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1.
Mol Biol Rep ; 51(1): 884, 2024 Aug 02.
Article de Anglais | MEDLINE | ID: mdl-39093510

RÉSUMÉ

BACKGROUND: Brown adipose tissue (BAT) is a thermogenic tissue that uncouples oxidative phosphorylation from ATP synthesis and increases energy expenditure via non-shivering thermogenesis in mammals. Cold exposure and exercise have been shown to increase BAT and browning of white adipose tissue (WAT) in mice. This study aimed to determine whether there is an additive effect of exercise during cold exposure on markers related to browning of adipose tissue. in Wistar rats. METHODS: Twenty-four male Wistar rats were randomly divided into three groups: Control (C, 25˚C), Swimming in Neutral (SN, 30˚C) water, and Swimming in Cold (SC, 15˚C) water. Swimming included intervals of 2-3 min, 1 min rest, until exhausted, three days a week for six weeks, with a training load of 3-6% body weight. After the experimental protocol, interscapular BAT and inguinal subcutaneous white adipose tissue (WAT) were excised, weighed, and processed for beiging marker gene expression. RESULTS: SN and SC resulted in lower body weight gain, associated with reduced WAT and BAT volume and increased BAT number with greater effects observed in SC. Myostatin protein expression was lower in BAT, WAT, soleus muscle, and serum NC and SC compared to the C group. Expression of the interferon regulatory factor-4 (IRF4) gene in both BAT and WAT tissues was significantly greater in the SC than in the C. Expression of the PGC-1α in BAT was significantly increased in the SC compared to C and increased in WAT in NC and SC. Expression of the UCP1 in BAT and WAT increased in the SC group compared to other groups. CONCLUSION: The findings demonstrate that six weeks of swimming training in cold water promotes additive effects of the expression of genes and proteins involved in the browning process of adipose tissue in Wistar rats. Myostatin inhibition may possess a regulator effect on the PGC-1α - UCP1 pathway that mediates adipose tissue browning.


Sujet(s)
Tissu adipeux brun , Tissu adipeux blanc , Basse température , Myostatine , Conditionnement physique d'animal , Rat Wistar , Natation , Thermogenèse , Animaux , Tissu adipeux brun/métabolisme , Myostatine/métabolisme , Myostatine/génétique , Natation/physiologie , Mâle , Rats , Tissu adipeux blanc/métabolisme , Thermogenèse/physiologie , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes/métabolisme , Coactivateur 1-alpha du récepteur gamma activé par les proliférateurs de peroxysomes/génétique , Métabolisme énergétique , Transduction du signal , Eau/métabolisme , Poids
2.
PLoS One ; 19(7): e0299975, 2024.
Article de Anglais | MEDLINE | ID: mdl-38959242

RÉSUMÉ

Skeletal muscle growth is an economically important trait in the cattle industry. Secreted muscle-derived proteins, referred to as myokines, have important roles in regulating the growth, metabolism, and health of skeletal muscle in human and biomedical research models. Accumulating evidence supports the importance of myokines in skeletal muscle and whole-body health, though little is known about the potential presence and functional significance of these proteins in cattle. This study evaluates and confirms that secreted proteins acidic and rich in cysteine (SPARC), fibroblast growth factor 21 (FGF-21), myostatin (MSTN), and decorin (DCN) are expressed and SPARC, FGF-21, and DCN are secreted by primary bovine satellite cells from 3- (BSC3; n = 3) and 11- (BSC11; n = 3) month -old commercial angus steers. Cells were cultured and collected at zero, 12, 24, and 48 hours to characterize temporal expression and secretion from undifferentiated and differentiated cells. The expression of SPARC was higher in the undifferentiated (p = 0.04) and differentiated (p = 0.07) BSC11 than BSC3. The same was observed with protein secretion from undifferentiated (p <0.0001) BSC11 compared to BSC3. Protein secretion of FGF-21 was higher in undifferentiated BSC11 (p < 0.0001) vs. BSC3. DCN expression was higher in differentiated BSC11 (p = 0.006) vs. BSC3. Comparing undifferentiated vs. differentiated BSC, MSTN expression was higher in differentiated BSC3 (p ≤ 0.001) for 0, 12, and 24 hours and in BSC11 (p ≤ 0.03) for 0, 12, 24, and 48 hours. There is also a change over time for SPARC expression (p ≤ 0.03) in undifferentiated and differentiated BSC and protein secretion (p < 0.0001) in undifferentiated BSC, as well as FGF-21 expression (p = 0.007) in differentiated BSC. This study confirms SPARC, FGF-21, and DCN are secreted, and SPARC, FGF-21, MSTN, and DCN are expressed in primary bovine muscle cells with age and temporal differences.


Sujet(s)
Différenciation cellulaire , Décorine , Facteurs de croissance fibroblastique , Ostéonectine , Animaux , Bovins , Ostéonectine/métabolisme , Ostéonectine/génétique , Facteurs de croissance fibroblastique/métabolisme , Décorine/métabolisme , Cellules cultivées , Mâle , Cellules satellites du muscle squelettique/métabolisme , Cellules satellites du muscle squelettique/cytologie , Vieillissement/métabolisme , Myostatine/métabolisme , Muscles squelettiques/métabolisme , Muscles squelettiques/cytologie
3.
BMC Res Notes ; 17(1): 205, 2024 Jul 26.
Article de Anglais | MEDLINE | ID: mdl-39061110

