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Wooden breast (WB) is a myopathy that occurs in pectoralis major (PM) muscles, predominately affecting large, fast-growing broilers. Severe myodegeneration, increased hypoxia, reduced blood flow, and increased collagen deposition are hallmark characteristics of WB that culminate in unsatisfactory fresh meat quality attributes, such as poor water-holding capacity, tenderness, and processing characteristics. Therefore, WB meat is often downgraded resulting in economic losses for the United States poultry industry. Although WB has been well characterized, its etiology remains undefined. As the scientific community continues to resolve mechanisms responsible for WB onset, understanding biochemical changes associated with WB may facilitate solutions to negate its poor meat quality attributes. Given changes in metabolism of living muscle can alter biochemical processes during the conversion of muscle to meat, this review aims to summarize and discuss the current knowledge of WB muscle and meat biochemistry. For example, it appears metabolic pathways that support combating stress are upregulated in WB muscle at the expense of glycolytic flux, which presumably contributes to the high ultimate pH of WB meat. Further, perturbed function of WB mitochondria, such as altered calcium handling, impacts aspects of postmortem metabolism and proteolysis. Collectively, metabolic dysfunction of WB muscle alters the biochemical processes that occur during the conversion of muscle to meat, and thus contributes to the poor WB meat quality. [ABSTRACT FROM AUTHOR]

Sodium Danshensu (SDSS) is extracted from Salvia miltiorrhiza and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4 days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8 weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain (MyHCs) gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the MyHC1 and MyHC2a genes increased while MyHC2b expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited MyH C1 and MyHC2 a expression but promoted MyHC2b expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production. [ABSTRACT FROM AUTHOR]

Background: Low physical performance is associated with higher mortality rate in multiple pathological conditions. Here, we aimed to determine whether body composition and physical performance could be prognostic factors in non‐small cell lung cancer (NSCLC) patients. Moreover, we performed an exploratory approach to determine whether plasma samples from NSCLC patients could directly affect metabolic and structural phenotypes in primary muscle cells. Methods: This prospective cohort study included 55 metastatic NSCLC patients and seven age‐matched control subjects. Assessments included physical performance, body composition, quality of life and overall survival rate. Plasma samples from a sub cohort of 18 patients were collected for exploratory studies in cell culture and metabolomic analysis. Results: We observed a higher survival rate in NSCLC patients with high performance in the timed up‐and‐go (+320%; p =.007), sit‐to‐stand (+256%; p =.01) and six‐minute walking (+323%; p =.002) tests when compared to NSCLC patients with low physical performance. There was no significant association for similar analysis with body composition measurements (p >.05). Primary human myotubes incubated with plasma from NSCLC patients with low physical performance had impaired oxygen consumption rate (−54.2%; p <.0001) and cell proliferation (−44.9%; p =.007). An unbiased metabolomic analysis revealed a list of specific metabolites differentially expressed in the plasma of NSCLC patients with low physical performance. Conclusion: These novel findings indicate that physical performance is a prognostic factor for overall survival in NSCLC patients and provide novel insights into circulating factors that could impair skeletal muscle metabolism. We found that patients with better performance in the timed up‐and‐go, sit‐to‐stand and six‐minutes walking test lived longer in this cohort. Moreover, plasma from NSCLC patients with low physical performance impaired oxygen consumption and extracellular acidification rate and decreased the proliferation of primary human myotubes. Unbiased metabolomics revealed several metabolites differentially expressed in the plasma of NSCLC patients with low physical performance compared to healthy control subjects, with serine and M22G being the most reduced and increased metabolites, respectively. [ABSTRACT FROM AUTHOR]

[Display omitted] The proportion of animal based foods in daily diet of consumers is constantly increasing, with chicken being highly favored due to its high protein and low fat characteristics. The consumption of chicken around the world is steadily increasing. Intramuscular fat (IMF) is a key indicator affecting meat quality. High IMF content can contribute to improve the quality of chicken meat. The regulatory mechanism of IMF deposition in chicken is poorly understood, so its complete elucidation is essential to improve chicken meat quality. Here, we performed whole genome resequencing on 516 yellow feather chickens and single-cell RNA sequencing on 3 63-day-old female JXY chickens. In addition, transcriptome sequencing techniques were also performed on breast muscle tissue of JXY chickens at different developmental stages. And 13C isotope tracing technique was applied. In this study, a large-scale genetic analysis of an IMF-selected population and a control population identified fatty acid synthase (FASN) as a key gene for improving IMF content. Also, contrary to conventional view, de novo lipogenesis (DNL) was deemed to be an important contributor to IMF deposition. As expected, further analyses by isotope tracing and other techniques, confirmed that DNL mainly occurs in myocytes, contributing about 40% of the total fatty acids through the regulation of FASN, using the available FAs as substrates. Additionally, we also identified a relevant causal mutation in the FASN gene with effects on FA composition. These findings contribute to the understanding of fat metabolism in muscle tissue of poultry, and provide the feasible strategy for the production of high-quality chicken meat. [ABSTRACT FROM AUTHOR]

Recent research has highlighted the essential role of the microbiome in maintaining skeletal muscle physiology. The microbiota influences muscle health by regulating lipid metabolism, protein synthesis, and insulin sensitivity. However, metabolic disturbances such as obesity can lead to dysbiosis, impairing muscle function. Time‐restricted feeding (TRF) has been shown to mitigate obesity‐related muscle dysfunction, but its effects on restoring healthy microbiomes remain poorly understood. This study utilizes 16S microbiome analysis and bacterial supplementation to investigate the bacterial communities influenced by TRF that may benefit skeletal muscle physiology. In wild‐type and obese Drosophila models (axenic models devoid of natural microbial communities), the absence of microbiota influence muscle performance and metabolism differently. Specifically, axenic wild‐type Drosophila exhibited reduced muscle performance, higher glucose levels, insulin resistance, ectopic lipid accumulation, and decreased ATP levels. Interestingly, in obese Drosophila (induced by a high‐fat diet or predisposed obesity mutant Sk2), the absence of microbiota improved muscle performance, lowered glucose levels, reduced insulin resistance, and increased ATP levels. TRF was found to modulate microbiota composition, notably increasing Acetobacter pasteurianus (AP) and decreasing Staphylococcus aureus (SA) in both obesity models. Supplementation with AP improved muscle performance and reduced glucose and insulin resistance, while SA supplementation had the opposite effect. This study provides novel insights into the complex interactions between TRF, microbiota, and skeletal muscle physiology in different Drosophila models. [ABSTRACT FROM AUTHOR]

