Muscle Creatine Research Articles

Effect Of Branched-chain Amino Acid Plus Glucose Supplement Timing On DOMS And Related Indicators After Eccentric Exercise

PURPOSE: Nutrient timing is a strategic approach to maximize training effects, reduce risk of injury, and help with recovery. The present study examined the effect of BCAA plus Glucose on markers of muscle damage and Inflammation after eccentric exercise in male college students. METHODS: 18 healthy college students were divided into control group (PLA) group and supplement (BCAA+G) group randomly. Each group was randomly assigned 4 people for pre-exercise supplementation and 4 people after exercise for the first time, and changed for the second time. Before or after supplementation, volunteers performed an eccentric exercise protocol. Muscle soreness(VAS), creatine kinase (CK), C-reactive protein (CRP) and interleukin-6 (IL-6) and 3-methylhistamine (3MH) assessments were performed before exercise and after 30min, 24, 48 hours. RESULTS: The VAS score of the subjects increased significantly 24 hours after high-intensity eccentric exercise(2.86 vs 1.66, p<.05), and the increase of serum CK level(364.45 vs. 151.02U/L ), CRP(4.77 vs. 3.28mg/L) and IL-6(279.00 vs. 110.63pg/ml) increased significantly(p<.05); BCAA plus G supplement significantly reduced the VAS score(1.27 vs 2.86, p<.05) and CK(258.74 vs. 364.45U/L), CRP(3.75 vs. 4.77mg/L), IL-6(164.09 vs.279.00pg/ml) levels(p<.05), compared with pre-supplementation group, post-supplementation had lower VAS score(1.27 vs. 2.63), CRP(3.75 vs. 4.26mg/L) and IL-6(164.09 vs. 226.66pg/ml) and 3MH(105.07 vs. 131.67umol/L) response at 24 h after eccentric exercise(p<.05). CONCLUSIONS: High-intensity eccentric exercise caused DOMS with the elevation of damage and inflammatory markers as CK, CRP and IL-6. BCAA plus G supplementation can effectively reduce the level of DOMS, decrease muscle damage and inflammatory factors and protein breakdown. Compared with pre-exercise supplementation, post-exercise supplementation has a better effect on reducing inflammatory factors and protein breakdown caused by DOMS.

Resistance Training With Elastic Tubing Improves Muscle Strength, Exercise Capacity, and Post-Exercise Creatine Kinase Clearance in Subjects With COPD.

Among the types of physical exercise, resistance exercises have been gaining significant attention in the COPD population. The aim of this study was to compare effects of conventional resistance training and of training by using elastic tubes on muscle strength, exercise capacity, and creatine kinase clearance in subjects with COPD. Twenty-eight subjects with COPD were randomized into the following: resistance training with the elastic tubing group and resistance training with the weight-machine training group (conventional resistance group), performed 3 times a week for 12 weeks. The subjects were submitted to spirometry, functional exercise capacity (the 6-min walk test), muscle strength (dynamometry), and the repetition maximum test. Differences between the initial and final evaluations (Δ) and the (final - initial evaluations)/initial evaluations ×100 (Δ%) of each group were expressed as mean [95% CI]. Nineteen subjects (FEV1 % predicted, 52 ± 18; years, 65 ± 8) completed the training program. Similar improvements were observed in both modalities on muscle strength (knee extension, Δ%18 [6 to 29]; knee flexion, Δ%35 [17 to 54]; elbow flexion, Δ%28 [9 to 48]; shoulder abduction, Δ%41 [25 to 58] and shoulder flexion, Δ%31 [11 to 51] in the weight-machine training group (conventional resistance group); knee extension, Δ%15 [8 to 21]; knee flexion, Δ%28 [15 to 41]; elbow flexion, Δ%36 [22 to 51]; and shoulder abduction, Δ%43 [32 to 55] and shoulder flexion, Δ%43 [25 to 61] in the elastic tubing group, P < .05 for intra-group analysis and P > .05 for between groups analysis), 6-min walk test (baseline 493 ± 67m vs 12 weeks 526 ± 78 in the weight-machine training group (P = .10); baseline 493 ± 71 vs 12 weeks 524 ± 68 in the elastic tubing group (P < .01), P = .88 between groups). The elastic tubing group had lower accumulated creatine kinase levels between 24 and 72 h ((Δ%-24 [-31 to 16] than subjects in the weight-machine training group Δ%3 [-21 to 28], P = .042 between the groups. Training with elastic resistance provided similar changes in muscle strength and exercise capacity to conventional resistance group in the subjects with COPD. The elastic tubing group had faster creatine kinase clearance after a training session than the weight-machine training group (conventional resistance group). The ease of its application associated with similar training benefits to conventional training supported its application in clinical routine.

