Estrogen deficiency reduces maximal running capacity and affects serotonin levels differently in the hippocampus and nucleus accumbens in response to acute exercise.

Introduction: Estrogen deficiency is associated with unfavorable changes in body composition and metabolic health. While physical activity ameliorates several of the negative effects, loss of ovarian function is associated with decreased physical activity levels. It has been proposed that the changes in brain neurochemical levels and /or impaired skeletal muscle function may underlie this phenomenon. Methods: We studied the effect of estrogen deficiency induced via ovariectomy (OVX) in female Wistar rats (n = 64). Rats underwent either sham or OVX surgery and were allocated thereafter into four groups matched for body mass and maximal running capacity: sham/control, sham/max, OVX/control, and OVX/max, of which the max groups had maximal running test before euthanasia to induce acute response to exercise. Metabolism, spontaneous activity, and maximal running capacity were measured before (PRE) and after (POST) the surgeries. Three months following the surgery, rats were euthanized, and blood and tissue samples harvested. Proteins were analyzed from gastrocnemius muscle and retroperitoneal adipose tissue via Western blot. Brain neurochemical markers were measured from nucleus accumbens (NA) and hippocampus (HC) using ultra-high performance liquid chromatography. Results: OVX had lower basal energy expenditure and higher body mass and retroperitoneal adipose tissue mass compared with sham group (p ≤ 0.005). OVX reduced maximal running capacity by 17% (p = 0.005) with no changes in muscle mass or phosphorylated form of regulatory light chain (pRLC) in gastrocnemius muscle. OVX was associated with lower serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) level in the NA compared with sham (p = 0.007). In response to acute exercise, OVX was associated with low serotonin level in the HC and high level in the NA (p ≤ 0.024). Discussion: Our results highlight that OVX reduces maximal running capacity and affects the response of brain neurochemical levels to acute exercise in a brain region-specific manner. These results may offer mechanistic insight into why OVX reduces willingness to exercise.

Skeletal muscle dysfunction with advancing age.

As a result of advances in medical treatments and associated policy over the last century, life expectancy has risen substantially and continues to increase globally. However, the disconnect between lifespan and 'health span' (the length of time spent in a healthy, disease-free state) has also increased, with skeletal muscle being a substantial contributor to this. Biological ageing is accompanied by declines in both skeletal muscle mass and function, termed sarcopenia. The mechanisms underpinning sarcopenia are multifactorial and are known to include marked alterations in muscle protein turnover and adaptations to the neural input to muscle. However, to date, the relative contribution of each factor remains largely unexplored. Specifically, muscle protein synthetic responses to key anabolic stimuli are blunted with advancing age, whilst alterations to neural components, spanning from the motor cortex and motoneuron excitability to the neuromuscular junction, may explain the greater magnitude of function losses when compared with mass. The consequences of these losses can be devastating for individuals, their support networks, and healthcare services; with clear detrimental impacts on both clinical (e.g., mortality, frailty, and post-treatment complications) and societal (e.g., independence maintenance) outcomes. Whether declines in muscle quantity and quality are an inevitable component of ageing remains to be completely understood. Nevertheless, strategies to mitigate these declines are of vital importance to improve the health span of older adults. This review aims to provide an overview of the declines in skeletal muscle mass and function with advancing age, describes the wide-ranging implications of these declines, and finally suggests strategies to mitigate them, including the merits of emerging pharmaceutical agents.

Skeletal muscle mass and kidney function among Chinese older adults: a cross-sectional study.

