led to the discovery that myonuclei possess a reserve capacity to support larger functional cytoplasmic volumes in developing myofibers. Surprisingly, the results revealed an inverse relationship between nuclei numbers and reserve capacity. We propose that as myonuclear numbers increase, the range of transcriptional return on a per nuclear basis in myofibers diminishes, which accounts for both the absolute reliance developing myofibers have on nuclear accrual to establish size, and the limits of adaptability in adult skeletal muscle.


Assuntos
Núcleo Celular , Tamanho Celular , Músculo Esquelético/crescimento & desenvolvimento , Células Satélites de Músculo Esquelético/citologia , Animais , Feminino , Masculino , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Transgênicos , Modelos Animais , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/metabolismo
3.
Nat Commun ; 11(1): 6288, 2020 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-33293572

RESUMO

Muscle fibers are the largest cells in the body, and one of its few syncytia. Individual cell sizes are variable and adaptable, but what governs cell size has been unclear. We find that muscle fibers are DNA scarce compared to other cells, and that the nuclear number (N) adheres to the relationship N = aVb where V is the cytoplasmic volume. N invariably scales sublinearly to V (b < 1), making larger cells even more DNA scarce. N scales linearly to cell surface in adult humans, in adult and developing mice, and in mice with genetically reduced N, but in the latter the relationship eventually fails when they reach adulthood with extremely large myonuclear domains. Another exception is denervation-atrophy where nuclei are not eliminated. In conclusion, scaling exponents are remarkably similar across species, developmental stages and experimental conditions, suggesting an underlying scaling law where DNA-content functions as a limiter of muscle cell size.


Assuntos
Núcleo Celular/química , Tamanho Celular , DNA/análise , Fibras Musculares Esqueléticas/citologia , Músculo Esquelético/crescimento & desenvolvimento , Adulto , Animais , Biópsia , Citoplasma , Feminino , Voluntários Saudáveis , Humanos , Microscopia Intravital , Masculino , Camundongos , Microscopia Confocal , Fibras Musculares Esqueléticas/química , Músculo Esquelético/citologia , Músculo Esquelético/patologia , Análise de Célula Única , Adulto Jovem
4.
Nat Commun ; 11(1): 6375, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311457

RESUMO

Syncytial skeletal muscle cells contain hundreds of nuclei in a shared cytoplasm. We investigated nuclear heterogeneity and transcriptional dynamics in the uninjured and regenerating muscle using single-nucleus RNA-sequencing (snRNAseq) of isolated nuclei from muscle fibers. This revealed distinct nuclear subtypes unrelated to fiber type diversity, previously unknown subtypes as well as the expected ones at the neuromuscular and myotendinous junctions. In fibers of the Mdx dystrophy mouse model, distinct subtypes emerged, among them nuclei expressing a repair signature that were also abundant in the muscle of dystrophy patients, and a nuclear population associated with necrotic fibers. Finally, modifications of our approach revealed the compartmentalization in the rare and specialized muscle spindle. Our data identifies nuclear compartments of the myofiber and defines a molecular roadmap for their functional analyses; the data can be freely explored on the MyoExplorer server ( https://shiny.mdc-berlin.de/MyoExplorer/ ).


Assuntos
Núcleo Celular/genética , Núcleo Celular/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Transcriptoma , Animais , Linhagem Celular , Citoplasma , Modelos Animais de Doenças , Regulação da Expressão Gênica no Desenvolvimento , Heterogeneidade Genética , Humanos , Camundongos , Camundongos Endogâmicos mdx , Fibras Musculares Esqueléticas , Músculo Esquelético/citologia , Distrofias Musculares/genética , Distrofias Musculares/metabolismo , RNA-Seq , Regeneração , Tendões
5.
Nat Commun ; 11(1): 6374, 2020 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-33311464