RÉSUMÉ

OBJECTIVE: Insertion and deletion (indel) analysis of CRISPR-Cas guide RNAs (gRNAs) is crucial in gene editing to assess gRNA efficiency and indel frequency. This study evaluates the utility of CRISPResso2 with Oxford Nanopore sequencing data (nCRISPResso2) for gRNA indel screening, compared to two common Sanger sequencing-based methods, TIDE and ICE. To achieve this, sheep and horse fibroblasts were transfected with Cas9 and a gRNA targeting the myostatin (MSTN) gene. DNA was subsequently extracted, and PCR products exceeding 600 bp were sequenced using both Sanger and Nanopore sequencing. Indel profiling was then conducted using TIDE, ICE, and nCRISPResso2. RESULTS: Comparison revealed close correspondence in indel formation among methods. For the sheep MSTN gRNA, indel percentages were 52%, 58%, and 64% for TIDE, ICE, and nCRISPResso2, respectively. Horse MSTN gRNA showed 81%, 87%, and 86% edited amplicons for TIDE, ICE, and nCRISPResso2. The frequency of each type of indel was also comparable among the three methods, with nCRISPResso2 and ICE aligning the closest. nCRISPResso2 offers a viable alternative for CRISPR-Cas gRNA indel screening, especially with large amplicons unsuitable for Illumina sequencing. CRISPResso2's compatibility with Nanopore data enables cost-effective and efficient indel profiling, yielding results comparable to common Sanger sequencing-based methods.


Sujet(s)
Systèmes CRISPR-Cas , Édition de gène , Mutation de type INDEL , Myostatine , Séquençage par nanopores , , Systèmes CRISPR-Cas/génétique , Animaux , /génétique , Séquençage par nanopores/méthodes , Ovis/génétique , Equus caballus/génétique , Édition de gène/méthodes , Myostatine/génétique
4.
Genes (Basel) ; 15(7)2024 Jul 15.
Article de Anglais | MEDLINE | ID: mdl-39062700

RÉSUMÉ

Tibetan sheep are vital to the ecosystem and livelihood of the Tibetan Plateau; however, traditional breeding methods limit their production and growth. Modern molecular breeding techniques are required to improve these traits. This study identified a single nucleotide polymorphism (SNP) in myostatin (MSTN) and Callipyge in Tibetan sheep. The findings indicated notable associations between MSTN genotypes and growth traits including birth weight (BW), body length (BL), chest width (ChW), and chest circumference (ChC), as well as a particularly strong association with cannon circumference (CaC) at 2 months of age. Conversely, Callipyge polymorphisms did not have a significant impact on Tibetan sheep. Moreover, the analyses revealed a significant association between sex and BW or hip width (HW) at 2 months of age and ChW, ChC, and CaC at 4 months of age. Furthermore, the study's results suggested that the genotype of MSTN as a GA was associated with a notable sex effect on BW, while the genotype of Callipyge (CC) showed a significant impact of sex on CaC at 2 months of age. These results indicated that the SNP of MSTN could potentially serve as a molecular marker for early growth traits in Tibetan sheep.


Sujet(s)
Myostatine , Polymorphisme de nucléotide simple , Animaux , Myostatine/génétique , Ovis/génétique , Ovis/croissance et développement , Femelle , Mâle , Tibet , Génotype , Phénotype , Poids de naissance/génétique , Sélection
5.
Front Endocrinol (Lausanne) ; 15: 1418177, 2024.
Article de Anglais | MEDLINE | ID: mdl-39006362

RÉSUMÉ

Background: Exercise-induced cytokines involved in controlling body composition include myostatin (MST) and follistatin (FST), both of which are influenced by physical activity. This study investigated changes in body composition and physical activity during a weight loss program, as well as the impact on serum MST and FST levels at various weight loss rates. Methods: A total of 126 patients with obesity who completed a 6-month weight loss program were divided into three groups based on weight loss rate (%): low (< 3%), middle (3-10%), and high (≥10%). The International Physical Activity Questionnaire was used for assessing physical activity, whereas dual X-ray absorptiometry was used to determine body composition. Serum MST and FST levels were measured using the enzyme-linked immunosorbent assay. Results: The middle and high groups showed a significant decrease in percent body fat and a significant increase in percent lean body mass and physical activity. Serum MST levels increased significantly in all three groups, although FST levels reduced significantly only in the middle group. After adjusting for sex and body composition, changes in peak oxygen intake (ß = -0.359) and serum FST levels (ß = -0.461) were identified as independent factors for the change in MST levels in the low group. Sex (ß = -0.420) and changes in MST levels (ß = -0.525) were identified as independent factors for the change in serum FST levels in the low group, whereas in the high group, sitting time (ß = -0.600) during the weight loss program was identified as an independent factor for change in serum FST levels. Conclusion: Serum MST levels in patients with obesity increased significantly following the weight loss program, independent of weight loss rate. In contrast, serum FST levels reduced significantly only in the 3-10% weight loss group. These findings indicate that MST and FST secretion dynamics may fluctuate in response to physical activity, while also reflecting feedback regulation of body composition and metabolism during weight reduction.