OBJECTIVES: To assess the association between kidney function and odds of having low skeletal muscle mass (LSMM) in Chinese adults on the basis of a community study. DATA AND METHODS: In this cross-sectional study, we included 3726 Chinese older persons who participated in an ongoing prospective study, the China Health and Retirement Longitudinal Study(CHARLS). Fasting blood samples were collected in 2012 and analyzed for serum creatinine. Estimated glomerular filtration rate(eGFR) was computed using serum creatinine, gender, and age, according to the 2021 race-free Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI). We classified the target population into three categories according to eGFR (normal eGFR;90mL/min/1.73m2, mildly-impaired eGFR;60 to < 90 mL/min/1.73 m2, moderate to severve impaired eGFR;<60 mL/min/1.73 m2). BMI-adjusted muscle mass was used to measure skeletal muscle mass.The association between eGFR(per interquartile range(IQR) increment) and the risk of low skeletal muscle mass was assessed using logistic regression model. RESULTS: Worsening renal function was associated with being high risk for LSMM after adjusting for potential confounders:the odds ratios (ORs) 95% confidence intervals (CIs) were 0.76 (95% CI = 0.63 - 0.88) for male, and [0.71, (0.61-0.82)]in female, p < 0.001. Specifically, male participants with mildly renal impairment were more prone to develop LSMM (multiadjusted OR, 1.43, 95% CI(0.92 to 2.09), p = 0.1) than femal(multiadjusted OR, 1.32, 95% CI(0.85 to 2.00), p = 0.2), the gender difference was not significant in severe renal dysfunction.However, there was a non-linear relationship between eGFR(per IQR increment) and risk of LSMM(eGFR/IQR =5.42, knot = 4 OR =1, p for non-linear <0.001). CONCLUSIONS: Lower levels of eGFR had a high likelihood of being high risk for LSMM. Older male patients with mildly renal insufficiency are more likely to experience a decrease in skeletal muscle mass compared to female.

Deletion of miPEP in adipocytes protects against obesity and insulin resistance by boosting muscle metabolism.

Mitochondria facilitate thousands of biochemical reactions, covering a broad spectrum of anabolic and catabolic processes. Here we demonstrate that the adipocyte mitochondrial proteome is markedly altered across multiple models of insulin resistance and reveal a consistent decrease in the level of the mitochondrial processing peptidase miPEP. OBJECTIVE: To determine the role of miPEP in insulin resistance. METHODS: To experimentally test this observation, we generated adipocyte-specific miPEP knockout mice to interrogate its role in the aetiology of insulin resistance. RESULTS: We observed a strong phenotype characterised by enhanced insulin sensitivity and reduced adiposity, despite normal food intake and physical activity. Strikingly, these phenotypes vanished when mice were housed at thermoneutrality, suggesting that metabolic protection conferred by miPEP deletion hinges upon a thermoregulatory process. Tissue specific analysis of miPEP deficient mice revealed an increment in muscle metabolism, and upregulation of the protein FBP2 that is involved in ATP hydrolysis in the gluconeogenic pathway. CONCLUSION: These findings suggest that miPEP deletion initiates a compensatory increase in skeletal muscle metabolism acting as a protective mechanism against diet-induced obesity and insulin resistance.

Six weeks of localized passive heat therapy elicits some exercise-like improvements in resistance artery function.

The purpose of this study was to examine the effects of 6 weeks of localized, muscle-focused (quadriceps femoris) passive heat therapy (PHT) on resistance artery function, exercise haemodynamics and exercise performance relative to knee extension (KE) exercise training (EX). We randomized 34 healthy adults (ages 18-36; n = 17 female, 17 male) to receive either PHT or sham heating sessions (120 min, 3 days/week), or EX (40 min, 3 days/week) over 6 weeks. Blood flow was assessed with Doppler ultrasound of the femoral artery during both passive leg movement (PLM) and a KE graded exercise test. Muscle biopsies were taken from the vastus lateralis at baseline and after 6 weeks. Peak blood flow during PLM increased to the same extent in both the EX (∼10.5% increase, P = 0.009) and PHT groups (∼8.5% increase, P = 0.044). Peak flow during knee extension exercise increased in EX (∼19%, P = 0.005), but did not change in PHT (P = 0.523) and decreased in SHAM (∼7%, P = 0.020). Peak vascular conductance during KE increased by ∼25% in EX (P = 0.030) and PHT (P = 0.012). KE peak power increased in EX by ∼27% (P = 0.001) but did not significantly change in PHT and SHAM groups. Expression of endothelial nitric oxide synthase increased significantly in both EX (P = 0.028) and PHT (P = 0.0095), but only EX resulted in increased angiogenesis. In conclusion, 6 weeks of localized PHT improved resistance artery function at rest and during exercise to the same extent as exercise training but did not yield significant improvements in performance. KEY POINTS: Many for whom exercise would be most beneficial are either unable to exercise or have a very low exercise tolerance. In these cases, an alternative treatment to combat declines in resistance artery function is needed. We tested the hypothesis that passive heat therapy (PHT) would increase resistance artery function, improve exercise haemodynamics and enhance exercise performance compared to a sham treatment, but less than aerobic exercise training. This report shows that 6 weeks of localized PHT improved resistance artery function at rest and during exercise to the same extent as exercise training but did not improve exercise performance. Additionally, muscle biopsy analyses revealed that endothelial nitric oxide synthase expression increased in both PHT and exercise training groups, but only exercise resulted in increased angiogenesis. Our data demonstrate the efficacy of applying passive heat as an alternative treatment to improve resistance artery function for those unable to receive the benefits of regular exercise.