RESUMO

While the majority of cells contain a single nucleus, cell types such as trophoblasts, osteoclasts, and skeletal myofibers require multinucleation. One advantage of multinucleation can be the assignment of distinct functions to different nuclei, but comprehensive interrogation of transcriptional heterogeneity within multinucleated tissues has been challenging due to the presence of a shared cytoplasm. Here, we utilized single-nucleus RNA-sequencing (snRNA-seq) to determine the extent of transcriptional diversity within multinucleated skeletal myofibers. Nuclei from mouse skeletal muscle were profiled across the lifespan, which revealed the presence of distinct myonuclear populations emerging in postnatal development as well as aging muscle. Our datasets also provided a platform for discovery of genes associated with rare specialized regions of the muscle cell, including markers of the myotendinous junction and functionally validated factors expressed at the neuromuscular junction. These findings reveal that myonuclei within syncytial muscle fibers possess distinct transcriptional profiles that regulate muscle biology.


Assuntos
Núcleo Celular/genética , Heterogeneidade Genética , Fibras Musculares Esqueléticas/metabolismo , RNA-Seq/métodos , Animais , Núcleo Celular/metabolismo , Citoplasma , Genômica , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Junção Neuromuscular , Análise de Sequência de RNA , Tendões
6.
Nat Commun ; 11(1): 5808, 2020 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-33199701

RESUMO

Skeletal muscle promotes metabolic balance by regulating glucose uptake and the stimulation of multiple interorgan crosstalk. We show here that the catalytic activity of Vav2, a Rho GTPase activator, modulates the signaling output of the IGF1- and insulin-stimulated phosphatidylinositol 3-kinase pathway in that tissue. Consistent with this, mice bearing a Vav2 protein with decreased catalytic activity exhibit reduced muscle mass, lack of proper insulin responsiveness and, at much later times, a metabolic syndrome-like condition. Conversely, mice expressing a catalytically hyperactive Vav2 develop muscle hypertrophy and increased insulin responsiveness. Of note, while hypoactive Vav2 predisposes to, hyperactive Vav2 protects against high fat diet-induced metabolic imbalance. These data unveil a regulatory layer affecting the signaling output of insulin family factors in muscle.


Assuntos
Biocatálise , Homeostase , Metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Proteínas Proto-Oncogênicas c-vav/metabolismo , Transdução de Sinais , Adipócitos Brancos/efeitos dos fármacos , Adipócitos Brancos/metabolismo , Tecido Adiposo Marrom/metabolismo , Animais , Biocatálise/efeitos dos fármacos , Composição Corporal/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Linhagem Celular , Tamanho Celular/efeitos dos fármacos , Genótipo , Glucose/farmacologia , Homeostase/efeitos dos fármacos , Insulina/metabolismo , Fator de Crescimento Insulin-Like I/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Musculares/citologia , Células Musculares/efeitos dos fármacos , Células Musculares/metabolismo , Músculo Esquelético/efeitos dos fármacos , Tamanho do Órgão/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Proteínas rac1 de Ligação ao GTP/metabolismo
7.
Nat Commun ; 11(1): 5102, 2020 10 09.
Artigo em Inglês | MEDLINE | ID: mdl-33037211

RESUMO

Skeletal muscle fibers are large syncytia but it is currently unknown whether gene expression is coordinately regulated in their numerous nuclei. Here we show by snRNA-seq and snATAC-seq that slow, fast, myotendinous and neuromuscular junction myonuclei each have different transcriptional programs, associated with distinct chromatin states and combinations of transcription factors. In adult mice, identified myofiber types predominantly express either a slow or one of the three fast isoforms of Myosin heavy chain (MYH) proteins, while a small number of hybrid fibers can express more than one MYH. By snRNA-seq and FISH, we show that the majority of myonuclei within a myofiber are synchronized, coordinately expressing only one fast Myh isoform with a preferential panel of muscle-specific genes. Importantly, this coordination of expression occurs early during post-natal development and depends on innervation. These findings highlight a previously undefined mechanism of coordination of gene expression in a syncytium.