Background: Amyotrophic lateral sclerosis (ALS) is a devastating and incurable neurodegenerative disease. Accumulating evidence strongly suggests that intrinsic muscle defects exist and contribute to disease progression, including imbalances in whole-body metabolic homeostasis. We have previously reported that tumour necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor inducible 14 (Fn14) are significantly upregulated in skeletal muscle of the SOD1G93A ALS mouse model. While antagonising TWEAK did not impact survival, we did observe positive effects in skeletal muscle. Given that Fn14 has been proposed as the main effector of the TWEAK/Fn14 activity and that Fn14 can act independently from TWEAK in muscle, we suggest that manipulating Fn14 instead of TWEAK in the SOD1G93A ALS mice could lead to differential and potentially improved benefits. Methods: We thus investigated the contribution of Fn14 to disease phenotypes in the SOD1G93A ALS mice. To do so, Fn14 knockout mice (Fn14−/−) were crossed onto the SOD1G93A background to generate SOD1G93A;Fn14−/− mice. Investigations were performed on both unexercised and exercised (rotarod and/or grid test) animals (wild type (WT), Fn14−/−, SOD1G93A and SOD1G93A;Fn14−/−). Results: Here, we firstly confirm that the TWEAK/Fn14 pathway is dysregulated in skeletal muscle of SOD1G93A mice. We then show that Fn14-depleted SOD1G93A mice display increased lifespan, myofiber size, neuromuscular junction endplate area as well as altered expression of known molecular effectors of the TWEAK/Fn14 pathway, without an impact on motor function. Importantly, we also observe a complex interaction between exercise (rotarod and grid test), genotype, disease state and sex that influences the overall effects of Fn14 deletion on survival, expression of known molecular effectors of the TWEAK/Fn14 pathway, expression of myosin heavy chain isoforms and myofiber size. Conclusions: Our study provides further insights on the different roles of the TWEAK/Fn14 pathway in pathological skeletal muscle and how they can be influenced by age, disease, sex and exercise. This is particularly relevant in the ALS field, where combinatorial therapies that include exercise regimens are currently being explored. As such, a better understanding and consideration of the interactions between treatments, muscle metabolism, sex and exercise will be of importance in future studies. [ABSTRACT FROM AUTHOR]

Near-infrared spectroscopy (NIRS) can be used to demonstrate muscle metabolism and oxygenation. NIRS-based oximeters enable the noninvasive measurement of static and dynamic muscle oxygenation. This study aimed to evaluate the relationship between NIRS readings and exercise capacity in group E COPD patients. The prospective study included 40 patients with group E COPD who presented to our outpatient clinic between May 2021 and June 2022. The patients were evaluated with pulmonary function testing, 6-Minute Walk Test (6MWT), echocardiography, and dyspnea and quality of life assessments. NIRS muscle oxygen saturation (SmO2) levels at the start and end of the 6MWT were obtained. 6MWT distance was positively correlated with intercostal SmO2 and fingertip SO2 at the start (R = 0.679, p ≤ 0.001 and R = 0.321, p = 0.04, respectively) and end of the 6MWT (R = 0.693, p ≤ 0.001 and R = 0.635, p ≤ 0.001, respectively) and negatively correlated with the number of hospitalizations due to exacerbations in the last year and mean pulmonary arterial pressure (R = − 0.648, p ≤ 0.001 and R = − 0.676, p ≤ 0.001, respectively). SF-36 score was positively correlated with intercostal SmO2 at the beginning of the 6MWT (R = 0.336, p = 0.03). Intercostal SmO2 levels at the start of the 6MWT positively correlated with diffusing capacity of the lung for carbon dioxide (DLCO) (R = 0.388, p = 0.01) and ratio of DLCO to alveolar volume (DLCO/VA) levels (R = 0.379, p = 0.02), and these correlations persisted more strongly after the 6MWT (R = 0.524, p = 0.01; R = 0.500, p = 0.01, respectively). NIRS is a practical and noninvasive method for measuring muscle oxygenation and can be used as an alternative to 6MWT in the evaluation of exercise capacity in patients with group E COPD. [ABSTRACT FROM AUTHOR]

Background and Purpose: There is a growing interest in use vibration foam rolling as a warm up and recovery tool. However, whether vibration foam rolling offers additional benefits to traditional foam rolling is unclear. The current study aims to compare the effects of acute foam rolling, with and without vibration, on skeletal muscle metabolism and microvascular reactivity. Methods: Fifteen physically active young males were tested on two different days, with gastrocnemius muscle microvascular function assessed using near-infrared spectroscopy coupled with the post-occlusive reactive hyperemia technique, before and after foam rolling, performed with or without vibration. The slope of tissue saturation index (TSI) decrease during occlusion between 120 s to 150 s (TSI occlusion slope) was assessed for muscle metabolic rate. Three commonly used microvascular function indexes, including the first10s TSI slope after occlusion (TSI10), time for TSI to reach half of peak magnitude (TSI1/2), and TSI peak reactive hyperemia, were also assessed. Results: None of the measured indexes showed significance for interaction or method (all p > 0.05). However, there was a main effect for time for TSI occlusion slope, TSI1/2, and TSI peak reactive hyperemia (p = 0.005, 0.034 and 0.046, respectively). No main effect for time for TSI10 was detected (p = 0.963). Conclusions: The application of foam rolling can decrease muscle metabolism, and may improve some aspects of muscle microvascular function. However, vibration foam rolling does not seem to offer any additional benefits compared to traditional foam rolling alone. [ABSTRACT FROM AUTHOR]

Glycine, the simple amino acid, is a key component of muscle metabolism with proven cytoprotective effects and hypothetical benefits as a therapeutic nutrient. Cell, in vitro, and animal studies suggest that glycine enhances protection against muscle wasting by activating anabolic pathways and inhibiting proteolytic gene expression. Some evidence indicates that glycine supplementation may enhance peak power output, reduce lactic acid accumulation during high-intensity exercise, and improve sleep quality and recovery. This literature review critically explores glycine's potential as an ergogenic aid and its relevance to muscle regeneration, muscle strength, endurance exercise performance, and sleep quality. It also underscores key areas for future research. It is concluded that more randomized controlled clinical trials in humans are needed to confirm glycine's potential as a dietary supplement to support muscle function, recovery, and overall athletic performance as an ergogenic aid and to establish nutritional recommendations for athletic performance. Also, it is essential to consider that high doses (>500 mg/kg of body mass) could induce cytotoxic effects and contribute to acute glutamate toxicity. [ABSTRACT FROM AUTHOR]