Muscle and Systemic Molecular Responses to a Single Flywheel Based Iso-Inertial Training Session in Resistance-Trained Men.

Growing evidence points to the effectiveness of flywheel (FW) based iso-inertial resistance training in improving physical performance capacities. However, molecular adaptations induced by FW exercises are largely unknown. Eight resistance-trained men performed 5 sets of 10 maximal squats on a FW device. Muscle biopsies (fine needle aspiration technique) and blood samples were collected before (t0), and 2 h (t1) after FW exercise. Blood samples were additionally drawn after 24 h (t2) and 48 h (t3). Paired samples t-tests revealed significant increases, at t1, of mRNA expression of the genes involved in inflammation, in both muscle (MCP-1, TNF-α, IL-6) and peripheral blood mononuclear cells (IkB-α, MCP-1). Circulating extracellular vesicles (EVs) and EV-encapsulated miRNA levels (miR-206, miR-146a) significantly increased at t1 as well. Conversely, muscle mRNA level of genes associated with muscle growth/remodeling (IGF-1Ea, cyclin D1, myogenin) decreased at t1. One-way repeated measure ANOVAs, with Bonferroni corrected post-hoc pairwise comparisons, revealed significant increases in plasma concentrations of IL-6 (t1; t2; t3) and muscle creatine kinase (t1; t2), while IGF-1 significantly increased at t2 only. Our findings show that, even in experienced resistance trained individuals, a single FW training session modifies local and systemic markers involved in late structural remodeling and functional adaptation of skeletal muscle.

Syntaxin 4 (STX4) Enrichment in Skeletal Muscle Remediates Insulin Resistance via and Improving Mitochondrial Function

Type 2 diabetes afflicts 10% of the US population and is the result of both peripheral insulin resistance (skeletal muscle and adipose tissue) as well as insulin secretion defects (pancreas). Insulin resistance, also commonly termed ‘pre‐diabetes’ is estimated to impact more than 30% of our population, and is caused by the inability of skeletal muscle to clear excess blood glucose from the circulation. Human skeletal muscle accounts for over 80% of glucose clearance in the body, a process important in maintaining glucose homeostasis. Currently the only therapeutics that directly improve muscle glucose uptake are diet and exercise. However, with only 3% of the population leading a “healthy lifestyle”, including exercise, directed therapeutics are required to restore skeletal muscle function in pre‐diabetics. Several studies have identified correlations between insulin resistance and reduced levels of a SNARE protein named Syntaxin 4 (STX4) in human skeletal muscle. STX4 interacts with other SNARE proteins to facilitate the fusion of glucose transporter 4 (GLUT4) vesicles with the plasma membrane, to then channel extracellular glucose to the interior of the muscle cell, ultimately clearing glucose from the circulation.To further define the function of STX4 in muscle, we developed a doxycycline Tet‐on inducible skeletal muscle specific STX4 overexpressing mouse model, under the muscle creatine kinase promoter (skm‐STX4 mice). Chow fed female mice overexpressing STX4 exhibited enhanced insulin sensitivity and improved glucose tolerance. Serum insulin levels from these mice were also reduced compared to littermate controls, concordant with their improved glucose tolerance. The data recapitulated the global overexpression model that we had previously published, suggesting that skeletal muscle is the primary driver in modulating glucose homeostasis. To establish that enriching STX4 can remediate insulin resistance, male skm‐STX4 mice were fed a 45% high fat diet (HF; to mimic a typical western diet), until they became insulin resistant. Upon establishing pre‐diabetes in the mice, STX4 enrichment was induced in the skeletal muscle (HFD+STX4 mice). Remarkably HFD+STX4 mice had the insulin sensitivity of a chow‐fed mouse, resolving the HFD‐linked insulin resistance in full. Moreover, the HFD+STX4 mice had significantly improved voluntary movement and increased respiratory exchange ratio, indicating increased reliance on carbohydrate rather than fat oxidation. The maximal oxygen consumption rate was also increased in primary myotubes from these HFD+ STX4 mice.Taken together, these results suggest that STX4 enrichment carries the potential as a therapeutic to remedy obesity‐linked insulin resistance, potentially via improving mitochondrial function. These results suggest that STX4 could be a viable therapeutic target for treatment of pre‐diabetes.Support or Funding InformationResearch was supported by the NIH (DK067912, DK102233, and DK112917) to D.C.T and by the H.N. &amp; Frances C. Berger Foundation, and Helen &amp; Payson Chu Fellowships to K.E.MThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Germline or inducible knockout of p300 or CBP in skeletal muscle does not alter insulin sensitivity.