Assuntos
Núcleo Celular/genética , Regulação da Expressão Gênica , Hibridização in Situ Fluorescente/métodos , Fibras Musculares Esqueléticas/citologia , Fibras Musculares Esqueléticas/fisiologia , Análise de Sequência de RNA/métodos , Animais , Feminino , Camundongos Endogâmicos C57BL , Músculo Esquelético/citologia , Músculo Esquelético/embriologia , Músculo Esquelético/crescimento & desenvolvimento , Cadeias Pesadas de Miosina/genética , Junção Neuromuscular/citologia , Análise de Célula Única , Tendões/citologia , Transcrição Genética
8.
Nat Commun ; 11(1): 4356, 2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32868777

RESUMO

Complex motor commands for human locomotion are generated through the combination of motor modules representable as muscle synergies. Recent data have argued that muscle synergies are inborn or determined early in life, but development of the neuro-musculoskeletal system and acquisition of new skills may demand fine-tuning or reshaping of the early synergies. We seek to understand how locomotor synergies change during development and training by studying the synergies for running in preschoolers and diverse adults from sedentary subjects to elite marathoners, totaling 63 subjects assessed over 100 sessions. During development, synergies are fractionated into units with fewer muscles. As adults train to run, specific synergies coalesce to become merged synergies. Presences of specific synergy-merging patterns correlate with enhanced or reduced running efficiency. Fractionation and merging of muscle synergies may be a mechanism for modifying early motor modules (Nature) to accommodate the changing limb biomechanics and influences from sensorimotor training (Nurture).


Assuntos
Músculo Esquelético/fisiologia , Corrida/fisiologia , Adulto , Fenômenos Biomecânicos , Criança , Pré-Escolar , Eletromiografia , Feminino , Humanos , Locomoção , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/crescimento & desenvolvimento
9.
J Anim Sci ; 98(8)2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32745187

RESUMO

Proof-of-principle for large-scale engineering of edible muscle tissue, in vitro, was established with the product's introduction in 2013. Subsequent research and commentary on the potential for cell-based meat to be a viable food option and potential alternative to conventional meat have been significant. While some of this has focused on the biology and engineering required to optimize the manufacturing process, a majority of debate has focused on cultural, environmental, and regulatory considerations. Animal scientists and others with expertise in muscle and cell biology, physiology, and meat science have contributed to the knowledge base that has made cell-based meat possible and will continue to have a role in the future of the new product. Importantly, the successful introduction of cell-based meat that looks and tastes like conventional meat at a comparable price has the potential to displace and/or complement conventional meat in the marketplace.


Assuntos
Comportamento do Consumidor , Tecnologia de Alimentos , Carne/provisão & distribução , Animais , Cultura , Preferências Alimentares , Humanos , Músculo Esquelético/crescimento & desenvolvimento , Células-Tronco , Técnicas de Cultura de Tecidos , Estados Unidos , United States Food and Drug Administration
10.
J Neurosci ; 40(38): 7203-7215, 2020 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-32817327

RESUMO

During aging, skeletal muscles become atrophic and lose contractile force. Aging can also impact the neuromuscular junction (NMJ), a synapse that transmits signals from motoneurons to muscle fibers to control muscle contraction. However, in contrast to muscle aging that has been studied extensively, less is known about the molecular mechanisms of NMJ aging although its structure and function are impaired in aged animals. To this end, we performed RNA sequencing (RNA-seq) analysis to identify genes whose expression in synapse-rich region is altered. Gene ontology (GO) analysis highlighted genes relating to nuclear structure or function. In particular, lamin A/C, an intermediate filament protein critical for the interphase nuclear architecture, was reduced. Remarkably, mutation of lamin A/C in muscles or motoneurons had no effect on NMJ formation in either sex of mice, but the muscle mutation caused progressive denervation, acetylcholine receptor (AChR) cluster fragmentation, and neuromuscular dysfunction. Interestingly, rapsyn, a protein critical to AChR clustering, was reduced in mutant muscle cells; and expressing rapsyn in muscles attenuated NMJ deficits of HSA-Lmna-/- mice. These results reveal a role of lamin A/C in NMJ maintenance and suggest that nuclear dysfunction or deficiency may contribute to NMJ deficits in aged muscles.SIGNIFICANCE STATEMENT This study provides evidence that lamin A/C, a scaffolding component of the nuclear envelope, is critical to maintaining the NMJ in mice. Its muscle-specific mutation led to progressive NMJ degeneration in vivo We showed that the mutation reduced the level of rapsyn, a protein necessary for acetylcholine receptor (AChR) clustering; and expression of rapsyn in muscles attenuated NMJ deficits of HSA-Lmna-/- mice. These results reveal a role of lamin A/C in NMJ maintenance and suggest that nuclear dysfunction or deficiency may contribute to NMJ deficits in aged muscles.