Background: There is a close relationship between breast muscle glucose metabolism, peripheral 5-hydroxytryptamine (5-HT), and myopathies in animals. Here, this study aimed to investigate the effects of different photoperiods on peripheral 5-HT metabolism, white striping (WS), and wooden breast (WB) in broilers. Methods: A total of 216 healthy 5-day-old (d) Arbor Acres (AA) male broilers were randomly assigned to 12L:12D, 18L:6D, and 24L:0D photoperiods for 4 weeks. Results: Compared with the 12L:12D photoperiod, we found the WB score in broilers was significantly increased in the 18L:6D and 24L:0D photoperiod at week 4 (p < 0.05). Muscle glycogen was significantly reduced (p < 0.05) and glycolysis was promoted in the breast muscles of broilers under the 18L:6D and 24L:0D photoperiods at week 2 and 4. Peripheral 5-HT concentrations, the mRNA expression of tryptophan hydroxylase 1 (TPH1) and serotonin transporter (SERT) in the cecal mucosa, and 5-hydroxytryptamine receptor 2A (5-HTR2A) mRNA expression in the breast muscle of broilers significantly up-regulated in the 18L:6D and 24L:0D photoperiod at week 2 and 4 (p < 0.05). Conclusions: Our findings revealed that extending the photoperiod improved the breast muscle growth rate, but up-regulated 5-HT synthesis and secretion to higher peripheral 5-HT, induced breast muscle glucose metabolism disorder, and increased WB incidence rates in broilers. [ABSTRACT FROM AUTHOR]

Compound 1 was previously identified by our team as a glycogen phosphorylase (GP) inhibitor with glucose-lowering activity and demonstrated to have protective effects against myocardial and cerebral ischemia. However, its impact on muscle function has not been clarified. This study is the first to evaluate the long-term effects of GP inhibitors on muscle function and metabolism. After a 28-day administration of Compound 1, we performed assays to assess muscle function and biochemical parameters in rats. We observed reductions in peak holding force, duration, tetanic contraction force, single-contraction force, and electromyographic signals under 20 s and 10 min contraction stimuli. The metabolic analysis showed no significant effects on muscle glycogen, ATP, lactic acid, and uric acid levels at low doses. In contrast, medium to high doses resulted in increased glycogen, decreased ATP, and reduced lactic acid (only at high doses), without affecting uric acid. These findings suggest that Compound 1 may adversely affect muscle function in rats, potentially due to the glycogen inhibition effects of GP inhibitors. This study provides crucial safety data and insights into the long-term effects of GP inhibitors on rat muscles, which will guide future developments and applications. [ABSTRACT FROM AUTHOR]

Obesity is a major global health concern. Studies suggest that the gut microflora may play a role in protecting against obesity. Probiotics, including lactic acid bacteria and Bifidobacterium, have garnered attention for their potential in obesity prevention. However, the effects of Bifidobacterium-fermented products on obesity have not been thoroughly elucidated. Bifidobacterium, which exists in the gut of animals, is known to enhance lipid metabolism. During fermentation, it produces acetic acid, which has been reported to improve glucose tolerance and insulin resistance, and exhibit anti-obesity and anti-diabetic effects. Functional foods have been very popular around the world, and fermented milk is a good candidate for enrichment with probiotics. In this study, we aim to evaluate the beneficial effects of milks fermented with Bifidobacterium strains on energy metabolism and obesity prevention. Three Bifidobacterium strains (Bif-15, Bif-30, and Bif-39), isolated from newborn human feces, were assessed for their acetic acid production and viability in milk. These strains were used to ferment milk. Otsuka–Long–Evans Tokushima Fatty (OLETF) rats administered Bif-15-fermented milk showed significantly lower weight gain compared to those in the water group. The phosphorylation of AMPK was increased and the expression of lipogenic genes was suppressed in the liver of rats given Bif-15-fermented milk. Additionally, gene expression related to respiratory metabolism was significantly increased in the soleus muscle of rats given Bif-15-fermented milk. These findings suggest that milk fermented with the Bifidobacterium strain Bif-15 can improve lipid metabolism and suppress obesity. [ABSTRACT FROM AUTHOR]

Background: Sarcopenia is a muscle disorder causing a progressive reduction of muscle mass and strength, but the mechanism of its manifestation is still partially unknown. The three main parameters to assess are: muscle strength, muscle volume or quality and low physical performance. There is not a definitive approach to assess the musculoskeletal condition of frail population and often the available tests to be performed in those clinical bedridden patients is reduced because of physical impairments. In this paper, we propose a novel instrumental multi-domain and non-invasive approach during a well-defined protocol of measurements for overcoming these limitations. A group of 28 bedridden elder people, subjected to surgery after hip fracture, was asked to perform voluntary isometric contractions at the 80% of their maximum voluntary contraction with the non-injured leg. The sensor employed before and/or during the exercise were: ultrasound to determine the muscle architecture (vastus lateralis); force acquisition with a load cell placed on the chair, giving an indication of the muscle strength; surface electromyography (EMG) for monitoring muscular electrical activity; time-domain (TD) near-infrared spectroscopy (NIRS) for evaluating muscle oxidative metabolism. Results: A personalized "report card" for each subject was created. It includes: the force diagram (both instantaneous and cumulative, expected and measured); the EMG–force diagram for a comparison between EMG derived median frequency and measured force; two graphs related to the hemodynamic parameters for muscle oxidative metabolism evaluation, i.e., oxy-, deoxy-, total-hemoglobin and tissue oxygen saturation for the whole exercise period. A table with the absolute values of the previous hemodynamic parameters during the rest and the ultrasound related parameters are also included. Conclusions: In this work, we present the union of protocols, multi-domain sensors and parameters for the evaluation of the musculoskeletal condition. The novelties are the use of sensors of different nature, i.e., force, electrical and optical, together with a new way to visualize and combine the results, by means of a concise, exhaustive and personalized medical report card for each patient. This assessment, totally non-invasive, is focused on a bedridden population, but can be extended to the monitoring of rehabilitation progresses or of the training of athletes. [ABSTRACT FROM AUTHOR]

Several metabolites have been shown to have independent and at times unexpected biological effects outside of their metabolic pathways. These include succinate, lactate, fumarate, and 2-hydroxyglutarate. 2-Hydroxybutyrate (2HB) is a byproduct of endogenous cysteine synthesis, produced during periods of cellular stress. 2HB rises acutely after exercise; it also rises during infection and is also chronically increased in a number of metabolic disorders. We show here that 2HB inhibits branched-chain aminotransferase enzymes, which in turn triggers a SIRT4-dependent shift in the compartmental abundance of protein ADP-ribosylation. The 2HB-induced decrease in nuclear protein ADP-ribosylation leads to a C/EBPβ-mediated transcriptional response in the branched-chain amino acid degradation pathway. This response to 2HB exposure leads to an improved oxidative capacity in vitro. We found that repeated injection with 2HB can replicate the improvement to oxidative capacity that occurs following exercise training. Together, we show that 2-HB regulates fundamental aspects of skeletal muscle metabolism. [ABSTRACT FROM AUTHOR]