Sujet(s)
Composition corporelle , Exercice physique , Follistatine , Myostatine , Obésité , Perte de poids , Humains , Mâle , Myostatine/sang , Myostatine/métabolisme , Femelle , Follistatine/sang , Perte de poids/physiologie , Obésité/sang , Obésité/métabolisme , Adulte d'âge moyen , Adulte , Exercice physique/physiologie , Programmes de perte de poids , Absorptiométrie photonique
6.
Clin Nutr ; 43(7): 1800-1808, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38861892

RÉSUMÉ

BACKGROUND & AIMS: Our study aims to determine whether myostatin (MSTN) is associated with muscle mass and strength in individuals with cancer or obesity, as well as with cancer cachexia (CC) or sarcopenic obesity (SO). METHODS: The ACTICA study included individuals with CC (n = 70) or without CC (NC, n = 73). The MYDIASECRET study included individuals with obesity evaluated before (T0) and 3 months (T3) after bariatric surgery (n = 62). Body composition was assessed using bioelectrical impedance analysis (BIA). Skeletal muscle mass (SMM) and appendicular SMM (ASMM) were calculated from Janssen's and Sergi's equations, respectively, and expressed as indexes (SMMI and ASMMI). Handgrip strength (HGS) was assessed using a Jamar hand-held dynamometer. MSTN plasma levels were measured using ELISA. Spearman's coefficient was used to correlate MSTN with muscle mass and strength. Receiver operating characteristic (ROC) curve analysis was performed to identify an optimal MSTN cutoff level for the prediction of CC or SO. RESULTS: In the ACTICA study, muscle mass and strength were lower in CC individuals than in NC individuals (SMMI: 8.0 kg/m2vs 9.0 kg/m2, p = 0.004; ASMMI: 6.2 kg/m2vs 7.2 kg/m2, p < 0.001; HGS: 28 kg vs 38 kg, p < 0.001). MSTN was also lower in CC individuals than in NC individuals (1434 pg/mL vs 2149 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN (SMMI: R = 0.500, p < 0.001; ASMMI: R = 0.479, p < 0.001; HGS: R = 0.495, p < 0.001). ROC curve analysis showed a MSTN cutoff level of 1548 pg/mL (AUC 0.684, sensitivity 57%, specificity 75%, p < 0.001) for the prediction of CC. In the MYDIASECRET study, muscle mass and strength were reduced at T3 (SMMI: -8%, p < 0.001; ASMMI: -12%, p < 0.001; HGS: -6%, p = 0.005). MSTN was also reduced at T3 (1773 pg/mL vs 2582 pg/mL, p < 0.001). Muscle mass and strength were positively correlated with MSTN at T0 and T3 (SMMI-T0: R = 0.388, p = 0.002; SMMI-T3: R = 0.435, p < 0.001; HGS-T0: R = 0.337, p = 0.007; HGS-T3: R = 0.313, p = 0.013). ROC curve analysis showed a MSTN cutoff level of 4225 pg/mL (AUC 0.835, sensitivity 98%, specificity 100%, p = 0.014) for the prediction of SO at T3. CONCLUSIONS: MSTN is positively correlated with muscle mass and strength in individuals with cancer or obesity, suggesting its potential use as a biomarker of muscle mass and strength. The ROC curve analysis suggests the potential use of MSTN as a screening tool for CC and SO.


Sujet(s)
Marqueurs biologiques , Cachexie , Force de la main , Muscles squelettiques , Myostatine , Tumeurs , Obésité , Sarcopénie , Humains , Myostatine/sang , Mâle , Femelle , Tumeurs/sang , Tumeurs/complications , Tumeurs/physiopathologie , Muscles squelettiques/physiopathologie , Adulte d'âge moyen , Obésité/sang , Obésité/physiopathologie , Obésité/complications , Cachexie/sang , Cachexie/étiologie , Cachexie/physiopathologie , Marqueurs biologiques/sang , Sarcopénie/sang , Sarcopénie/étiologie , Sarcopénie/physiopathologie , Force de la main/physiologie , Composition corporelle , Sujet âgé , Force musculaire/physiologie , Adulte , Impédance électrique
7.
Pflugers Arch ; 476(8): 1221-1233, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38916665

RÉSUMÉ

This study investigated the effect of a resistance training (RT) period at terrestrial (HH) and normobaric hypoxia (NH) on both muscle hypertrophy and maximal strength development with respect to the same training in normoxia (N). Thirty-three strength-trained males were assigned to N (FiO2 = 20.9%), HH (2,320 m asl) or NH (FiO2 = 15.9%). The participants completed an 8-week RT program (3 sessions/week) of a full body routine. Muscle thickness of the lower limb and 1RM in back squat were assessed before and after the training program. Blood markers of stress, inflammation (IL-6) and muscle growth (% active mTOR, myostatin and miRNA-206) were measured before and after the first and last session of the program. Findings revealed all groups improved 1RM, though this was most enhanced by RT in NH (p = 0.026). According to the moderate to large excess of the exercise-induced stress response (lactate and Ca2+) in HH and N, results only displayed increases in muscle thickness in these two conditions over NH (ES > 1.22). Compared with the rest of the environmental conditions, small to large increments in % active mTOR were only found in HH, and IL-6, myostatin and miR-206 in NH throughout the training period. In conclusion, the results do not support the expected additional benefit of RT under hypoxia compared to N on muscle growth, although it seems to favour gains in strength. The greater muscle growth achieved in HH over NH confirms the impact of the type of hypoxia on the outcomes.