Relative rDNA copy number is not associated with resistance training-induced skeletal muscle hypertrophy and does not affect myotube anabolism in vitro.

Ribosomal DNA (rDNA) copies exist across multiple chromosomes and inter-individual variation in copy number is speculated to influence the hypertrophic response to resistance training. Thus, we examined if rDNA copy number was associated with resistance training-induced skeletal muscle hypertrophy. Participants (n=53 males, 21±1 years old; n=29 females, 21±2 years old) performed 10-12 weeks of full-body resistance training. Hypertrophy outcomes were determined, as was relative rDNA copy number from pre-intervention vastus lateralis (VL) biopsies. Pre- and post-intervention VL biopsy total RNA was assayed in all participants, and mRNA/rRNA markers of ribosome content and biogenesis were also assayed in the 29 females prior to training, 24 hours following training bout 1, and in the basal state after 10 weeks of training. Across all participants, no significant associations were evident between relative rDNA copy number and training-induced changes in whole body lean mass (r = -0.034, p=0.764), vastus lateralis thickness (r = 0.093, p=0.408), mean myofiber cross-sectional area (r = -0.128, p=0.259), or changes in muscle RNA concentrations (r = 0.026, p=0.818), and these trends were similar when examining each gender. However, all Pol-I regulon mRNAs as well as 45S pre-rRNA, 28S rRNA and 18S rRNA increased 24 hours following the first training bout in females. Follow-up studies using LHCN-M2 myotubes demonstrated a reduction in relative rDNA copy number induced by bisphenol A (BPA) did not significantly affect insulin-like-growth factor-induced myotube hypertrophy. These findings suggest relative rDNA copy number is not associated with myofiber hypertrophy.

Relationship between physical functional status indicators and bone mineral density in older women.

Background: Osteoporosis significantly predisposes patients to fragility fractures and a reduced quality of life. Therefore, osteoporosis prevention plays an important role in extending healthy life expectancy. The purpose of this study was to identify whether physical functional status was associated with low bone mineral density, and to determine cut-off values of physical status indicators for osteoporosis. Methods: This cross-sectional study evaluated 343 women aged 60 years or older who were able to walk independently. The measured variables were the body mass index, lumbar and total hip bone mineral density, grip strength, 5-m normal walking speed, one-leg standing time, timed up-and-go test, and skeletal muscle mass using bioelectrical impedance analysis. The associations between physical status indicators and low bone mineral density were analyzed and the cut-off values for detecting osteoporosis were calculated using receiver operating characteristic curve analyses. Results: The prevalence of osteoporosis was 29.2 %. All measured variables significantly differed between the osteoporotic and non-osteoporotic groups (p < 0.05). Multivariate logistic regression analysis showed that the factors associated with osteoporosis were the skeletal muscle mass index, walking speed, and body mass index. In the receiver operating characteristic curve analysis, the cut-off values of the skeletal muscle mass index, walking speed, and body mass index associated with osteoporosis were 6.31 kg/m2, 1.29 m/s, and 22.6 kg/m2, respectively. Conclusions: Older women with low bone mineral density have lower skeletal muscle mass, slower walking speed, and lower body mass index. Measuring the skeletal muscle mass index, walking speed, and body mass index might be useful for daily exercise guidance or osteoporosis screening.

Data describing the effects of Induced knockout of Heterogeneous nuclear ribonucleoprotein K in mouse skeletal muscle satellite cells.