Skeletal muscle function is vital for locomotion, posture, and metabolism, significantly impacting overall health and preventing falls, morbidity, and mortality, especially in elderly populations. This systematic review investigates the influence of hormonal fluctuations on skeletal muscle function across different life stages in women, including adolescence, the reproductive years, and menopause. A comprehensive literature search was conducted using databases such as PubMed, Scopus, and Web of Science to identify relevant studies. This review includes 45 studies that met the inclusion criteria, examining the roles of estrogen, progesterone, and other hormones in muscle metabolism, strength, and recovery. The findings highlight significant stage-specific hormonal impacts on muscle function, revealing how puberty, menstrual cycles, pregnancy, and menopause uniquely affect muscle health. Effective hormonal and non-hormonal interventions tailored to each life stage were identified, offering insights for optimizing muscle function and health management in women. This synthesis aims to bridge the gaps in understanding the hormonal regulation of muscle function, providing a foundation for future research and guiding clinical practices. [ABSTRACT FROM AUTHOR]

Metabolic diseases, notably obesity and type 2 diabetes (T2D), have reached alarming proportions and constitute a significant global health challenge, emphasizing the urgent need for effective preventive and therapeutic strategies. In contrast, exercise training emerges as a potent intervention, exerting numerous positive effects on metabolic health through adaptations to the metabolic tissues. Here, we reviewed the major features of our current understanding with respect to the intricate interplay between metabolic diseases and key metabolic tissues, including adipose tissue, skeletal muscle, and liver, describing some of the main underlying mechanisms driving pathogenesis, as well as the role of exercise to combat and treat obesity and metabolic disease. [ABSTRACT FROM AUTHOR]

Cancer cachexia, the unintentional loss of lean mass, contributes to functional dependency, poor treatment outcomes, and decreased survival. Although its pathogenicity is multifactorial, metabolic dysfunction remains a hallmark of cachexia. However, significant knowledge gaps exist in understanding the role of skeletal muscle lipid metabolism and dynamics in this condition. We examined skeletal muscle metabolic dysfunction, intramyocellular lipid droplet (LD) content, LD morphology and subcellular distribution, and LD-mitochondrial interactions using the Lewis lung carcinoma (LLC) murine model of cachexia. C57/BL6 male mice (n = 20) were implanted with LLC cells (106) in the right flank or underwent PBS sham injections. Skeletal muscle was excised for transmission electron microscopy (TEM; soleus), oil red O/lipid staining [tibialis anterior (TA)], and protein (gastrocnemius). LLC mice had a greater number (232%; P = 0.006) and size (130%; P = 0.023) of intramyocellular LDs further supported by increased oil-red O positive (87%; P = 0.0109) and "very high" oil-red O positive (178%; P = 0.0002) fibers compared with controls and this was inversely correlated with fiber size (R2 = 0.5294; P < 0.0001). Morphological analyses of LDs show increased elongation and complexity [aspect ratio: intermyofibrillar (IMF) = 9%, P = 0.046) with decreases in circularity [circularity: subsarcolemmal (SS) = 6%, P = 0.042] or roundness (roundness: whole = 10%, P = 0.033; IMF = 8%, P = 0.038) as well as decreased LD-mitochondria touch (−15%; P = 0.006), contact length (−38%; P = 0.036), and relative contact (86%; P = 0.004). Furthermore, dysregulation in lipid metabolism (adiponectin, CPT1b) and LD-associated proteins, perilipin-2 and perilipin-5, in cachectic muscle (P < 0.05) were observed. Collectively, we provide evidence that skeletal muscle myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in a preclinical model of cancer cachexia. NEW & NOTEWORTHY: We sought to advance our understanding of skeletal muscle lipid metabolism and dynamics in cancer cachexia. Cachexia increased the number and size of intramyocellular lipid droplets (LDs). Furthermore, decreases in LD-mitochondrial touch, contact length, and relative contact along with increased LD shape complexity with decreases in circularity and roundness. Dysregulation in lipid metabolism and LD-associated proteins was also documented. Collectively, we show that myosteatosis, altered LD morphology, and decreased LD-mitochondrial interactions occur in cancer cachexia. [ABSTRACT FROM AUTHOR]

Dairy cattle with high (HM) versus low muscle (LM) reserves as determined by longissimus dorsi muscle depth (LDD) in late gestation exhibit differential muscle mobilization related to subsequent milk production. Moreover, branched-chain volatile fatty acid (BCVFA) supplementation increased blood glucose levels. We hypothesized that differences in HM and LM reflect distinct muscle metabolism and that BCVFA supplementation altered metabolic pathways. At 42 days before expected calving (BEC), Holstein dairy cows were enrolled in a 2 × 2 factorial study of diet and muscle reserves, by assignment to control (CON)- or BCVFA-supplemented diets and LDD of HM (>4.6 cm) or LM (≤4.6 cm) groups: HM-CON (n = 13), HM-BCVFA (n = 10), LM-CON (n = 9), and LM-BCVFA (n = 9). Longisumus dorsi muscle was biopsied at 21 days BEC, total RNA was isolated, and protein-coding gene expression was measured with RNA sequencing. Between HM and LM, 713 genes were differentially expressed and 481 between BCVFA and CON (P < 0.05). Transcriptional signatures indicated differential distribution of type II fibers between groups, with MYH1 greater in LM cattle and MYH2 greater in HM cattle (P < 0.05). Signatures of LM cattle relative to HM cattle indicated greater activation of autophagy, ubiquitin-proteasome, and Ca2+-calpain pathways. HM cattle displayed greater expression of genes that encode extracellular matrix proteins and factors that regulate their proteolysis and turnover. BCVFA modified transcriptomes by increasing expression of genes that regulate fatty acid degradation and flux of carbons into the tricarboxylic acid cycle as acetyl CoA. Molecular signatures support distinct metabolic strategies between LM and HM cattle and that BCVFA supplementation increased substrates for energy generation. NEW & NOTEWORTHY: Muscle biopsies of the longissimus dorsi of prepartum dairy cattle indicate that molecular signatures support distinct metabolic strategies between low- and high-muscle cattle and that branched-chain volatile fatty acid supplementation increased substrates for energy generation. [ABSTRACT FROM AUTHOR]