Sujet(s)
Hypoxie , Force musculaire , Muscles squelettiques , Myostatine , Entraînement en résistance , Mâle , Humains , Entraînement en résistance/méthodes , Hypoxie/métabolisme , Hypoxie/physiopathologie , Muscles squelettiques/métabolisme , Muscles squelettiques/croissance et développement , Myostatine/métabolisme , Adulte , Force musculaire/physiologie , microARN/métabolisme , microARN/génétique , Sérine-thréonine kinases TOR/métabolisme , Interleukine-6/métabolisme , Interleukine-6/sang , Jeune adulte , Développement musculaire
8.
Int J Mol Sci ; 25(11)2024 May 24.
Article de Anglais | MEDLINE | ID: mdl-38891908

RÉSUMÉ

Chronic inflammation causes muscle wasting. Because most inflammatory cytokine signals are mediated via TGF-ß-activated kinase-1 (TAK1) activation, inflammatory cytokine-induced muscle wasting may be ameliorated by the inhibition of TAK1 activity. The present study was undertaken to clarify whether TAK1 inhibition can ameliorate inflammation-induced muscle wasting. SKG/Jcl mice as an autoimmune arthritis animal model were treated with a small amount of mannan as an adjuvant to enhance the production of TNF-α and IL-1ß. The increase in these inflammatory cytokines caused a reduction in muscle mass and strength along with an induction of arthritis in SKG/Jcl mice. Those changes in muscle fibers were mediated via the phosphorylation of TAK1, which activated the downstream signaling cascade via NF-κB, p38 MAPK, and ERK pathways, resulting in an increase in myostatin expression. Myostatin then reduced the expression of muscle proteins not only via a reduction in MyoD1 expression but also via an enhancement of Atrogin-1 and Murf1 expression. TAK1 inhibitor, LL-Z1640-2, prevented all the cytokine-induced changes in muscle wasting. Thus, TAK1 inhibition can be a new therapeutic target of not only joint destruction but also muscle wasting induced by inflammatory cytokines.


Sujet(s)
Cytokines , MAP Kinase Kinase Kinases , Amyotrophie , Animaux , MAP Kinase Kinase Kinases/métabolisme , MAP Kinase Kinase Kinases/antagonistes et inhibiteurs , Amyotrophie/métabolisme , Amyotrophie/anatomopathologie , Amyotrophie/étiologie , Amyotrophie/traitement médicamenteux , Souris , Cytokines/métabolisme , Faiblesse musculaire/métabolisme , Faiblesse musculaire/traitement médicamenteux , Myostatine/métabolisme , Myostatine/antagonistes et inhibiteurs , Protéines du muscle/métabolisme , Facteur de nécrose tumorale alpha/métabolisme , Facteur de transcription NF-kappa B/métabolisme , Inflammation/métabolisme , Inflammation/anatomopathologie , Inflammation/traitement médicamenteux , Transduction du signal/effets des médicaments et des substances chimiques , Protéines à motif tripartite/métabolisme , Protéines à motif tripartite/génétique , Modèles animaux de maladie humaine , Interleukine-1 bêta/métabolisme , Phosphorylation/effets des médicaments et des substances chimiques , Muscles squelettiques/métabolisme , Muscles squelettiques/anatomopathologie , Muscles squelettiques/effets des médicaments et des substances chimiques , Zéaralénone/pharmacologie , Zéaralénone/analogues et dérivés
9.
BMC Genomics ; 25(1): 637, 2024 Jun 26.
Article de Anglais | MEDLINE | ID: mdl-38926663

RÉSUMÉ

Dynamic metabolic reprogramming occurs at different stages of myogenesis and contributes to the fate determination of skeletal muscle satellite cells (MuSCs). Accumulating evidence suggests that mutations in myostatin (MSTN) have a vital role in regulating muscle energy metabolism. Here, we explored the metabolic reprogramming in MuSCs and myotube cells in MSTN and FGF5 dual-gene edited sheep models prepared previously, and also focused on the metabolic alterations during myogenic differentiation of MuSCs. Our study revealed that the pathways of nucleotide metabolism, pantothenate and CoA biosynthesis were weakened, while the unsaturated fatty acids biosynthesis were strengthened during myogenic differentiation of sheep MuSCs. The MSTN and FGF5 dual-gene editing mainly inhibited nucleotide metabolism and biosynthesis of unsaturated fatty acids in sheep MuSCs, reduced the number of lipid droplets in per satellite cell, and promoted the pentose phosphate pathway, and the interconversion of pentose and glucuronate. The MSTN and FGF5 dual-gene editing also resulted in the inhibition of nucleotide metabolism and TCA cycle pathway in differentiated myotube cells. The differential metabolites we identified can be characterized as biomarkers of different cellular states, and providing a new reference for MSTN and FGF5 dual-gene editing in regulation of muscle development. It may also provide a reference for the development of muscle regeneration drugs targeting biomarkers.


Sujet(s)
Facteur de croissance fibroblastique de type 5 , Édition de gène , Développement musculaire , Myostatine , Animaux , Myostatine/génétique , Myostatine/métabolisme , Développement musculaire/génétique , Ovis , Facteur de croissance fibroblastique de type 5/génétique , Facteur de croissance fibroblastique de type 5/métabolisme , Différenciation cellulaire , Cellules satellites du muscle squelettique/métabolisme , Cellules satellites du muscle squelettique/cytologie , Fibres musculaires squelettiques/métabolisme , Fibres musculaires squelettiques/cytologie
10.
Nutrients ; 16(11)2024 May 29.
Article de Anglais | MEDLINE | ID: mdl-38892621

RÉSUMÉ

BACKGROUND: Recently, many studies have been devoted to discovering nutrients for exercise-like effects. Resistance exercise and the intake of essential amino acids (EAAs) are known to be factors that can affect muscle mass and strength improvement. The purpose of this study was to investigate changes in muscle quality, myokines, and inflammation in response to resistance exercise and EAA supplementation. METHODS: Thirty-four males volunteered to participate in this study. They were assigned to four groups: (1) placebo (CO), (2) resistance exercise (RE), (3) EAA supplementation, and (4) RE + EAA supplementation. Body composition, muscle quality, myokines, and inflammation were measured at baseline and four weeks after treatment. RESULTS: Lean body fat had decreased in both RE and RE + EAA groups. Lean body mass had increased in only the RE + EAA group. In all groups except for CO, irisin, myostatin A, and TNF-α levels had decreased. The grip strength of the right hand and trunk flexion peak torque increased in the RE group. The grip strength of the left hand, trunk flexion peak torque, and knee flexion peak torque of the left leg were increased in RE + EAA. CONCLUSIONS: RE, EAA, and RE + EAA could effectively improve the muscle quality, myokine, and inflammation factors of young adult males. This finding highlights the importance of resistance exercise and amino acid intake.