HnRNPK, a prominent member of the heterogeneous nuclear ribonucleoprotein (hnRNP) family, is widely expressed in mammalian tissues and plays a crucial role in animal development. Despite its well-established functions, limited information is available regarding its role in skeletal muscle development and regeneration. To elucidate the functional role of hnRNPK in skeletal muscle, we utilized Pax7CreER; HnrnpkLoxP/LoxP (Hnrnpk pKO) mice as a model, isolated primary mouse skeletal muscle satellite cells (MuSCs), and induced hnRNPK knockout using 4-OTH. Transcriptome sequencing was performed on four distinct groups: Hnrnpk pKO MuSCs undergoing proliferation for 24 h (ethanol 24 h) and 48 h (ethanol 48 h) after treatment with ethanol as the control, as well as Hnrnpk pKO MuSCs undergoing proliferation for 24 h (4-OHT 24 h) and 48 h (4-OHT 48 h) after treatment with 4-OHT as the hnRNPK-induced knockout group. The RNA sequencing data was generated using the Illumina HiSeq 2000/2500 sequencing platform. The raw data files have been archived in the Sequence Read Archive at the China National Center for Bioinformation (CNCB) under the accession number CRA015864. This data article is related to the research paper "Deletion of heterogeneous nuclear ribonucleoprotein K in satellite cells leads to inhibited skeletal muscle regeneration in mice, Genes & Diseases 11: 101,062, DOI: 10.1016/j.gendis.2023.06.031".

Mitochondrial bioenergetics are not associated with myofibrillar protein synthesis rates.

BACKGROUND: Mitochondria represent key organelles influencing cellular homeostasis and have been implicated in the signalling events regulating protein synthesis. METHODS: We examined whether mitochondrial bioenergetics (oxidative phosphorylation and reactive oxygen species (H2O2) emission, ROS) measured in vitro in permeabilized muscle fibres represent regulatory factors for integrated daily muscle protein synthesis rates and skeletal muscle mass changes across the spectrum of physical activity, including free-living and bed-rest conditions: n = 19 healthy, young men (26 ± 4 years, 23.4 ± 3.3 kg/m2) and following 12 weeks of resistance-type exercise training: n = 10 healthy older men (70 ± 3 years, 25.2 ± 2.1 kg/m2). Additionally, we evaluated the direct relationship between attenuated mitochondrial ROS emission and integrated daily myofibrillar and sarcoplasmic protein synthesis rates in genetically modified mice (mitochondrial-targeted catalase, MCAT). RESULTS: Neither oxidative phosphorylation nor H2O2 emission were associated with muscle protein synthesis rates in healthy young men under free-living conditions or following 1 week of bed rest (both P > 0.05). Greater increases in GSSG concentration were associated with greater skeletal muscle mass loss following bed rest (r = -0.49, P < 0.05). In older men, only submaximal mitochondrial oxidative phosphorylation (corrected for mitochondrial content) was positively associated with myofibrillar protein synthesis rates during exercise training (r = 0.72, P < 0.05). However, changes in oxidative phosphorylation and H2O2 emission were not associated with changes in skeletal muscle mass following training (both P > 0.05). Additionally, MCAT mice displayed no differences in myofibrillar (2.62 ± 0.22 vs. 2.75 ± 0.15%/day) and sarcoplasmic (3.68 ± 0.35 vs. 3.54 ± 0.35%/day) protein synthesis rates when compared with wild-type mice (both P > 0.05). CONCLUSIONS: Mitochondrial oxidative phosphorylation and reactive oxygen emission do not seem to represent key factors regulating muscle protein synthesis or muscle mass regulation across the spectrum of physical activity.

Key considerations for investigating and interpreting autophagy in skeletal muscle.