Endurance exercise performance is known to be closely associated with the three physiological pillars of maximal O2 uptake (V̇O2max$\dot{V}_{{\rm O}_{2}{\rm max}}$), economy or efficiency during submaximal exercise, and the fractional utilisation of V̇O2max$\dot{V}_{{\rm O}_{2}{\rm max}}$ (linked to metabolic/lactate threshold phenomena). However, while 'start line' values of these variables are collectively useful in predicting performance in endurance events such as the marathon, it is not widely appreciated that these variables are not static but are prone to significant deterioration as fatiguing endurance exercise proceeds. For example, the 'critical power' (CP), which is a composite of the highest achievable steady‐state oxidative metabolic rate and efficiency (O2 cost per watt), may fall by an average of 10% following 2 h of heavy intensity cycle exercise. Even more striking is that the extent of this deterioration displays appreciable inter‐individual variability, with changes in CP ranging from <1% to ∼32%. The mechanistic basis for such differences in fatigue resistance or 'physiological resilience' are not resolved. However, resilience may be important in explaining superlative endurance performance and it has implications for the physiological evaluation of athletes and the design of interventions to enhance performance. This article presents new information concerning the dynamic plasticity of the three 'traditional' physiological variables and argues that physiological resilience should be considered as an additional component, or fourth dimension, in models of endurance exercise performance. [ABSTRACT FROM AUTHOR]

Poor maternal nutrition during gestation negatively affects offspring growth and metabolism. To evaluate the impact of maternal nutrient restriction and realimentation on metabolism in the fetal liver, skeletal muscle, and circulation, on day 50 of gestation, ewes (n = 48) pregnant with singletons were fed 100% (CON) or 60% (RES) of requirements until day 90 of gestation, when a subset of ewes (n = 7/treatment) were euthanized, and fetal samples were collected. The remaining ewes were maintained on a current diet (CON-CON, n = 6; RES-RES, n = 7) or switched to an alternative diet (CON-RES, RES-CON; n = 7/treatment). On day 130 of gestation, the remaining ewes were euthanized, and fetal samples were collected. Fetal liver, longissimus dorsi (LD), and blood metabolites were analyzed using LC-MS/MS, and pathway enrichment analysis was conducted using MetaboAnalyst. Then, 600, 518, and 524 metabolites were identified in the liver, LD, and blood, respectively, including 345 metabolites that were present in all three. Nutrient restriction was associated with changes in amino acid, carbohydrate, lipid, and transulfuration/methionine metabolic pathways, some of which were alleviated by realimentation. Fetal age also affected metabolite abundance. The differential abundance of metabolites involved in amino acid, methionine, betaine, and bile acid metabolism could impact fetal epigenetic regulation, protein synthesis, lipid metabolism, and signaling associated with glucose and lipid metabolism. [ABSTRACT FROM AUTHOR]

Background: Near-infrared spectroscopy (NIRS) technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise. Since this technology has been growing and is now successfully used in laboratory and sports settings, this systematic review aimed to synthesize the evidence and enhance an integrative understanding of blood flow adjustments and oxygen (O2) changes (i.e., the balance between O2 delivery and O2 consumption) within the cerebral and muscle systems during exercise. Methods: A systematic review was conducted using PubMed, Embase, Scopus, and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise. This review considered manuscripts written in English and available before February 9, 2023. Each step of screening involved evaluation by 2 independent authors, with disagreements resolved by a third author. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies. Results: Twenty studies were included, of which 80% had good methodological quality, and involved 290 young or middle-aged adults. Different types of exercises were used to assess cerebral and muscle hemodynamic changes, such as cycling (n = 11), treadmill (n = 1), knee extension (n = 5), isometric contraction of biceps brachii (n = 3), and duet swim routines (n = 1). The cerebral hemodynamics analysis was focused on the frontal cortex (n = 20), while in the muscle, the analysis involved vastus lateralis (n = 18), gastrocnemius (n = 3), biceps brachii (n = 5), deltoid (n = 1), and intercostal muscle (n = 1). Overall, muscle deoxygenation increases during exercise, reaching a plateau in voluntary exhaustion, while in the brain, oxyhemoglobin concentration increases with exercise intensity, reaching a plateau or declining at the exhaustion point. Conclusion: Muscle and cerebral oxygenation respond differently to exercise, with muscle increasing O2 utilization and cerebral tissue increasing O2 delivery during exercise. However, at the exhaustion point, both muscle and cerebral oxygenation become compromised. This is characterized by a reduction in blood flow and a decrease in O2 extraction in the muscle, while in the brain, oxygenation reaches a plateau or decline, potentially resulting in motor failure during exercise.

Abstract Background Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription of personalized exercise programs specifically designed to reverse the potential metabolic alterations in skeletal muscle could result in better results. Methods To test this hypothesis, we drew the metabolic signature of the fast-twitch quadriceps muscle, based on a combined unbiased NMR spectroscopy and RT-qPCR study, in several T2DM mouse models of different genetic background (129S1/SvImJ, C57Bl/6J), sex and aetiology (high-fat diet (HFD) or HFD/Streptozotocin (STZ) induction or transgenic MKR (FVB-Tg Ckm-IGF1R*K1003R)1Dlr/J) mice. Three selected mouse models with unique muscular metabolic signatures were submitted to three different swimming-based programs, designed to address each metabolic specificity. Results We found that depending on the genetic background, the sex, and the mode of T2DM induction, specific muscular adaptations occurred, including depressed glycolysis associated with elevated PDK4 expression, shift to β-oxidation, or deregulation of amino-acid homeostasis. Interestingly, dedicated swimming-based exercises designed to restore specific metabolic alterations in muscle were found optimal in improving systemic T2DM hallmarks, including a significant reduction in insulin resistance, the improvement of glucose homeostasis, and a delay in sensorimotor function alterations. Conclusion The muscle metabolism constitutes an important clue for the design of precision exercises with potential clinical implications for T2DM patients.