Sujet(s)
Acides aminés essentiels , Composition corporelle , Compléments alimentaires , Inflammation , Muscles squelettiques , Entraînement en résistance , Humains , Mâle , Jeune adulte , Muscles squelettiques/physiologie , Muscles squelettiques/métabolisme , Acides aminés essentiels/administration et posologie , Facteur de nécrose tumorale alpha/sang , Adulte , Force musculaire/effets des médicaments et des substances chimiques , Force de la main/physiologie , Myostatine/métabolisme , Fibronectines ,
11.
Poult Sci ; 103(8): 103951, 2024 Aug.
Article de Anglais | MEDLINE | ID: mdl-38909511

RÉSUMÉ

As an anti-myogenic factor, the myostatin (MSTN) gene was mainly considered as a genetic marker to improve meat production. Moreover, an additional effect of the MSTN mutation on reducing fat deposition in various farm animals suggested a potential application of the MSTN gene on regulating fat deposition in poultry species. Although increase in muscle mass resulted from muscle hyperplasia in the MSTN mutant quail, cellular mechanism behind the decrease in fat deposition was not investigated in the quail model. In the current study, to investigate sexual dimorphic association between fat deposition and Mstn mutation in quail, leg and abdominal fat pads from 4-month-old male and female quail were histologically analyzed. Interestingly, abdominal and leg fat pad weights were significantly decreased by the MSTN mutation only in female quail, but not in male quail, showing sexual dimorphism in regulating fat deposition by the MSTN mutation in quail. Histological analysis also revealed that fat cell sizes of leg and abdominal fats were significantly reduced only in female groups aligning with the decreased fat pad weights. Sexual dimorphic effect of the MSTN mutation on fat cell hypotrophy and reduced fat pad weights in quail provided an important scientific finding to be considered on the usage of the MSTN gene as a genetic marker to reduce fat deposition in poultry species.


Sujet(s)
Tissu adipeux , Coturnix , Mutation , Myostatine , Animaux , Myostatine/génétique , Myostatine/métabolisme , Femelle , Mâle , Coturnix/génétique , Coturnix/physiologie , Tissu adipeux/métabolisme , Caractères sexuels , Protéines aviaires/génétique , Protéines aviaires/métabolisme
12.
Int J Mol Sci ; 25(10)2024 May 12.
Article de Anglais | MEDLINE | ID: mdl-38791317

RÉSUMÉ

The myostatin (MSTN) gene also regulates the developmental balance of skeletal muscle after birth, and has long been linked to age-related muscle wasting. Many rodent studies have shown a correlation between MSTN and age-related diseases. It is unclear how MSTN and age-associated muscle loss in other animals are related. In this study, we utilized MSTN gene-edited bovine skeletal muscle cells to investigate the mechanisms relating to MSTN and muscle cell senescence. The expression of MSTN was higher in older individuals than in younger individuals. We obtained consecutively passaged senescent cells and performed senescence index assays and transcriptome sequencing. We found that senescence hallmarks and the senescence-associated secretory phenotype (SASP) were decreased in long-term-cultured myostatin inactivated (MT-KO) bovine skeletal muscle cells (bSMCs). Using cell signaling profiling, MSTN was shown to regulate the SASP, predominantly through the cycle GMP-AMP synthase-stimulator of antiviral genes (cGAS-STING) pathway. An in-depth investigation by chromatin immunoprecipitation (ChIP) analysis revealed that MSTN influenced three prime repair exonuclease 1 (TREX1) expression through the SMAD2/3 complex. The downregulation of MSTN contributed to the activation of the MSTN-SMAD2/3-TREX1 signaling axis, influencing the secretion of SASP, and consequently delaying the senescence of bSMCs. This study provided valuable new insight into the role of MSTN in cell senescence in large animals.


Sujet(s)
Vieillissement de la cellule , Myostatine , Animaux , Myostatine/génétique , Myostatine/métabolisme , Bovins , Vieillissement de la cellule/génétique , Exodeoxyribonucleases/métabolisme , Exodeoxyribonucleases/génétique , Transduction du signal , Fibres musculaires squelettiques/métabolisme , Muscles squelettiques/métabolisme , Phosphoprotéines/métabolisme , Phosphoprotéines/génétique , Cellules cultivées
13.
J Physiol ; 602(12): 2839-2854, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38748517