Assuntos
Envelhecimento/metabolismo , Lamina Tipo A/metabolismo , Junção Neuromuscular/metabolismo , Envelhecimento/genética , Envelhecimento/patologia , Animais , Antígeno CD24/genética , Antígeno CD24/metabolismo , Feminino , Lamina Tipo A/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Musculares/genética , Proteínas Musculares/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Músculo Esquelético/patologia , Mutação , Junção Neuromuscular/patologia , Receptores Colinérgicos/metabolismo
11.
Exerc Sport Sci Rev ; 48(4): 180-187, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32658044

RESUMO

Low-load blood flow restricted resistance exercise (BFRRE) can stimulate whole-muscle growth and improve muscle function. However, limited knowledge exists on the effects at the myocellular level. We hypothesize that BFRRE has the ability to produce concurrent skeletal muscle myofibrillar, mitochondrial, and microvascular adaptations, thus offering an alternative strategy to counteract decay in skeletal muscle health and function in clinical populations.


Assuntos
Adaptação Fisiológica , Microcirculação/fisiologia , Mitocôndrias Musculares/metabolismo , Músculo Esquelético/irrigação sanguínea , Miofibrilas/fisiologia , Treinamento de Resistência/métodos , Humanos , Proteínas Musculares/biossíntese , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/fisiologia , Consumo de Oxigênio , Fluxo Sanguíneo Regional
12.
PLoS One ; 15(6): e0234552, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32525949

RESUMO

INTRODUCTION: Digital tools like 3D laser-based photonic scanners, which can assess external anthropometric measurements for population based studies, and predict body composition, are gaining in importance. Here we focus on a) systematic deviation between manually determined and scanned standard measurements, b) differences regarding the strength of association between these standard measurements and body composition, and c) improving these predictions of body composition by considering additional scan measurements. METHODS: We analysed 104 men aged 19-23. Bioelectrical Impedance Analysis was used to estimate whole body fat mass, visceral fat mass and skeletal muscle mass (SMM). For the 3D body scans, an Anthroscan VITUSbodyscan was used to automatically obtain 90 body shape measurements. Manual anthropometric measurements (height, weight, waist circumference) were also taken. RESULTS: Scanned and manually measured height, waist circumference, waist-to-height-ratio, and BMI were strongly correlated (Spearman Rho>0.96), however we also found systematic differences. When these variables were used to predict body fat or muscle mass, explained variation and prediction standard errors were similar between scanned and manual measurements. The univariable predictions performed well for both visceral fat (r2 up to 0.92) and absolute fat mass (AFM, r2 up to 0.87) but not for SMM (r2 up to 0.54). Of the 90 body scanner measures used in the multivariable prediction models, belly circumference and middle hip circumference were the most important predictors of body fat content. Stepwise forward model selection using the AIC criterion showed that the best predictive power (r2 up to 0.99) was achieved with models including 49 scanner measurements. CONCLUSION: The use of a 3D full body scanner produced results that strongly correlate to manually measured anthropometric measures. Predictions were improved substantially by including multiple measurements, which can only be obtained with a 3D body scanner, in the models.