Simple Summary: The widespread use of antibiotics in poultry production has raised public concerns about food safety and meat quality. This study investigated the effects of early ciprofloxacin use on Xueshan chickens, focusing on growth, meat quality, and metabolic changes. It was found that, while ciprofloxacin treatment did not affect overall chicken growth, it significantly altered meat quality characteristics, which may affect meat texture and preservability. Although ciprofloxacin residues were not detected in muscle, metabolic analyses revealed significant metabolic alterations, particularly in microbial and amino acid metabolism pathways. These findings emphasize that antibiotic use may have far-reaching effects on poultry product quality, involving not only direct meat quality changes but also complex metabolic reactions. This study provides new perspectives for understanding the role of antibiotics in poultry production, which is important for optimizing antibiotic-use strategies and ensuring food safety. The results may be an important reference for poultry producers, food safety regulators and consumers. To investigate the effects of early administration of ciprofloxacin (CIP) on Xueshan chickens, in this study Xueshan chickens were measured for growth performance, tested for drug residues, evaluated for meat quality, and muscle metabolism changes were explored using a non-target metabolomics approach. Experimental findings revealed that early CIP use did not significantly impact the overall growth rate of Xueshan chickens (p > 0.05). However, notable alterations in meat quality were observed: the CIP-treated group exhibited a significant decrease in muscle pH (pH1 and pH24) and a marked increase in drip loss and moisture content (p > 0.05). No CIP residues were detected in muscle tissue. Untargeted metabolomics analyses unveiled significant alterations in the metabolic profile of market-age chickens following CIP treatment. Both functional enrichment and metabolic network analyses indicated significant effects on the ko01120 (microbial metabolism in diverse environments) and ko00350 (tyrosine metabolism) pathways, implying that CIP treatment may influence chicken meat quality by modulating microbial communities and amino acid metabolism. This study provides a crucial foundation for understanding the impact of antibiotics on meat quality and metabolism in poultry production, offering scientific insights for optimizing antibiotic-use strategies and safeguarding poultry product quality. [ABSTRACT FROM AUTHOR]

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) are novel antihyperglycemic agents. By acting through the central nervous system, they increase satiety and reduce food intake, thus lowering body weight. Furthermore, they increase the secretion of insulin while decreasing the production of glucagon. However, recent studies suggest a more complex metabolic impact through the interaction with various other tissues. In our present review, we aim to provide a summary of the effects of GLP-1 RA on serum lipids, adipose tissue, and muscle metabolism. It has been found that GLP-1 RA therapy is associated with decreased serum cholesterol levels. Epicardial adipose tissue thickness, hepatic lipid droplets, and visceral fat volume were reduced in obese patients with cardiovascular disease. GLP-1 RA therapy decreased the level of proinflammatory adipokines and reduced the expression of inflammatory genes. They have been found to reduce endoplasmic reticulum stress in adipocytes, leading to better adipocyte function and metabolism. Furthermore, GLP-1 RA therapy increased microvascular blood flow in muscle tissue, resulting in increased myocyte metabolism. They inhibited muscle atrophy and increased muscle mass and function. It was also observed that the levels of muscle-derived inflammatory cytokines decreased, and insulin sensitivity increased, resulting in improved metabolism. However, some clinical trials have been conducted on a very small number of patients, which limits the strength of these observations. [ABSTRACT FROM AUTHOR]

Thyroid hormone (TH) effects are mediated through TH receptors (TRs), TRα1, TRβ1, and TRβ2. The TRs bind to the DNA and regulate expression of TH target genes (canonical signaling). In addition, they mediate activation of signaling pathways (noncanonical signaling). Whether noncanonical TR action contributes to the spectrum of TH effects is largely unknown. The aim of this study was to attribute physiological effects to the TR isoforms and their canonical and noncanonical signaling. We conducted multiparameter phenotyping in male and female TR knockout mice (TRαKO, TRβKO), mice with disrupted canonical signaling due to mutations in the TR DNA binding domain (TRαGS, TRβGS), and their wild-type littermates. Perturbations in senses, especially hearing (mainly TRβ with a lesser impact of TRα), visual acuity, retinal thickness (TRα and TRβ), and in muscle metabolism (TRα) highlighted the role of canonical TR action. Strikingly, selective abrogation of canonical TR action often had little phenotypic consequence, suggesting that noncanonical TR action sufficed to maintain the wild-type phenotype for specific effects. For instance, macrocytic anemia, reduced retinal vascularization, or increased anxiety-related behavior were only observed in TRαKO but not TRαGS mice. Noncanonical TRα action improved energy utilization and prevented hyperphagia observed in female TRαKO mice. In summary, by examining the phenotypes of TRα and TRβ knockout models alongside their DNA binding–deficient mutants and wild-type counterparts, we could establish that the noncanonical actions of TRα and TRβ play a crucial role in modulating sensory, behavioral, and metabolic functions and, thus, contribute to the spectrum of physiological TH effects. [ABSTRACT FROM AUTHOR]

Muscle wasting can be caused by nutrition deficiency and inefficient metabolism of amino acids, including Branched Chain Amino Acids (BCAAs). Branched Chain Amino Acids are a major contributor to the metabolic needs of healthy muscle and account for over a tenth of lean muscle mass. Branched chain alpha-ketoacid dehydrogenase (BCKD) is the rate limiting enzyme of BCAA metabolism. Inhibition of BCKD is achieved through a reversible phosphorylation event by Branched Chain a-ketoacid dehydrogenase kinase (BCKDK). Our study set out to determine the importance of BCKDK in the maintenance of skeletal muscle. We used the Gene Expression Omnibus Database to understand the role of BCKDK in skeletal muscle pathogenesis, including aging, muscular disease, and interrupted muscle metabolism. We found BCKDK expression levels were consistently decreased in pathologic conditions. These results were most consistent when exploring muscular disease followed by aging. Based on our findings, we hypothesize that decreased BCKDK expression alters BCAA catabolism and impacts loss of normal muscle integrity and function. Further research could offer valuable insights into potential therapeutic strategies for addressing muscle-related disorders. [ABSTRACT FROM AUTHOR]

Plyometric training is characterized by high-intensity exercise which is performed in short term efforts divided into sets. The purpose of the present study was twofold: first, to investigate the effects of three distinct plyometric exercise protocols, each with varying work-to-rest ratios, on muscle fatigue and recovery using an incline-plane training machine; and second, to assess the relationship between changes in lower limb muscle strength and power and the biochemical response to the three exercise variants employed. Forty-five adult males were randomly divided into 3 groups (n = 15) performing an exercise of 60 rebounds on an incline-plane training machine. The G0 group performed continuous exercise, while the G45 and G90 groups completed 4 sets of 15 repetitions, each set lasting 45 s with 45 s rest in G45 (work-to-rest ratio of 1:1) and 90 s rest in G90 (1:2 ratio). Changes in muscle torques of knee extensors and flexors, as well as blood lactate (LA) and ammonia levels, were assessed before and every 5 min for 30 min after completing the workout. The results showed significantly higher (p < 0.001) average power across all jumps generated during intermittent compared to continuous exercise. The greatest decrease in knee extensor strength immediately post-exercise was recorded in group G0 and the least in G90. The post-exercise time course of LA changes followed a similar pattern in all groups, while the longer the interval between sets, the faster LA returned to baseline. Intermittent exercise had a more favourable effect on muscle energy metabolism and recovery than continuous exercise, and the work-to-rest ratio of 1:2 in plyometric exercises was sufficient rest time to allow the continuation of exercise in subsequent sets at similar intensity. [ABSTRACT FROM AUTHOR]