RÉSUMÉ

Loss of muscle mass and function induced by sepsis contributes to physical inactivity and disability in intensive care unit patients. Limiting skeletal muscle deconditioning may thus be helpful in reducing the long-term effect of muscle wasting in patients. We tested the hypothesis that invalidation of the myostatin gene, which encodes a powerful negative regulator of skeletal muscle mass, could prevent or attenuate skeletal muscle wasting and improve survival of septic mice. Sepsis was induced by caecal ligature and puncture (CLP) in 13-week-old C57BL/6J wild-type and myostatin knock-out male mice. Survival rates were similar in wild-type and myostatin knock-out mice seven days after CLP. Loss in muscle mass was also similar in wild-type and myostatin knock-out mice 4 and 7 days after CLP. The loss in muscle mass was molecularly supported by an increase in the transcript level of E3-ubiquitin ligases and autophagy-lysosome markers. This transcriptional response was blunted in myostatin knock-out mice. No change was observed in the protein level of markers of the anabolic insulin/IGF1-Akt-mTOR pathway. Muscle strength was similarly decreased in wild-type and myostatin knock-out mice 4 and 7 days after CLP. This was associated with a modified expression of genes involved in ion homeostasis and excitation-contraction coupling, suggesting that a long-term functional recovery following experimental sepsis may be impaired by a dysregulated expression of molecular determinants of ion homeostasis and excitation-contraction coupling. In conclusion, myostatin gene invalidation does not provide any benefit in preventing skeletal muscle mass loss and strength in response to experimental sepsis. KEY POINTS: Survival rates are similar in wild-type and myostatin knock-out mice seven days after the induction of sepsis. Loss in muscle mass and muscle strength are similar in wild-type and myostatin knock-out mice 4 and 7 days after the induction of an experimental sepsis. Despite evidence of a transcriptional regulation, the protein level of markers of the anabolic insulin/IGF1-Akt-mTOR pathway remained unchanged. RT-qPCR analysis of autophagy-lysosome pathway markers indicates that activity of the pathway may be altered by experimental sepsis in wild-type and myostatin knock-out mice. Experimental sepsis induces greater variations in the mRNA levels of wild-type mice than those of myostatin knock-out mice, without providing any significant catabolic resistance or functional benefits.


Sujet(s)
Souris de lignée C57BL , Souris knockout , Muscles squelettiques , Myostatine , Sepsie , Animaux , Myostatine/génétique , Myostatine/métabolisme , Sepsie/génétique , Sepsie/métabolisme , Muscles squelettiques/métabolisme , Mâle , Souris , Autophagie , Amyotrophie/génétique , Amyotrophie/métabolisme , Force musculaire , Sérine-thréonine kinases TOR/métabolisme , Sérine-thréonine kinases TOR/génétique , Protéines proto-oncogènes c-akt/métabolisme , Protéines proto-oncogènes c-akt/génétique
14.
Gen Comp Endocrinol ; 355: 114550, 2024 Sep 01.
Article de Anglais | MEDLINE | ID: mdl-38768928

RÉSUMÉ

Skeletal muscles serve both in movement and as endocrine organs. Myokines secreted by skeletal muscles activate biological functions within muscles and throughout the body via autocrine, paracrine, and/or endocrine pathways. Skeletal muscle atrophy can influence myokine expression and secretion, while myokines can impact the structure and function of skeletal muscles. Regulating the expression and secretion of myokines through the pharmacological approach is a strategy for alleviating skeletal muscle atrophy. Natural products possess complex structures and chemical properties. Previous studies have demonstrated that various natural products exert beneficial effects on skeletal muscle atrophy. This article reviewed the regulatory effects of natural products on myokines and summarized the research progress on skeletal muscle atrophy associated with myokine regulation. The focus is on how small-molecule natural products affect the regulation of interleukin 6 (IL-6), irisin, myostatin, IGF-1, and FGF-21 expression. We contend that the development of small-molecule natural products targeting the regulation of myokines holds promise in combating skeletal muscle atrophy.


Sujet(s)
Produits biologiques , Muscles squelettiques , Amyotrophie , Amyotrophie/métabolisme , Amyotrophie/traitement médicamenteux , Amyotrophie/anatomopathologie , Produits biologiques/pharmacologie , Produits biologiques/usage thérapeutique , Humains , Animaux , Muscles squelettiques/métabolisme , Muscles squelettiques/effets des médicaments et des substances chimiques , Muscles squelettiques/anatomopathologie , Myostatine/métabolisme , Facteur de croissance IGF-I/métabolisme , Interleukine-6/métabolisme , Facteurs de croissance fibroblastique/métabolisme ,
15.
Mar Biotechnol (NY) ; 26(3): 599-608, 2024 Jun.
Article de Anglais | MEDLINE | ID: mdl-38683458

RÉSUMÉ

Myostatin (MSTN, also known as growth differentiation factor-8 (GDF-8)), a member of the transforming growth factor ß (TGF-ß) superfamily, functions as a negative regulator of skeletal muscle development and growth. However, it is also expressed in a wide range of tissues in fish and thus may have more diverse roles in this group than in mammals. In this study, we assessed the genome-wide transcriptional expression pattern associated with the CRISPR/Cas9-mutated MSTN gene in the olive flounder (Paralichthys olivaceus) in association with changes in cell proliferation and transportation processes. There were no differences in the hepatosomatic index, and the growth of male and female fish increased in the F1 progeny of the MSTN mutants. Furthermore, the histopathological analysis showed that myostatin editing resulted in a 41.24% increase in back muscle growth and 46.92% increase in belly muscle growth in male flounder compared with normal flounder, and a 16.01% increase in back muscle growth and 14.26% increase in belly muscle growth in female flounder compared with normal flounder. This study demonstrates that editing of the myostatin gene enhances muscle growth in olive flounder, with a notably more pronounced effect observed in males. Consequently, myostatin-edited male flounder could represent a valuable asset for the flounder aquaculture industry.