Assuntos
Adiposidade , Imageamento Tridimensional/normas , Músculo Esquelético/diagnóstico por imagem , Imagem Óptica/normas , Gordura Abdominal/diagnóstico por imagem , Gordura Abdominal/crescimento & desenvolvimento , Tamanho Corporal , Impedância Elétrica , Humanos , Masculino , Militares/estatística & dados numéricos , Músculo Esquelético/crescimento & desenvolvimento , Reprodutibilidade dos Testes , Suíça , Adulto Jovem
13.
J Neurosci ; 40(35): 6722-6731, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32487696

RESUMO

Progressive changes in vocal behavior over the course of vocal imitation leaning are often attributed exclusively to developing neural circuits, but the effects of postnatal body changes remain unknown. In songbirds, the syrinx transforms song system motor commands into sound and exhibits changes during song learning. Here we test the hypothesis that the transformation from motor commands to force trajectories by syringeal muscles functionally changes over vocal development in zebra finches. Our data collected in both sexes show that, only in males, muscle speed significantly increases and that supralinear summation occurs and increases with muscle contraction speed. Furthermore, we show that previously reported submillisecond spike timing in the avian cortex can be resolved by superfast syringeal muscles and that the sensitivity to spike timing increases with speed. Because motor neuron and muscle properties are tightly linked, we make predictions on the boundaries of the yet unknown motor code that correspond well with cortical activity. Together, we show that syringeal muscles undergo essential transformations during song learning that drastically change how neural commands are translated into force profiles and thereby acoustic features. We propose that the song system motor code must compensate for these changes to achieve its acoustic targets. Our data thus support the hypothesis that the neuromuscular transformation changes over vocal development and emphasizes the need for an embodied view of song motor learning.SIGNIFICANCE STATEMENT Fine motor skill learning typically occurs in a postnatal period when the brain is learning to control a body that is changing dramatically due to growth and development. How the developing body influences motor code formation and vice versa remains largely unknown. Here we show that vocal muscles in songbirds undergo critical transformations during song learning that drastically change how neural commands are translated into force profiles and thereby acoustic features. We propose that the motor code must compensate for these changes to achieve its acoustic targets. Our data thus support the hypothesis that the neuromuscular transformation changes over vocal development and emphasizes the need for an embodied view of song motor learning.


Assuntos
Contração Muscular , Músculo Esquelético/crescimento & desenvolvimento , Junção Neuromuscular/fisiologia , Vocalização Animal , Animais , Feminino , Tentilhões , Aprendizagem , Masculino , Neurônios Motores/fisiologia , Músculo Esquelético/inervação , Músculo Esquelético/fisiologia , Potenciais Sinápticos
14.
PLoS Genet ; 16(5): e1008586, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32463816

RESUMO

The strength of bone depends on bone quantity and quality. Osteocalcin (Ocn) is the most abundant noncollagenous protein in bone and is produced by osteoblasts. It has been previously claimed that Ocn inhibits bone formation and also functions as a hormone to regulate insulin secretion in the pancreas, testosterone synthesis in the testes, and muscle mass. We generated Ocn-deficient (Ocn-/-) mice by deleting Bglap and Bglap2. Analysis of Ocn-/-mice revealed that Ocn is not involved in the regulation of bone quantity, glucose metabolism, testosterone synthesis, or muscle mass. The orientation degree of collagen fibrils and size of biological apatite (BAp) crystallites in the c-axis were normal in the Ocn-/-bone. However, the crystallographic orientation of the BAp c-axis, which is normally parallel to collagen fibrils, was severely disrupted, resulting in reduced bone strength. These results demonstrate that Ocn is required for bone quality and strength by adjusting the alignment of BAp crystallites parallel to collagen fibrils; but it does not function as a hormone.