• Moringa oleifera's effect on energy metabolism. • CN Mowa. Moringa oleifera (M. oleifera) is a subtropical plant routinely used to treat inflammation and chronic disease. However, the mechanism of action of M. oleifera has not been fully elucidated. Thus, this study aims to evaluate its role as a novel ergogenic aid to improve exercise performance by driving signaling pathways implicated in mitochondrial biogenesis and oxidative metabolism in skeletal muscle tissue. To accomplish this, adult male C57BL/6 mice were treated with 1.0 g of M. oleifera (N = 20) per day or vehicle control (N = 20) for five weeks. Following three weeks of supplementation, half of each group (RUN) was given access to running wheels every night for two weeks (Remaining half = SED). After treatment protocols were complete, the gastrocnemius muscles were excised and assayed for markers of mitochondrial biogenesis, angiogenesis, endurance capacity, and capillary density using immunohistochemistry and RT-PCR. Our results showed a significant increase in average distance run in the M. oleifera + RUN compared to SED mice. In addition, key metabolic markers such as PGC-1α, PPARγ, SDHB, SUCLG1, VEGF, PGAM-2, PGK1, and MYLPF were increased in the M. oleifera treated groups compared to vehicle + SED. Moreover, M. oleifera also increased CSA and decreased markers of protein degradation. This data suggests that M. oleifera has the potential to be an ergogenic aid that enhances energy metabolism in adult skeletal muscle by increasing the expression of key metabolic markers. [ABSTRACT FROM AUTHOR]

• The findings are consistent in showing greater deoxygenation in the muscles during exercise, reflecting the oxygen (O 2) utilization. • Muscle O 2 availability becomes compromised when an individual reaches the exhaustion point by reducing blood flow and decreasing muscle O 2 extraction. • Cerebral tissue experiences an increase in O 2 delivery with increased exercise intensity, suggesting a greater engagement of the brain areas to sustain the exercise. • At the exhaustion point, cerebral oxygenation reaches a plateau or decline, potentially resulting in motor failure during exercise. Near-infrared spectroscopy (NIRS) technology has allowed for the measurement of cerebral and skeletal muscle oxygenation simultaneously during exercise. Since this technology has been growing and is now successfully used in laboratory and sports settings, this systematic review aimed to synthesize the evidence and enhance an integrative understanding of blood flow adjustments and oxygen (O 2) changes (i.e., the balance between O 2 delivery and O 2 consumption) within the cerebral and muscle systems during exercise. A systematic review was conducted using PubMed, Embase, Scopus, and Web of Science databases to search for relevant studies that simultaneously investigated cerebral and muscle hemodynamic changes using the near-infrared spectroscopy system during exercise. This review considered manuscripts written in English and available before February 9, 2023. Each step of screening involved evaluation by 2 independent authors, with disagreements resolved by a third author. The Joanna Briggs Institute Critical Appraisal Checklist was used to assess the methodological quality of the studies. Twenty studies were included, of which 80% had good methodological quality, and involved 290 young or middle-aged adults. Different types of exercises were used to assess cerebral and muscle hemodynamic changes, such as cycling (n = 11), treadmill (n = 1), knee extension (n = 5), isometric contraction of biceps brachii (n = 3), and duet swim routines (n = 1). The cerebral hemodynamics analysis was focused on the frontal cortex (n = 20), while in the muscle, the analysis involved vastus lateralis (n = 18), gastrocnemius (n = 3), biceps brachii (n = 5), deltoid (n = 1), and intercostal muscle (n = 1). Overall, muscle deoxygenation increases during exercise, reaching a plateau in voluntary exhaustion, while in the brain, oxyhemoglobin concentration increases with exercise intensity, reaching a plateau or declining at the exhaustion point. Muscle and cerebral oxygenation respond differently to exercise, with muscle increasing O 2 utilization and cerebral tissue increasing O 2 delivery during exercise. However, at the exhaustion point, both muscle and cerebral oxygenation become compromised. This is characterized by a reduction in blood flow and a decrease in O 2 extraction in the muscle, while in the brain, oxygenation reaches a plateau or decline, potentially resulting in motor failure during exercise. [Display omitted] [ABSTRACT FROM AUTHOR]

Skeletal muscle metabolism has implications for swine feed efficiency (FE); however, it remains unclear if the metabolic profile of skeletal muscle changes during postnatal growth. To assess the metabolic changes, samples were collected from the longissimus dorsi (LD, glycolytic muscle), latissimus dorsi (LAT, mixed muscle), and masseter (MS, oxidative muscle) at 20, 53, 87, 120, and 180 days of age from barrows. Muscles were assessed to determine the abundance of several metabolic enzymes. Lactate dehydrogenase (LDHα) decreased in all muscles from 20 to 87 d (p < 0.01), which may be attributed to the muscles being more glycolytic at weaning from a milk-based diet. Pyruvate carboxylase (PC) increased in all muscles at 53 d compared to the other time points (p < 0.01), while pyruvate dehydrogenase α 1 (PDHα1) increased at 87 and 180 d in MS compared to LD (p < 0.05), indicating that potential changes occur in pyruvate entry into the tricarboxylic acid (TCA) cycle during growth. Isolated mitochondria from each muscle were incubated with 13C-labeled metabolites to assess isotopomer enrichment patterns of TCA intermediates. Citrate M + 2 and M + 4 derived from [13C3]-pyruvate increased at 87 d in LAT and MS mitochondria compared to LD mitochondria (p < 0.05). Regardless of the muscle, citrate M+3 increased at 87 d compared to 20, 53, and 120 d, while 180 d showed intermediate values (p < 0.01). These data support the notion that pyruvate metabolism is dynamic during growth. Our findings establish a metabolic fingerprint associated with postnatal muscle hypertrophy. [ABSTRACT FROM AUTHOR]

Cyprinus carpio is a significant freshwater species with substantial nutritional and economic value. Rice–carp co-culture represents one of its principal cultivation methods. However, in the system, the optimal farming density for carp and the impact of high stocking density on their muscle nutritional composition have yet to be explored. Thus, the objective of the current study was to investigate the influences of stocking density on the muscle nutrient profiles and metabolism of C. carpio in rice–fish co-culture systems. Common carp were cultured at three stocking densities, low density (LD), medium density (MD), and high density (HD), over a period of 60 days. Following this, comprehensive analyses incorporating physiological, biochemical, and multi-omics sequencing were conducted on the muscle tissue of C. carpio. The results demonstrated that HD treatment led to a reduction in the antioxidant capacity of C. carpio, while resulting in elevated levels of various fatty acids in muscle tissue, including saturated fatty acids (SFAs), omega-3 polyunsaturated fatty acids (n-3 PUFAs), and omega-6 polyunsaturated fatty acids (n-6 PUFAs). The metabolome analysis showed that HD treatment caused a marked reduction in 43 metabolites and a significant elevation in 30 metabolites, primarily linked to lipid and amino acid metabolism. Additionally, transcriptomic analysis revealed that the abnormalities in lipid metabolism induced by high-stocking-density treatment may be associated with significant alterations in the PPAR signaling pathway and adipokine signaling pathway. Overall, our findings indicate that in rice–fish co-culture systems, high stocking density disrupted the balance of antioxidant status and lipid metabolism in the muscles of C. carpio. [ABSTRACT FROM AUTHOR]