Skeletal muscle plays a crucial role in generating force to facilitate movement. Skeletal muscle is a heterogenous tissue composed of diverse fibers with distinct contractile and metabolic profiles. The intricate classification of skeletal muscle fibers exists on a continuum ranging from type I (slow-twitch, oxidative) to type II (fast-twitch, glycolytic). The heterogenous distribution and characteristics of fibers within and between skeletal muscles profoundly influences cellular signaling; however, this has not been broadly discussed as it relates to macroautophagy/autophagy. The growing interest in skeletal muscle autophagy research underscores the necessity of comprehending the interplay between autophagic responses among skeletal muscles and fibers with different contractile properties, metabolic profiles, and other related signaling processes. We recommend approaching the interpretation of autophagy findings with careful consideration for two key reasons: 1) the distinct behaviors and responses of different skeletal muscles or fibers to various perturbations, and 2) the potential impact of alterations in skeletal muscle fiber type or metabolic profile on observed autophagic outcomes. This review provides an overview of the autophagic profile and response in skeletal muscles/fibers of different types and metabolic profiles. Further, this review discusses autophagic findings in various conditions and diseases that may differentially affect skeletal muscle. Finally, we provide key points of consideration to better enable researchers to fine-tune the design and interpretation of skeletal muscle autophagy experiments.Abbreviation: AKT1: AKT serine/threonine kinase 1; AMPK: AMP-activated protein kinase; ATG: autophagy related; ATG4: autophagy related 4 cysteine peptidase; ATG5: autophagy related 5; ATG7: autophagy related 7; ATG12: autophagy related 12; BECN1: beclin 1; BNIP3: BCL2 interacting protein 3; CKD: chronic kidney disease; COPD: chronic obstructive pulmonary disease; CS: citrate synthase; DIA: diaphragm; EDL: extensor digitorum longus; FOXO3/FOXO3A: forkhead box O3; GAS; gastrocnemius; GP: gastrocnemius-plantaris complex; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK: mitogen-activated protein kinase; MYH: myosin heavy chain; PINK1: PTEN induced kinase 1; PLANT: plantaris; PRKN: parkin RBR E3 ubiquitin protein ligase; QUAD: quadriceps; RA: rectus abdominis; RG: red gastrocnemius; RQ: red quadriceps; SOL: soleus; SQSTM1: sequestosome 1; TA: tibialis anterior; WG: white gastrocnemius; WQ: white quadriceps; WVL: white vastus lateralis; VL: vastus lateralis; ULK1: unc-51 like autophagy activating kinase 1.

Carbohydrate storage in cells: a laboratory activity for the assessment of glycogen stores in biological tissues.

Carbohydrates and fats constitute our primary energy sources. The importance of each of these energy substrates varies across cell types and physiological conditions. For example, the brain normally relies almost exclusively on glucose oxidation, while skeletal muscle shifts from lipids towards higher carbohydrate oxidation rates as exercise intensity increases. Understanding how carbohydrate are stored in our cells and which tissues contain significant carbohydrate stores is crucial for health professionals, especially given the role of carbohydrate metabolism in various pathophysiological conditions. This laboratory activity uses a simple and low-cost iodine binding method to quantify glycogen in mouse skeletal muscle and liver samples. By integrating the results of this activity with literature data, students can determine overall glycogen storage in the human body. The primary goal of the activity is to enhance students understanding of the importance and limitations of glycogen stores in energy metabolism.

Comparative transcriptome analysis of slow-twitch and fast-twitch muscles in Kazakh horses.

This study conducted a thorough analysis of the myofiber type composition in the extensor digitorum longus muscle (EDL) and soleus muscle (SOL) of Kazakh horses, across different genders (male and female). The results showed significant differences in myofiber type composition between EDL and SOL, with a higher proportion of Type I fibers in SOL muscles and a greater prevalence of Type II fibers in EDL muscles. Additionally, the myofiber diameter in Kazakh horses was relatively small, potentially related to the tenderness and edible quality of their muscles. Using high-throughput sequencing technology, we constructed 32 cDNA sequencing libraries and obtained high-quality read data. Gene expression analysis revealed 278 and 372 differentially expressed genes (DEGs) in EDL and SOL muscles, respectively, including genes related to muscle contraction, metabolism, and development. Intersection analysis of DEGs between genders showed that 60 DEGs were significantly different in both male and female horses. GO annotation and KEGG analysis further elucidated the roles of these DEGs in muscle structure, function, and cellular signaling. Protein-protein interaction (PPI) network analysis and identification of hub genes provided new insights into the molecular mechanisms underlying muscle growth and development. Finally, the reliability of the DEGs data was validated through quantitative real-time PCR (qRT-PCR). This study not only enhances our understanding of the biological characteristics of horse muscles but also provides potential molecular targets for improving horse muscle performance and health.

Interpretation of elevated baseline concentrations and serial changes of high-sensitivity cardiac troponin T in confirmed muscular dystrophies.