Assuntos
Apatitas/metabolismo , Calcificação Fisiológica/genética , Metabolismo dos Carboidratos/genética , Glucose/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Osteocalcina/fisiologia , Testosterona/biossíntese , Animais , Apatitas/química , Osso e Ossos/metabolismo , Colágeno/metabolismo , Cristalização , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Desenvolvimento Muscular/genética , Músculo Esquelético/metabolismo , Tamanho do Órgão/genética , Osteoblastos/metabolismo , Osteocalcina/genética , Osteogênese/genética , Testículo/crescimento & desenvolvimento , Testículo/metabolismo
15.
Am J Physiol Regul Integr Comp Physiol ; 319(1): R50-R58, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32432913

RESUMO

The current study explored whether the marked hypertrophic response noted with a short-term unilateral concurrent exercise paradigm was associated with more prominent changes in myonuclei accretion, ribosome biogenesis, and capillarization compared with resistance exercise alone (RE). Ten men (age 25 ± 4 yr) performed aerobic and resistance exercise (AE + RE) for one leg while the other leg did RE. Muscle biopsies were obtained before and after 5 wk of training and subjected to fiber-type specific immunohistochemical analysis, and quantification of total RNA content and mRNA/rRNA transcript abundance. Type II fiber cross-sectional area (CSA) increased with both AE + RE (22%) and RE (16%), while type I fiber CSA increased mainly with AE + RE (16%). The change score tended to differ between legs for type I CSA (P = 0.099), and the increase in smallest fiber diameter was greater in AE + RE than RE (P = 0.029). The number of nuclei per fiber increased after AE + RE in both fiber types, and this increase was greater (P = 0.027) than after RE. A strong correlation was observed between changes in number of nuclei per fiber and fiber CSA in both fiber types, for both AE + RE and RE (r > 0.8, P < 0.004). RNA content increased after AE + RE (24%, P = 0.019), but the change-scores did not differ across legs. The capillary variables generally increased in both fiber types, with no difference across legs. In conclusion, the accentuated hypertrophic response to AE + RE was associated with more pronounced myonuclear accretion, which was strongly correlated with the degree of fiber hypertrophy. This suggests that myonuclear accretion could play a role in facilitating muscle hypertrophy also during very short training periods.


Assuntos
Núcleo Celular/metabolismo , Exercício Físico/fisiologia , Músculo Esquelético/fisiologia , Adulto , Capilares/fisiologia , Humanos , Hipertrofia , Perna (Membro)/anatomia & histologia , Perna (Membro)/fisiologia , Imagem por Ressonância Magnética , Masculino , Fibras Musculares de Contração Rápida/fisiologia , Fibras Musculares de Contração Rápida/ultraestrutura , Fibras Musculares de Contração Lenta/fisiologia , Fibras Musculares de Contração Lenta/ultraestrutura , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/ultraestrutura , Resistência Física , RNA/biossíntese , Treinamento de Resistência , Ribossomos/metabolismo , Adulto Jovem
16.
BMC Genomics ; 21(1): 327, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32349667

RESUMO

BACKGROUND: DNA methylation is an epigenetic regulatory form that plays an important role in regulating the gene expression and the tissues development.. However, DNA methylation regulators involved in sheep muscle development remain unclear. To explore the functional importance of genome-scale DNA methylation during sheep muscle growth, this study systematically investigated the genome-wide DNA methylation profiles at key stages of Hu sheep developmental (fetus and adult) using deep whole-genome bisulfite sequencing (WGBS). RESULTS: Our study found that the expression levels of DNA methyltransferase (DNMT)-related genes were lower in fetal muscle than in the muscle of adults. The methylation levels in the CG context were higher than those in the CHG and CHH contexts, and methylation levels were highest in introns, followed by exons and downstream regions. Subsequently, we identified 48,491, 17, and 135 differentially methylated regions (DMRs) in the CG, CHG, and CHH sequence contexts and 11,522 differentially methylated genes (DMGs). The results of bisulfite sequencing PCR (BSP) correlated well with the WGBS-Seq data. Moreover, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) functional annotation analysis revealed that some DMGs were involved in regulating skeletal muscle development and fatty acid metabolism. By combining the WGBS-Seq and previous RNA-Seq data, a total of 159 overlap genes were obtained between differentially expressed genes (DEGs) and DMGs (FPKM > 10 and fold change > 4). Finally, we found that 9 DMGs were likely to be involved in muscle growth and metabolism of Hu sheep. CONCLUSIONS: We systemically studied the global DNA methylation patterns of fetal and adult muscle development in Hu sheep, which provided new insights into a better understanding of the epigenetic regulation of sheep muscle development.