Akt is a critical mediator of insulin-stimulated glucose uptake in skeletal muscle. The acetyltransferases, E1A binding protein p300 (p300) and cAMP response element-binding protein binding protein (CBP) are phosphorylated and activated by Akt, and p300/CBP can acetylate and inactivate Akt, thus giving rise to a possible Akt-p300/CBP axis. Our objective was to determine the importance of p300 and CBP to skeletal muscle insulin sensitivity. We used Cre-LoxP methodology to generate mice with germline [muscle creatine kinase promoter (P-MCK and C-MCK)] or inducible [tamoxifen-activated, human skeletal actin promoter (P-iHSA and C-iHSA)] knockout of p300 or CBP. A subset of P-MCK and C-MCK mice were switched to a calorie-restriction diet (60% of ad libitum intake) or high-fat diet at 10 wk of age. For P-iHSA and C-iHSA mice, knockout was induced at 10 wk of age. At 13-15 wk of age, we measured whole-body energy expenditure, oral glucose tolerance, and/or ex vivo skeletal muscle insulin sensitivity. Although p300 and CBP protein abundance and mRNA expression were reduced 55%-90% in p300 and CBP knockout mice, there were no genotype differences in energy expenditure or fasting glucose and insulin concentrations. Moreover, neither loss of p300 or CBP impacted oral glucose tolerance or skeletal muscle insulin sensitivity, nor did their loss impact alterations in these parameters in response to a calorie restriction or high-fat diet. Muscle-specific loss of either p300 or CBP, be it germline or in adulthood, does not impact energy expenditure, glucose tolerance, or skeletal muscle insulin action.

Effect of body composition on redox homeostasis at rest and in response to exercise: The case of underfat women

ABSTRACTUnderfat individuals have been neglected as a malnourished population in terms of redox homeostasis. The aim of the present study was to evaluate the effect of body composition on redox homeostasis at rest and in response to exercise. Underfat, lean and overfat women, classified according to their BMI and body fat percentage, participated in the study and were subjected to an acute session of eccentric exercise. With regard to muscle function and damage, a significant group × time interaction was found for range of motion (P < .01), isometric peak torque at 90° (P < .01), delayed onset muscle soreness (P < .01) and creatine kinase (P < .05), with the lean group generally exhibiting faster recovery compared to the underfat and overfat groups. With regard to redox homeostasis, a significant group × time interaction was found for F2-isoprostanes, protein carbonyls and glutathione (P < .01 for all biomarkers), with the underfat and overfat groups exhibiting increased resting oxidative stress levels and lower exercise-induced reactive species production . In conclusively, our data underline the importance of normal body composition for redox homeostasis, since underfat and overfat women demonstrate a similar pattern of redox disturbances both at rest and in response to exercise.