AIMS: Concentrations of high-sensitivity cardiac troponin T (hs-cTnT) are frequently elevated in stable patients with confirmed muscle dystrophies. However, sparse information is available on the interpretation of serial concentration changes. METHODS: Hs-cTnT was collected in 35 stable outpatients with confirmed skeletal muscle dystrophies at 0 and 1 h and after 6-12 months during scheduled outpatient visits. We simulated the effectiveness of the European Society of Cardiology (ESC) 0/1 h algorithm and assessed biological variation at 6-12 months using two established methods: reference change value (RCV) and minimal important difference (MID). RESULTS: Median baseline hs-cTnT concentrations were 34.4 ng/L [inter-quartile range (IQR): 17.5-46.2], and values > 99th percentile upper limit of normal were present in 34 of 35 patients. All patients were stable without cardiovascular adverse events during a follow-up of 6.6 months (IQR: 6-7). Median concentration change was 1.9 ng/L (IQR: 0.7-3.2) and 0.8 ng/L (IQR: 0-7.0) at 60 min and 6-9 months, respectively. Applying the criteria of the ESC 0/1 h algorithm for triage of suspected acute coronary syndrome (ACS) showed poor overall effectiveness of baseline hs-cTnT values. No patient would qualify for rule-out based on hs-cTnT less than the limit of detection, whereas five cases would qualify for rule-in based on hs-cTnT ≥ 52 ng/L. Biological variabilities at 6-12 months per MID and RCV were 1.2 ng/L [95% confidence interval (CI): 0.7-2.1] and 28.6% (95% CI: 27.9-29.6), respectively. A total of 8 (22.9%) and 25 (71.4%) cases exceeded the biological variation range, suggesting some additional myocardial damage. CONCLUSIONS: The high prevalence of elevated hs-cTnT could negatively impact the effectiveness of rule-out and rule-in strategies based on a single hs-cTnT value. Knowledge of the physiological and biological variation of hs-cTnT after 6-12 months is helpful to detect the progression of cardiac involvement or to search for cardiac complications including but not limited to arrhythmias that may trigger acute or chronic myocardial damage.

Association of Omega-3 Polyunsaturated Fatty Acids with Sarcopenia in Liver Cirrhosis Patients with Hepatocellular Carcinoma.

Background and Aims: Sarcopenia is associated with the prognosis of patients with liver cirrhosis and hepatocellular carcinoma (HCC). Given their diverse physiological activities, we hypothesized that plasma fatty acids might influence the progression of sarcopenia. This study aimed to clarify the association between fatty acids and sarcopenia in cirrhotic patients with HCC. Methods: In this single-center retrospective study, we registered 516 cases and analyzed 414 cases of liver cirrhosis and HCC. The skeletal muscle mass index was measured using a transverse computed tomography scan image at the third lumbar vertebra. The cutoff value for sarcopenia followed the criteria set by the Japan Society of Hepatology. Fatty acid concentrations were measured by gas chromatography. Results: Fatty acid levels, particularly omega-3 (n-3) polyunsaturated fatty acid (PUFA), were lower in patients with poor liver function (Child-Pugh grade B/C) and were negatively correlated with the albumin-bilirubin score (p<0.0001). The prognosis of HCC patients with low PUFA levels was significantly worse. Among the different fatty acid fractions, only n-3 PUFAs significantly correlated with skeletal muscle mass index (p=0.0026). In the multivariate analysis, the n-3 PUFA level was an independent variable associated with sarcopenia (p=0.0006). Conclusions: A low level of n-3 PUFAs was associated with sarcopenia in patients with liver cirrhosis and HCC.

Metastatic Bladder Urothelial Carcinoma Masquerading as Myositis.

Skeletal muscle metastases are uncommon, and metastases of urothelial carcinoma to the skeletal muscle are particularly rare. The most common presentation of skeletal muscle metastases is a focal mass, but their clinical and radiographic findings can be diverse. We present an unusual case of a 71-year-old male without prior known history of malignancy who presented with skeletal muscle pain with imaging most consistent with an inflammatory or infectious process but was ultimately determined to be metastatic urothelial carcinoma from the bladder. This case demonstrates the need to keep an expanded differential for muscular pain, particularly when initial treatments are ineffective.

Myofiber-specific lipidomics unveil differential contributions to insulin sensitivity in individuals of African and European ancestry.