Assuntos
Metilação de DNA , Epigenoma , Desenvolvimento Muscular/genética , Músculo Esquelético/crescimento & desenvolvimento , Animais , DNA (Citosina-5-)-Metiltransferases/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , Epigênese Genética , Regulação da Expressão Gênica no Desenvolvimento , Redes Reguladoras de Genes , Músculo Esquelético/embriologia , Músculo Esquelético/metabolismo , Análise de Sequência de DNA , Ovinos , Sulfitos/química
17.
Int J Mol Sci ; 21(7)2020 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-32260521

RESUMO

Skeletal muscle differentiation is triggered by a unique family of myogenic basic helix-loop-helix transcription factors, including MyoD, MRF-4, Myf-5, and Myogenin. These transcription factors bind promoters and distant regulatory regions, including E-box elements, of genes whose expression is restricted to muscle cells. Other E-box binding zinc finger proteins target the same DNA response elements, however, their function in muscle development and regeneration is still unknown. Here, we show that the transcription factor zinc finger E-box-binding homeobox 2 (Zeb2, Sip-1, Zfhx1b) is present in skeletal muscle tissues. We investigate the role of Zeb2 in skeletal muscle differentiation using genetic tools and transgenic mouse embryonic stem cells, together with single-cell RNA-sequencing and in vivo muscle engraftment capability. We show that Zeb2 over-expression has a positive impact on skeletal muscle differentiation in pluripotent stem cells and adult myogenic progenitors. We therefore propose that Zeb2 is a novel myogenic regulator and a possible target for improving skeletal muscle regeneration. The non-neural roles of Zeb2 are poorly understood.


Assuntos
Diferenciação Celular , Desenvolvimento Muscular , Células-Tronco Pluripotentes/metabolismo , Homeobox 2 de Ligação a E-box com Dedos de Zinco/metabolismo , Animais , Linhagem Celular , Masculino , Camundongos , Camundongos Nus , Músculo Esquelético/citologia , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Mioblastos/citologia , Mioblastos/metabolismo , Células-Tronco Pluripotentes/citologia , Homeobox 2 de Ligação a E-box com Dedos de Zinco/genética
18.
J Nutr ; 150(7): 1845-1851, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32321161

RESUMO

BACKGROUND: Although daily protein intake (PI) has been reported to be essential for regulating muscle mass, the distribution of daily PI in individuals is typically the lowest at breakfast and skewed toward dinner. Skewed protein intake patterns and inadequate PI at breakfast were reported to be negative factors for muscle maintenance. OBJECTIVES: This study examined whether a protein-enriched meal at breakfast is more effective for muscle accretion compared with the typical skewed PI pattern. METHODS: This 12-wk, parallel-group, randomized clinical trial included 26 men (means ± SEs; age: 20.8 ± 0.4 y; BMI: 21.8 ± 0.4 kg/m2). The "high breakfast" (HBR) group (n = 12) consumed a protein-enriched meal at breakfast providing a PI of 0.33 g/kg body weight (BW); their PI at lunch (0.46 g/kg BW) and dinner (0.48 g/kg BW) provided an adequate overall daily PI (1.30 g/kg BW/d). The "low breakfast" (LBR) group (n = 14) consumed 0.12 g protein/kg BW at breakfast; intakes at lunch (0.45 g/kg BW) and dinner (0.83 g/kg BW) yielded the same daily PI as in the HBR group. The participants performed supervised resistance training (RT) 3 times per week (75-80% 1-repetition maximum; 3 sets × 10 repetitions). DXA was used to measure the primary outcome variable, that is, total lean soft tissue mass (LTM). RESULTS: The total LTM at baseline did not differ between the HBR (52.4 ± 1.3 kg) and LBR (53.4 ± 1.2 kg) groups. After the intervention, increases in total LTM were significant in both groups, with that in the HBR group (2.5 ± 0.3 kg) tending to be greater than that in the LBR group (1.8 ± 0.3 kg) (P = 0.06), with a large effect size (Cohen d = 0.795). CONCLUSIONS: For RT-induced muscle hypertrophy in healthy young men, consuming a protein-enriched meal at breakfast and less protein at dinner while achieving an adequate overall PI is more effective than consuming more protein at dinner.This study was registered at University hospital Medical Information Network (UMIN) Clinical Trials Registry as UMIN000037583 (https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000042763).