Effect of Cold Water Immersion Performed on Successive Days on Physical Performance, Muscle Damage, and Inflammatory, Hormonal, and Oxidative Stress Markers in Volleyball Players.

de Freitas, VH, Ramos, SP, Bara-Filho, MG, Freitas, DGS, Coimbra, DR, Cecchini, R, Guarnier, FA, and Nakamura, FY. Effect of cold water immersion performed on successive days on physical performance, muscle damage, and inflammatory, hormonal, and oxidative stress markers in volleyball players. J Strength Cond Res 33(2): 502-513, 2019-The aim of this study was to investigate the effects of daily cold water immersion (CWI) on physical performance, muscle damage, and inflammatory, hormonal, and oxidative stress markers in volleyball. Six players were submitted to CWI and six players to a placebo, during 5 training days. Thigh circumference, squat jump, and agility were measured on the first, third, and sixth days. On the first and sixth days, blood and saliva were collected for analysis of oxidative stress, muscle damage, and inflammatory and hormonal levels. Muscle soreness and countermovement jump were quantified daily. The physical performance comparisons did not present differences and the only between group comparison with a large effect size (ES = -1.39) was in Δ% between day 1 and day 2 for countermovement jump. Delayed onset muscle soreness and creatine kinase increased in both groups and the ESs of between group comparisons of Δ% between moments were not more than moderate. Thigh circumference increased only in the placebo group (p = 0.04) and the ES of the between group comparisons of Δ% between moments was large (1.53). No differences were found in oxidative stress, or inflammatory markers. Cortisol decreased only in the CWI-group (p ≤ 0.05) and the ESs of the between group comparisons of Δ% between moments of the testosterone to cortisol ratio (-1.94) and insulin-like growth-1 (-1.34) were large. Despite the positive effects of daily CWI on muscle edema and hormonal status, the limited effects of CWI on performance, muscle damage, inflammation markers, and reactive oxygen species mediators signal the unimportance of the daily practice of this recovery method in volleyball players.

Dietary Creatine Supplementation in Gilthead Seabream (Sparus aurata): Comparative Proteomics Analysis on Fish Allergens, Muscle Quality, and Liver.

The quality of fish flesh depends on the skeletal muscle's energetic state and delaying energy depletion through diets supplementation could contribute to the preservation of muscle's quality traits and modulation of fish allergens. Food allergies represent a serious public health problem worldwide with fish being one of the top eight more allergenic foods. Parvalbumins, have been identified as the main fish allergen. In this study, we attempted to produce a low allergenic farmed fish with improved muscle quality in controlled artificial conditions by supplementing a commercial fish diet with different creatine percentages. The supplementation of fish diets with specific nutrients, aimed at reducing the expression of parvalbumin, can be considered of higher interest and beneficial in terms of food safety and human health. The effects of these supplemented diets on fish growth, physiological stress, fish muscle status, and parvalbumin modulation were investigated. Data from zootechnical parameters were used to evaluate fish growth, food conversion ratios and hepatosomatic index. Physiological stress responses were assessed by measuring cortisol releases and muscle quality analyzed by rigor mortis and pH. Parvalbumin, creatine, and glycogen concentrations in muscle were also determined. Comparative proteomics was used to look into changes in muscle and liver tissues at protein level. Our results suggest that the supplementation of commercial fish diets with creatine does not affect farmed fish productivity parameters, or either muscle quality. Additionally, the effect of higher concentrations of creatine supplementation revealed a minor influence in fish physiological welfare. Differences at the proteome level were detected among fish fed with different diets. Differential muscle proteins expression was identified as tropomyosins, beta enolase, and creatine kinase among others, whether in liver several proteins involved in the immune system, cellular processes, stress, and inflammation response were modulated. Regarding parvalbumin modulation, the tested creatine percentages added to the commercial diet had also no effect in the expression of this protein. The use of proteomics tools showed to be sensitive to infer about changes of the underlying molecular mechanisms regarding fish responses to external stimulus, providing a holistic and unbiased view on fish allergens and muscle quality.

PSIII-35 Dietary glycine+serine and threonine effects on performance, creatine muscle content and meat lipid oxidation of broiler chickens from 21 to 42 days of age.

PSIII-35 Dietary glycine+serine and threonine effects on performance, creatine muscle content and meat lipid oxidation of broiler chickens from 21 to 42 days of age.