Aims: Individuals of African ancestry (AA) present with lower insulin sensitivity compared to their European counterparts (EA). Studies show ethnic differences in skeletal muscle fiber type (lower type I fibers in AA), muscle fat oxidation capacity (lower in AA), whilst no differences in total skeletal muscle lipids. However, skeletal muscle lipid subtypes have not been examined in this context. We hypothesize that lower insulin sensitivity in AA is due to a greater proportion of type II (non-oxidative) muscle fibers, and that this would result in an ancestry-specific association between muscle lipid subtypes and peripheral insulin sensitivity. To test this hypothesis, we examined the association between insulin sensitivity and muscle lipids in AA and EA adults, and in an animal model of insulin resistance with muscle-specific fiber types. Methods: In this cross-sectional study, muscle biopsies were obtained from individuals with a BMI ranging from normal to overweight with AA (N = 24) and EA (N = 19). Ancestry was assigned via genetic admixture analysis; peripheral insulin sensitivity via hyperinsulinaemic-euglycemic clamp; and myofiber content via myosin heavy chain immunohistochemistry. Further, muscle types with high (soleus) and low (vastus lateralis) type I fiber content were obtained from high-fat diet-induced insulin resistant F1 mice and littermate controls. Insulin sensitivity in mice was assessed via intraperitoneal glucose tolerance test. Mass spectrometry (MS)-based lipidomics was used to measure skeletal muscle lipid. Results: Compared to EA, AA had lower peripheral insulin sensitivity and lower oxidative type 1 myofiber content, with no differences in total skeletal muscle lipid content. Muscles with lower type I fiber content (AA and vastus from mice) showed lower levels of lipids associated with fat oxidation capacity, i.e., cardiolipins, triacylglycerols with low saturation degree and phospholipids, compared to muscles with a higher type 1 fiber content (EA and soleus from mice). Further, we found that muscle diacylglycerol content was inversely associated with insulin sensitivity in EA, who have more type I fiber, whereas no association was found in AA. Similarly, we found that insulin sensitivity in mice was associated with diacylglycerol content in the soleus (high in type I fiber), not in vastus (low in type I fiber).Conclusions; Our data suggest that the lipid contribution to altered insulin sensitivity differs by ethnicity due to myofiber composition, and that this needs to be considered to increase our understanding of underlying mechanisms of altered insulin sensitivity in different ethnic populations.

Skeletal muscle injury treatment using the Silk Elastin® injection in a rat model.

Background: Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury risk. However, effective interventions for SMIs are yet to be established. Hypothesis: The administration of Silk Elastin® (SE), a novel artificial protein, to the SMI site can suppress scar formation and promote tissue repair. Study design: A controlled laboratory study. Methods: In vitro: Fibroblast migration ability was assessed using a scratch assay. SE solution was added to the culture medium, and the fibroblast migration ability was compared across different concentrations. In vivo: An SMI model was established with Sprague-Dawley rats, which were assigned to three groups based on the material injected to the SMI site: SE gel (SE group; n = 8), atelocollagen gel (Atelo group; n = 8), and phosphate buffer saline (PBS group; n = 8). Histological evaluations were performed at weeks 1 and 4 following the SMI induction. In the 1-week model, we detected the expression of transforming growth factor (TGF)-ß1 in the stroma using immunohistological evaluation and real-time polymerase chain reaction analysis. In the 4-week model, we measured tibialis anterior muscle strength upon peroneal nerve stimulation as a functional assessment. Results: In vitro: The fibroblast migration ability was suppressed by SE added at a concentration of 104 µg/mL in the culture medium. In vivo: In the 1-week model, the SE group exhibited significantly lower TGFß -1 expression than the PBS group. In the 4-week model, the SE group had a significantly larger regenerated muscle fiber diameter and smaller scar formation area ratio than the other two groups. Moreover, the SE group was superior to the other two groups in terms of regenerative muscle strength. Conclusion: Injection of SE gel to the SMI site may inhibit tissue scarring by reducing excessive fibroblast migration, thereby enhancing tissue repair. Clinical relevance: The findings of this study may contribute to the development of an early intervention method for SMIs.

Nexus Between Sarcopenia and Microbiome Research: A Bibliometric Exploration.