Sujet(s)
Pleuronectidae , Muscles squelettiques , Myostatine , Animaux , Myostatine/génétique , Myostatine/métabolisme , Mâle , Femelle , Pleuronectidae/génétique , Pleuronectidae/croissance et développement , Pleuronectidae/métabolisme , Muscles squelettiques/métabolisme , Muscles squelettiques/croissance et développement , Développement musculaire/génétique , Édition de gène , Protéines de poisson/génétique , Protéines de poisson/métabolisme , Systèmes CRISPR-Cas , Mutation
16.
Sci China Life Sci ; 67(7): 1441-1454, 2024 Jul.
Article de Anglais | MEDLINE | ID: mdl-38561484

RÉSUMÉ

The basic mechanism of heterosis has not been systematically and completely characterized. In previous studies, we obtained three economically important fishes that exhibit rapid growth, WR (WCC ♀ × RCC ♂), WR-II (WR ♀ × WCC ♂), and WR-III (WR-II ♀ × 4nAU ♂), through distant hybridization. However, the mechanism underlying this rapid growth remains unclear. In this study, we found that WR, WR-II, and WR-III showed muscle hypertrophy and higher muscle protein and fat contents compared with their parent species (RCC and WCC). Candidate genes responsible for this rapid growth were then obtained through an analysis of 12 muscle transcriptomes. Notably, the mRNA level of mstnb (myostatin b), which is a negative regulator of myogenesis, was significantly reduced in WR, WR-II, and WR-III compared with the parent species. To verify the function of mstnb, a mstnb-deficient mutant RCC line was generated using the CRISPR-Cas9 technique. The average body weight of mstnb-deficient RCC at 12 months of age was significantly increased by 29.57% compared with that in wild-type siblings. Moreover, the area and number of muscle fibers were significantly increased in mstnb-deficient RCC, indicating hypertrophy and hyperplasia. Furthermore, the muscle protein and fat contents were significantly increased in mstnb-deficient RCC. The molecular regulatory mechanism of mstnb was then revealed by transcription profiling, which showed that genes related to myogenesis (myod, myog, and myf5), protein synthesis (PI3K-AKT-mTOR), and lipogenesis (pparγ and fabp3) were highly activated in hybrid fishes and mstnb-deficient RCC. This study revealed that low expression or deficiency of mstnb regulates somatic growth by promoting myogenesis, protein synthesis, and lipogenesis in hybrid fishes and mstnb-deficient RCC, which provides evidence for the molecular mechanism of heterosis via distant hybridization.


Sujet(s)
Hybridation génétique , Développement musculaire , Myostatine , Animaux , Myostatine/génétique , Myostatine/métabolisme , Développement musculaire/génétique , Vigueur hybride/génétique , Mâle , Poissons/génétique , Poissons/croissance et développement , Poissons/métabolisme , Femelle , Transcriptome , Protéines du muscle/génétique , Protéines du muscle/métabolisme , Muscles squelettiques/métabolisme , Muscles squelettiques/croissance et développement , Protéines de poisson/génétique , Protéines de poisson/métabolisme
17.
Gen Comp Endocrinol ; 353: 114513, 2024 07 01.
Article de Anglais | MEDLINE | ID: mdl-38604437

RÉSUMÉ

Skeletal muscle, comprising a significant proportion (40 to 50 percent) of total body weight in humans, plays a critical role in maintaining normal physiological conditions. Muscle atrophy occurs when the rate of protein degradation exceeds protein synthesis. Sarcopenia refers to age-related muscle atrophy, while cachexia represents a more complex form of muscle wasting associated with various diseases such as cancer, heart failure, and AIDS. Recent research has highlighted the involvement of signaling pathways, including IGF1-Akt-mTOR, MuRF1-MAFbx, and FOXO, in regulating the delicate balance between muscle protein synthesis and breakdown. Myostatin, a member of the TGF-ß superfamily, negatively regulates muscle growth and promotes muscle atrophy by activating Smad2 and Smad3. It also interacts with other signaling pathways in cachexia and sarcopenia. Inhibition of myostatin has emerged as a promising therapeutic approach for sarcopenia and cachexia. Additionally, other TGF-ß family members, such as TGF-ß1, activin A, and GDF11, have been implicated in the regulation of skeletal muscle mass. Furthermore, myostatin cooperates with these family members to impair muscle differentiation and contribute to muscle loss. This review provides an overview of the significance of myostatin and other TGF-ß signaling pathway members in muscular dystrophy, sarcopenia, and cachexia. It also discusses potential novel therapeutic strategies targeting myostatin and TGF-ß signaling for the treatment of muscle atrophy.


Sujet(s)
Cachexie , Amyotrophie , Myostatine , Tumeurs , Sarcopénie , Transduction du signal , Facteur de croissance transformant bêta , Humains , Cachexie/métabolisme , Cachexie/anatomopathologie , Amyotrophie/métabolisme , Amyotrophie/anatomopathologie , Sarcopénie/métabolisme , Sarcopénie/anatomopathologie , Transduction du signal/physiologie , Tumeurs/métabolisme , Tumeurs/complications , Tumeurs/anatomopathologie , Facteur de croissance transformant bêta/métabolisme , Myostatine/métabolisme , Animaux , Muscles squelettiques/métabolisme , Muscles squelettiques/anatomopathologie
18.
Arch Pharm Res ; 47(4): 301-324, 2024 Apr.
Article de Anglais | MEDLINE | ID: mdl-38592582

RÉSUMÉ

Sarcopenia is a multifactorial condition characterized by loss of muscle mass. It poses significant health risks in older adults worldwide. Both pharmacological and non-pharmacological approaches are reported to address this disease. Certain dietary patterns, such as adequate energy intake and essential amino acids, have shown positive outcomes in preserving muscle function. Various medications, including myostatin inhibitors, growth hormones, and activin type II receptor inhibitors, have been evaluated for their effectiveness in managing sarcopenia. However, it is important to consider the variable efficacy and potential side effects associated with these treatments. There are currently no drugs approved by the Food and Drug Administration for sarcopenia. The ongoing research aims to develop more effective strategies in the future. Our review of research on disease mechanisms and drug development will be a valuable contribution to future research endeavors.