A Performance Evaluation of Liver and Skeletal Muscle-Specific miRNAs in Rat Plasma to Detect Drug-Induced Injury.

Liver and skeletal muscle-specific microRNAs (miRNAs) are currently being evaluated as novel plasma biomarkers that may out-perform or add value to the conventional liver injury biomarkers alanine aminotransferase (ALT) and aspartate aminotransferase (AST), and to the skeletal muscle injury biomarkers AST and creatine kinase (CK). A comprehensive evaluation was conducted to assess the relative performance of these miRNAs to detect and distinguish liver from muscle tissue injury. The performance of miR-122 and miR-192 for liver and miR-1, miR-133a, miR-133b, and miR-206 for skeletal muscle was compared with 10 enzymatic or protein biomarkers across 27 compounds causing specific types of tissue injury in rat. Receiver operator characteristic analyses were performed comparing the relative sensitivity and specificity of each of the biomarkers in individual animals with histopathology observations of necrosis and/or degeneration in various organs. All of the miRNAs outperformed ALT, AST, and/or CK in studies with either liver or skeletal muscle injury and demonstrated superior specificity in organs without type-specific injury (eg, liver biomarkers assessed with compounds that cause skeletal muscle injury). When additional protein biomarkers were included, glutamate dehydrogenase, arginase I, alpha-glutathione S-transferase for liver and skeletal troponin I, myosin light chain 3, fatty acid-binding protein 3, and creatine kinase M isoform for skeletal muscle, the miRNAs demonstrated equal or superior performance to the extended panel. Taken together, this comprehensive evaluation demonstrates that these novel miRNA toxicity biomarkers outperform and add value with respect to sensitivity and specificity over ALT, AST in monitoring the liver and over CK for monitoring skeletal muscle drug-induced injury.

Mutant myocilin impacts sarcomere ultrastructure in mouse gastrocnemius muscle.

Myocilin (MYOC) is the gene with mutations most common in glaucoma. In the eye, MYOC is in trabecular meshwork, ciliary body, and retina. Other tissues with high MYOC transcript levels are skeletal muscle and heart. To date, the function of wild-type MYOC remains unknown and how mutant MYOC causes high intraocular pressure and glaucoma is ambiguous. By investigating mutant MYOC in a non-ocular tissue we hoped to obtain novel insight into mutant MYOC pathology. For this study, we utilized a transgenic mouse expressing human mutant MYOC Y437H protein and we examined its skeletal (gastrocnemius) muscle phenotype. Electron micrographs showed that sarcomeres in the skeletal muscle of mutant CMV-MYOC-Y437H mice had multiple M-bands. Western blots of soluble muscle lysates from transgenics indicated a decrease in two M-band proteins, myomesin 1 (MYOM1) and muscle creatine kinase (CKM). Immunoprecipitation identified CKM as a MYOC binding partner. Our results suggest that binding of mutant MYOC to CKM is changing sarcomere ultrastructure and this may adversely impact muscle function. We speculate that a person carrying the mutant MYOC mutation will likely have a glaucoma phenotype and may also have undiagnosed muscle ailments or vice versa, both of which will have to be monitored and treated.

Role of the α2 subunit of AMP-activated protein kinase and its nuclear localization in mitochondria and energy metabolism-related gene expressions in C2C12 cells