Assuntos
Proteínas na Dieta/administração & dosagem , Refeições , Músculo Esquelético/crescimento & desenvolvimento , Treinamento de Resistência , Adolescente , Adulto , Humanos , Masculino , Adulto Jovem
19.
Sci Rep ; 10(1): 6149, 2020 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-32273524

RESUMO

Low birth weight (LBW) can cause lifelong impairments in muscle development and growth. Satellite cells (SC) and their progeny are crucial contributors to myogenic processes. This study provides new data on LBW in piglets combining insights on energy metabolism, muscle capillarization and differences in SC presence and function. To this aim, muscle tissues as well as isolated myogenic cells of 4-day-old German Landrace piglets were analyzed. For the first time two heterogeneous SC subpopulations, which contribute differently to muscle development, were isolated from LBW pigs by Percoll density gradient centrifugation. The muscles of LBW piglets showed a reduced DNA, RNA, and protein content as well as lower activity of the muscle specific enzymes CK, ICDH, and LDH compared to their normal birth weight siblings. We assume that deficits in energy metabolism and capillarization are associated with reduced bioavailability of SC, possibly leading to early exhaustion of the SC reserve cell pool and the cells' premature differentiation.


Assuntos
Peso ao Nascer , Células Satélites de Músculo Esquelético/fisiologia , Animais , Animais Recém-Nascidos/crescimento & desenvolvimento , Animais Recém-Nascidos/metabolismo , Animais Recém-Nascidos/fisiologia , Peso ao Nascer/fisiologia , Centrifugação com Gradiente de Concentração , Creatina Quinase/metabolismo , Metabolismo Energético , Feminino , Isocitrato Desidrogenase/metabolismo , L-Lactato Desidrogenase/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Músculo Esquelético/metabolismo , Células Satélites de Músculo Esquelético/metabolismo , Suínos/crescimento & desenvolvimento , Suínos/metabolismo
20.
J Agric Food Chem ; 68(17): 4884-4892, 2020 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-32275833

RESUMO

Skeletal muscle is the primary source of protein for humans. However, the mechanisms of skeletal muscle growth, such as nutrition control, remain unknown. Moreover, the function of lysine (Lys) in controling skeletal muscle growth has gradually demonstrated that Lys is not only substantial for protein synthesis but also a signaling molecule for satellite cell (SC) activation. In the current work, the number of differentiated SCs in the longissimus thoracis muscle and the fusion index of SCs were both governed by Lys supplementation. Meanwhile, the myogenic regulatory factors and the mammalian target of rapamycin complex 1 (mTORC1) pathway showed the same tendencies of changes as the differentiation of SCs. After Lys was resupplemented with rapamycin, the mTORC1 pathway was inhibited and the differentiation ability of SCs was suppressed. Collectively, the results showed that the mTORC1-pathway-mediated SC differentiation was required for Lys-promoted skeletal muscle growth.


Assuntos
Lisina/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Músculo Esquelético/crescimento & desenvolvimento , Células Satélites de Músculo Esquelético/citologia , Células Satélites de Músculo Esquelético/metabolismo , Animais , Diferenciação Celular , Alvo Mecanístico do Complexo 1 de Rapamicina/genética , Músculo Esquelético/metabolismo , Suínos
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