Sujet(s)
Sarcopénie , Sarcopénie/traitement médicamenteux , Sarcopénie/métabolisme , Sarcopénie/thérapie , Humains , Animaux , Muscles squelettiques/effets des médicaments et des substances chimiques , Muscles squelettiques/métabolisme , Myostatine/antagonistes et inhibiteurs , Myostatine/métabolisme , Développement de médicament/méthodes
19.
Int J Mol Sci ; 25(8)2024 Apr 13.
Article de Anglais | MEDLINE | ID: mdl-38673892

RÉSUMÉ

Skeletal muscle plays a critical role in metabolic diseases, such as obesity and type 2 diabetes mellitus (T2DM). Muscle atrophy, characterized by a decrease in muscle mass and function, occurs due to an imbalance between the rates of muscle protein synthesis and degradation. This study aimed to investigate the molecular mechanisms that lead to muscle atrophy in obese and T2DM mouse models. Additionally, the effect of nerve growth factor (NGF) on the protein synthesis and degradation pathways was examined. Male mice were divided into three groups: a control group that was fed a standard chow diet, and two experimental groups that were fed a Western diet. After 8 weeks, the diabetic group was injected with streptozotocin to induce T2DM. Each group was then further divided into NGF-treated or non-treated control group. In the gastrocnemius muscles of the Western diet group, increased expressions of myostatin, autophagy markers, and ubiquitin ligases were observed. Skeletal muscle tissue morphology indicated signs of muscle atrophy in both obese and diabetic mice. The NGF-treated group showed a prominent decrease in the protein levels of myostatin and autophagy markers. Furthermore, the NGF-treated group showed an increased Cyclin D1 level. Western diet-induced obesity and T2DM may be linked to muscle atrophy through upregulation of myostatin and subsequent increase in the ubiquitin and autophagy systems. Moreover, NGF treatment may improve muscle protein synthesis and cell cycling.


Sujet(s)
Diabète expérimental , Diabète de type 2 , Muscles squelettiques , Amyotrophie , Facteur de croissance nerveuse , Obésité , Animaux , Mâle , Souris , Autophagie/effets des médicaments et des substances chimiques , Diabète expérimental/métabolisme , Diabète expérimental/anatomopathologie , Diabète expérimental/complications , Diabète de type 2/métabolisme , Diabète de type 2/complications , Diabète de type 2/anatomopathologie , Régime occidental , Souris de lignée C57BL , Muscles squelettiques/métabolisme , Muscles squelettiques/anatomopathologie , Muscles squelettiques/effets des médicaments et des substances chimiques , Amyotrophie/métabolisme , Amyotrophie/étiologie , Amyotrophie/anatomopathologie , Myostatine/métabolisme , Facteur de croissance nerveuse/métabolisme , Obésité/métabolisme , Obésité/complications , Obésité/anatomopathologie
20.
J Frailty Aging ; 13(2): 82-90, 2024.
Article de Anglais | MEDLINE | ID: mdl-38616363

RÉSUMÉ

BACKGROUND: Population aging might increase the prevalence of undernutrition in older people, which increases the risk of frailty. Numerous studies have indicated that myokines are released by skeletal myocytes in response to muscular contractions and might be associated with frailty. This study aimed to evaluate whether myokines are biomarkers of frailty in older inpatients with undernutrition. METHODS: The frailty biomarkers were extracted from the Gene Expression Omnibus and Genecards datasets. Relevant myokines and health-related variables were assessed in 55 inpatients aged ≥ 65 years from the Peking Union Medical College Hospital prospective longitudinal frailty study. Serum was prepared for enzyme-linked immunosorbent assay using the appropriate kits. Correlations between biomarkers and frailty status were calculated by Spearman's correlation analysis. Multiple linear regression was performed to investigate the association between factors and frailty scores. RESULTS: The prevalence of frailty was 13.21%. The bioinformatics analysis indicated that leptin, adenosine 5'-monophosphate-activated protein kinase (AMPK), irisin, decorin, and myostatin were potential biomarkers of frailty. The frailty group had significantly higher concentrations of leptin, AMPK, and MSTN than the robust group (p < 0.05). AMPK was significantly positively correlated with frailty (p < 0.05). The pre-frailty and frailty groups had significantly lower concentrations of irisin than the robust group (p < 0.05), whereas the DCN concentration did not differ among the groups. Multiple linear regression suggested that the 15 factors influencing the coefficients of association, the top 50% were the ADL score, MNA-SF score, serum albumin concentration, urination function, hearing function, leptin concentration, GDS-15 score, and MSTN concentration. CONCLUSIONS: Proinflammatory myokines, particularly leptin, myostatin, and AMPK, negatively affect muscle mass and strength in older adults. ADL and nutritional status play major roles in the development of frailty. Our results confirm that identification of frailty relies upon clinical variables, myokine concentrations, and functional parameters, which might enable the identification and monitoring of frailty.


Sujet(s)
Fragilité , Malnutrition , Humains , Sujet âgé , AMP-Activated Protein Kinases , Fibronectines , Fragilité/diagnostic , Fragilité/épidémiologie , Patients hospitalisés , Leptine , , Myostatine , Études prospectives , Malnutrition/diagnostic , Malnutrition/épidémiologie , Marqueurs biologiques
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