BackgroundAMP-activated protein kinase (AMPK), a heterotrimer with α1 or α2 catalytic subunits, acts as an energy sensor and regulates cellular homeostasis. Whereas AMPKα1 is necessary for myogenesis in skeletal muscle, the role of AMPKα2 in myogenic differentiation and energy metabolism-related gene expressions has remained unclear. We here examined the specific roles of AMPKα1 and AMPKα2 in the myogenic differentiation and mitochondria and energy metabolism-related gene expressions in C2C12 cells. Materials and MethodsStable C2C12 cell lines expressing a scramble short hairpin RNA (shRNA) or shRNAs specific for AMPKα1 (shAMPKα1), AMPKα2 (shAMPKα2), or both AMPKα1 and AMPKα2 (shPanAMPK) were generated by lentivirus infection. Lentiviruses encoding wild-type AMPKα2 (WT-AMPKα2) or AMPKα2 with a mutated nuclear localization signal (ΔNLS-AMPKα2) were also constructed for introduction into myoblasts. Myogenesis was induced by culture of C2C12 myoblasts for 6 days in differentiation medium. ResultsThe amount of AMPKα2 increased progressively, whereas that of AMPKα1 remained constant, during the differentiation of myoblasts into myotubes. Expression of shPanAMPK or shAMPKα1, but not that of shAMPKα2, attenuated the proliferation of myoblasts as well as the phosphorylation of both acetyl-CoA carboxylase and the autophagy-initiating kinase ULK1 in myotubes. Up-regulation of myogenin mRNA, a marker for the middle stage of myogenesis, was attenuated in differentiating myotubes expressing shPanAMPK or shAMPKα1. In contrast, up-regulation of gene expression for muscle creatine kinase (MCK), a late-stage differentiation marker, as well as for genes related to mitochondrial biogenesis including the transcriptional coactivator peroxisome proliferator–activated receptor–γ coactivator–1α1 and α4 (PGC-1α1 and PGC-1α4) and mitochondria-specific genes such as cytochrome c were attenuated in myotubes expressing shAMPKα2 or shPanAMPK. The diameter of myotubes expressing shPanAMPK or shAMPKα2 was reduced, whereas that of those expressing shAMPKα1 was increased, compared with myotubes expressing scramble shRNA. A portion of AMPKα2 became localized to the nucleus during myogenic differentiation. The AMPK activator AICAR (5-aminoimidazole-4-carboxamide ribonucleotide) and 2-deoxyglucose (2DG) each induced the nuclear translocation of WT-AMPKα2, but not that of ΔNLS-AMPKα2. Finally, expression of WT-AMPKα2 increased the mRNA abundance of PGC-1α1 and MCK mRNAs as well as cell diameter and tended to increase that of PGC-1α4, whereas that of ΔNLS-AMPKα2 increased only the abundance of MCK mRNA, in myotubes depleted of endogenous AMPKα2. ConclusionTAMPKα1 and AMPKα2 have distinct roles in myogenic differentiation of C2C12 cells, with AMPKα1 contributing to the middle stage of myogenesis and AMPKα2 to the late stage. AMPKα2 regulates gene expressions including MCK, PGC-1α1 and PGC-1α4 and mitochondria-specific genes such as cytochrome c during the late stage of differentiation. Furthermore, the nuclear translocation of AMPKα2 is necessary for maintenance of PGC-1α1 mRNA during myogenesis.

DREADD technology reveals major impact of Gq signalling on cardiac electrophysiology

Signalling via Gq-coupled receptors is of profound importance in many cardiac diseases such as hypertrophy and arrhythmia. Nevertheless, owing to their widespread expression and the inability to selectively stimulate such receptors in vivo, their relevance for cardiac function is not well understood. We here use DREADD technology to understand the role of Gq-coupled signalling in vivo in cardiac function. We generated a novel transgenic mouse line that expresses a Gq-coupled DREADD (Dq) in striated muscle under the control of the muscle creatine kinase promotor. In vivo injection of the DREADD agonist clozapine-N-oxide (CNO) resulted in a dose-dependent, rapid mortality of the animals. In vivo electrocardiogram data revealed severe cardiac arrhythmias including lack of P waves, atrioventricular block, and ventricular tachycardia. Following Dq activation, electrophysiological malfunction of the heart could be recapitulated in the isolated heart ex vivo. Individual ventricular and atrial myocytes displayed a positive inotropic response and arrhythmogenic events in the absence of altered action potentials. Ventricular tissue sections revealed a strong co-localization of Dq with the principal cardiac connexin CX43. Western blot analysis with phosphor-specific antibodies revealed strong phosphorylation of a PKC-dependent CX43 phosphorylation site following CNO application in vivo. Activation of Gq-coupled signalling has a major impact on impulse generation, impulse propagation, and coordinated impulse delivery in the heart. Thus, Gq-coupled signalling does not only modulate the myocytes' Ca2+ handling but also directly alters the heart's electrophysiological properties such as intercellular communication. This study greatly advances our understanding of the plethora of modulatory influences of Gq signalling on the heart in vivo.