Despite over 30 years of microbiome and skeletal muscle research, no quantitative analysis of sarcopenia and the microbiome literature had been conducted. Our bibliometric study examined research status, hotspots, and future trends. We utilized bibliometric techniques to search the Science Citation Index Extended Database on February 27, 2023, using the Bibliometrix package in R to create a map displaying scientific production and subject categories. Collaborative network maps between countries/regions were visualized using Scimago Graphica, while VOSviewer explored collaboration modes among individuals and institutions. We analyzed the top 25 emerging keywords, top co-occurring keyword networks, and co-occurring keyword clusters using CiteSpace. A total of 997 articles were retrieved for sarcopenia and microbiome, of which 633 papers were analyzed. Both the number of publications and total citation frequency had been continuously increasing. The United States had the highest total citation frequency, while China had the highest number of publications. Research on the impact of the microbiome on sarcopenia was in its nascent stage and spans multiple disciplines, including nutrition, microbiology, geriatrics, immunology, endocrinology and metabolism, molecular biology, and sports medicine. The University of Copenhagen contributed the most to the number of publications (n=16), with Tibbett M (n=7) and Hulver MW (n=7) among the top authors. The most published journal was "Nutrients" (n=24). Analysis of keywords and clusters revealed new research hotspots in microbes and sarcopenia, such as malnutrition, dietary fiber, signaling pathways, frailty, and intestinal permeability. Research on the impact of the microbiome on sarcopenia is in its infancy and spans multiple disciplines. Malnutrition, dietary fiber, signaling pathways, frailty, and intestinal microbes are currently research hotspots. Furthermore, the visual atlas analysis of research on microbes and sarcopenia helps to track the knowledge structure in research fields related to sarcopenia and microbes, providing direction for future research.

The impact of aerobic exercise timing on BMAL1 protein expression and antioxidant responses in skeletal muscle of mice.

It is well known that the adaptations of muscular antioxidant system to aerobic exercise depend on the frequency, intensity, duration, type of the exercise. Nonetheless, the timing of aerobic exercise, related to circadian rhythms or biological clock, may also affect the antioxidant defense system, but its impact remains uncertain. Bain and muscle ARNT-like 1 (BMAL1) is the core orchestrator of molecular clock, which can maintain cellular redox homeostasis by directly controlling the transcriptional activity of nuclear factor erythroid 2-related factor 2 (NRF2). So, our research objective was to evaluate the impacts of aerobic exercise training at various time points of the day on BMAL1 and NRF2-mediated antioxidant system in skeletal muscle. C57BL/6J mice were assigned to the control group, the group exercising at Zeitgeber Time 12 (ZT12), and the group exercising at ZT24. Control mice were not intervened, while ZT12 and ZT24 mice were trained for four weeks at the early and late time point of their active phase, respectively. We observed that the skeletal muscle of ZT12 mice exhibited higher total antioxidant capacity and lower reactive oxygen species compared to ZT24 mice. Furthermore, ZT12 mice improved the colocalization of BMAL1 with nucleus, the protein expression of BMAL1, NRF2, NAD(P)H quinone oxidoreductase 1, heme oxygenase 1, glutamate-cysteine ligase modifier subunit and glutathione reductase in comparison to those of ZT24 mice. In conclusion, the 4-week aerobic training performed at ZT12 is more effective for enhancing NRF2-mediated antioxidant responses of skeletal muscle, which may be attributed to the specific activation of BMAL1.

Increased prevalence of the null allele of the p.Arg577Ter variant in the ACTN3 gene in Brazilian long-distance athletes: A retrospective study.

INTRODUCTION: The phenotypic consequences of the p.Arg577Ter variant in the α-actinin-3 (ACTN3) gene are suggestive of a trade-off between performance traits for speed and endurance sports. Although there is a consistent association of the c.1729C allele (aka R allele) with strength/power traits, there is still a debate on whether the null allele (c.1729T allele; aka X allele) influences endurance performance. The present study aimed to test the association of the ACTN3 p.Arg577Ter variant with long-distance endurance athlete status, using previously published data with the Brazilian population. METHODS: Genotypic data from 203 long-distance athletes and 1724 controls were analysed in a case-control approach. RESULTS: The frequency of the X allele was significantly higher in long-distance athletes than in the control group (51.5% vs. 41.4%; p = 0.000095). The R/X and X/X genotypes were overrepresented in the athlete group. Individuals with the R/X genotype instead of the R/R genotype had a 1.6 increase in the odds of being a long-distance athlete (p = 0.012), whereas individuals with the X/X genotype instead of the R/R genotype had a 2.2 increase in the odds of being a long-distance athlete (p = 0.00017). CONCLUSION: The X allele, mainly the X/X genotype, was associated with long-distance athlete status in Brazilians.