Long noncoding RNA SYISL regulates myogenesis by interacting with polycomb repressive complex 2

Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their physiological function and regulatory mechanisms remain largely unexplored. In this study, we systematically characterized the expression profiles of lncRNAs during C2C12 myoblast differentiation and identified an intronic lncRNA, SYISL (SYNPO2 intron sense-overlapping lncRNA), that is highly expressed in muscle. Functionally, SYISL promotes myoblast proliferation and fusion but inhibits myogenic differentiation. SYISL knockout in mice results in significantly increased muscle fiber density and muscle mass. Mechanistically, SYISL recruits the enhancer of zeste homolog 2 (EZH2) protein, the core component of polycomb repressive complex 2 (PRC2), to the promoters of the cell-cycle inhibitor gene p21 and muscle-specific genes such as myogenin (MyoG), muscle creatine kinase (MCK), and myosin heavy chain 4 (Myh4), leading to H3K27 trimethylation and epigenetic silencing of target genes. Taken together, our results reveal that SYISL is a repressor of muscle development and plays a vital role in PRC2-mediated myogenesis.

Rhabdomyolysis as a rare but fatal complication of bariatric surgery: A case report.

Rhabdomyolysis after bariatric surgery is a quite rare occurrence with low recognition. Due to the breakdown of the striated muscle fibers, creatine kinase and myoglobin are released into the systemic circulation with variable effects on the renal filtration functions. Herein we present the case of a patient who developed rhabdomyolysis following revision bariatric surgery. A 34-year-old male patient was admitted for bariatric surgery. He had undergone a gastric band surgery approximately 6 years ago, with weight regain starting 1 year postoperatively gradually reaching the previous weight level. Consequently, the gastric band was removed with open surgery 3 years ago. The patient had a body mass index of 69 kg/m2 and an incisional hernia due to the previous surgery. Although initially, laparoscopic sleeve gastrectomy was planned, a switch to open surgery was made due to the presence of diffuse intra-abdominal adhesions and a giant incisional hernia precluding a laparoscopic intervention. The total duration of surgery was 420 min. Postoperative laboratory work-up showed elevated blood creatine kinase levels (25837 U/L). Upon the failure of fluid replacement and diuretics, hemodialysis was initiated on postoperative day 1. Despite daily sessions of hemodialysis, the patient's acidosis did not improve; his general status worsened, and he died on postoperative day 14. Rhabdomyolysis is a severe and potentially life-threatening complication of bariatric surgery. Its severity may vary from asymptomatic elevation in creatine kinase levels to death. Postoperative creatine kinase levels should be routinely monitored in high-risk patients as a practical and inexpensive laboratory modality for early diagnosis.

Randomized controlled trial examining the effect of creatine and maltodextrin on functional level in stroke rehabilitation

Rationale: Stroke patients may suffer from palsy, which leads to an increased energy expenditure when moving the paretic limb. Stroke patients experience fatigue at a low level of physical activity. Fatigue is associated with reduced glycogen storage and thereby a decreased production of adenosine triphosphate (ATP). Muscle glycogen and creatine phosphate are the major substrates.

A novel direct link between Ca2+ signalling and energy homeostasis? Structural background of brain and muscle creatine kinase modulation by calmodulin

A novel direct link between Ca²⁺ signalling and energy homeostasis? Structural background of brain and muscle creatine kinase modulation by calmodulin

Bone-Targeted Alkaline Phosphatase Treatment of Mandibular Bone and Teeth in Lethal Hypophosphatasia via an scAAV8 Vector

Hypophosphatasia is an inherited disease caused by mutations in the gene encoding tissue-nonspecific alkaline phosphatase (TNALP), the major symptom of which is hypomineralization of the bones and teeth. We had recently demonstrated that TNALP-deficient (Akp2−/−) mice, which mimic the phenotype of the severe infantile form of hypophosphatasia, can be treated by intramuscular injection of a self-complementary (sc) type 8 recombinant adeno-associated virus (rAAV8) vector expressing bone-targeted TNALP with deca-aspartates at the C terminus (TNALP-D10) via the muscle creatine kinase (MCK) promoter. In this study, we focused on the efficacy of this scAAV8-MCK-TNALP-D10 treatment on the mandibular bone and teeth in neonatal Akp2−/− mice. Upon scAAV8-MCK-TNALP-D10 injection, an improvement of mandibular growth was observed by X-ray analysis. Micro-computed tomography analysis revealed progressive mineralization of the molar root in the treated Akp2−/− mice, and morphometric parameters of the alveolar bone were improved. These results suggest that the mandibular bones and teeth of hypophosphatasia were effectively treated by muscle directed rAAV-mediated TNALP-D10 transduction. Our strategy would be promising for future hypophosphatasia gene therapy because it induces dentoalveolar mineralization and reduces the risk of tooth exfoliation.

Beyond muscle: the effects of creatine supplementation on brain creatine, cognitive processing, and traumatic brain injury

The ergogenic and therapeutic effects of increasing muscle creatine by supplementation are well-recognized. It appears that similar benefits to brain function and cognitive processing may also be achieved with creatine supplementation, however research in this area is more limited, and important knowledge gaps remain. The purpose of this review is to provide a comprehensive overview of the current state of knowledge about the influence of creatine supplementation on brain function in healthy individuals. It appears that brain creatine is responsive to supplementation, however higher, or more prolonged dosing strategies than those typically used to increase muscle creatine, may be required to elicit an increase in brain creatine. The optimal dosing strategy to induce this response, is currently unknown, and there is an urgent need for studies investigating this. When considering the influence of supplementation strategies on cognitive processes, it appears that creatine is most likely to exert an influence in situations whereby cognitive processes are stressed, e.g. during sleep deprivation, experimental hypoxia, or during the performance of more complex, and thus more cognitively demanding tasks. Evidence exists indicating that increased brain creatine may be effective at reducing the severity of, or enhancing recovery from mild traumatic brain injury, however, only limited data in humans are available to verify this hypothesis, thus representing an exciting area for further research.

A Mouse Model of Creatine Transporter Deficiency Reveals Impaired Motor Function and Muscle Energy Metabolism.

Creatine serves as fast energy buffer in organs of high-energy demand such as brain and skeletal muscle. L-Arginine:glycine amidinotransferase (AGAT) and guanidinoacetate N-methyltransferase are responsible for endogenous creatine synthesis. Subsequent uptake into target organs like skeletal muscle, heart and brain is mediated by the creatine transporter (CT1, SLC6A8). Creatine deficiency syndromes are caused by defects of endogenous creatine synthesis or transport and are mainly characterized by intellectual disability, behavioral abnormalities, poorly developed muscle mass, and in some cases also muscle weakness. CT1-deficiency is estimated to be among the most common causes of X-linked intellectual disability and therefore the brain phenotype was the main focus of recent research. Unfortunately, very limited data concerning muscle creatine levels and functions are available from patients with CT1 deficiency. Furthermore, different CT1-deficient mouse models yielded conflicting results and detailed analyses of their muscular phenotype are lacking. Here, we report the generation of a novel CT1-deficient mouse model and characterized the effects of creatine depletion in skeletal muscle. HPLC-analysis showed strongly reduced total creatine levels in skeletal muscle and heart. MR-spectroscopy revealed an almost complete absence of phosphocreatine in skeletal muscle. Increased AGAT expression in skeletal muscle was not sufficient to compensate for insufficient creatine transport. CT1-deficient mice displayed profound impairment of skeletal muscle function and morphology (i.e., reduced strength, reduced endurance, and muscle atrophy). Furthermore, severely altered energy homeostasis was evident on magnetic resonance spectroscopy. Strongly reduced phosphocreatine resulted in decreased ATP/Pi levels despite an increased inorganic phosphate to ATP flux. Concerning glucose metabolism, we show increased glucose transporter type 4 expression in muscle and improved glucose clearance in CT1-deficient mice. These metabolic changes were associated with activation of AMP-activated protein kinase – a central regulator of energy homeostasis. In summary, creatine transporter deficiency resulted in a severe muscle weakness and atrophy despite different compensatory mechanisms.