Obesity is a complex disease associated with augmented risk of metabolic disorder development and cellular dysfunction in various species. The goal of the present study was to investigate the impacts of obesity on the metabolic health of old mares as well as test the ability of diet supplementation with either a complex blend of nutrients designed to improve equine metabolism and gastrointestinal health or L-carnitine alone to mitigate negative effects of obesity. Mares (n = 19, 17.9 ± 3.7 years) were placed into one of three group: normal-weight (NW, n = 6), obese (OB, n = 7) or obese fed a complex diet supplement for 12 weeks (OBD, n = 6). After 12 weeks and completion of sample collections, OB mares received L-carnitine alone for an additional 6 weeks. Obesity in mares was significantly associated with insulin dysregulation, reduced muscle mitochondrial function, and decreased skeletal muscle oxidative capacity with greater ROS production when compared to NW. Obese mares fed the complex diet supplement had better insulin sensivity, greater cell lipid metabolism, and higher muscle oxidative capacity with reduced ROS production than OB. L-carnitine supplementation alone did not significantly alter insulin signaling, but improved lipid metabolism and muscle oxidative capacity with reduced ROS. In conclusion, obesity is associated with insulin dysregulation and altered skeletal muscle metabolism in older mares. However, dietary interventions are an effective strategy to improve metabolic status and skeletal muscle mitochondrial function in older mares. [ABSTRACT FROM AUTHOR]

Iron is essential for cell respiration, muscle metabolism, and oxygen transport. Recent research has shown that simulated microgravity rapidly affects iron metabolism in men. However, its impact on women remains unclear. This study aims to compare iron metabolism alterations in both sexes exposed to 5 days of dry immersion. Our findings demonstrate that women, similarly to men, experience increased systemic iron availability and elevated serum hepcidin levels, indicative of iron misdistribution after short-term exposure to simulated microgravity. [ABSTRACT FROM AUTHOR]

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disease that commonly results from a high-calorie diet and sedentary lifestyle, leading to insulin resistance and glucose homeostasis perturbation. Physical activity is recommended as one first-line treatment in T2DM, but it leads to contrasted results. We hypothesized that, instead of applying standard exercise protocols, the prescription of personalized exercise programs specifically designed to reverse the potential metabolic alterations in skeletal muscle could result in better results. Methods: To test this hypothesis, we drew the metabolic signature of the fast-twitch quadriceps muscle, based on a combined unbiased NMR spectroscopy and RT-qPCR study, in several T2DM mouse models of different genetic background (129S1/SvImJ, C57Bl/6J), sex and aetiology (high-fat diet (HFD) or HFD/Streptozotocin (STZ) induction or transgenic MKR (FVB-Tg Ckm-IGF1R*K1003R)1Dlr/J) mice. Three selected mouse models with unique muscular metabolic signatures were submitted to three different swimming-based programs, designed to address each metabolic specificity. Results: We found that depending on the genetic background, the sex, and the mode of T2DM induction, specific muscular adaptations occurred, including depressed glycolysis associated with elevated PDK4 expression, shift to β-oxidation, or deregulation of amino-acid homeostasis. Interestingly, dedicated swimming-based exercises designed to restore specific metabolic alterations in muscle were found optimal in improving systemic T2DM hallmarks, including a significant reduction in insulin resistance, the improvement of glucose homeostasis, and a delay in sensorimotor function alterations. Conclusion: The muscle metabolism constitutes an important clue for the design of precision exercises with potential clinical implications for T2DM patients. [ABSTRACT FROM AUTHOR]

Sarcopenia burdens the older population through loss of muscle energy and mass, yet treatments to functionally rescue both parameters are lacking. The glucocorticoid prednisone remodels muscle metabolism on the basis of frequency of intake, but its mechanisms in sarcopenia are unknown. We found that once-weekly intermittent prednisone administration rescued muscle quality in aged 24-month-old mice to a level comparable to that seen in young 4-month-old mice. We discovered an age- and sex-independent glucocorticoid receptor transactivation program in muscle encompassing peroxisome proliferator-activated receptor γ coactivator 1 α (PGC1α) and its cofactor Lipin1. Treatment coordinately improved mitochondrial abundance through isoform 1 and muscle mass through isoform 4 of the myocyte-specific PGC1α, which was required for the treatmentdriven increase in carbon shuttling from glucose oxidation to amino acid biogenesis. We also probed myocyte-specific Lipin1 as a nonredundant factor coaxing PGC1α upregulation to the stimulation of both oxidative and anabolic effects. Our study unveils an aging-resistant druggable program in myocytes for the coordinated rescue of energy and mass in sarcopenia. [ABSTRACT FROM AUTHOR]

Carbohydrates and lipids provide the majority of substrates to fuel mitochondrial oxidative phosphorylation. Metabolic inflexibility, defined as an impaired ability to switch between these fuels, is implicated in a number of metabolic diseases. Here, we explore the mechanism by which physical inactivity promotes metabolic inflexibility in skeletal muscle. We developed a mouse model of sedentariness, small mouse cage (SMC), that, unlike other classic models of disuse in mice, faithfully recapitulated metabolic responses that occur in humans. Bioenergetic phenotyping of skeletal muscle mitochondria displayed metabolic inflexibility induced by physical inactivity, demonstrated by a reduction in pyruvate-stimulated respiration (JO2) in the absence of a change in palmitate-stimulated JO2. Pyruvate resistance in these mitochondria was likely driven by a decrease in phosphatidylethanolamine (PE) abundance in the mitochondrial membrane. Reduction in mitochondrial PE by heterozygous deletion of phosphatidylserine decarboxylase (PSD) was sufficient to induce metabolic inflexibility measured at the whole-body level, as well as at the level of skeletal muscle mitochondria. Low mitochondrial PE in C2C12 myotubes was sufficient to increase glucose flux toward lactate. We further implicate that resistance to pyruvate metabolism is due to attenuated mitochondrial entry via mitochondrial pyruvate carrier (MPC). These findings suggest a mechanism by which mitochondrial PE directly regulates MPC activity to modulate metabolic flexibility in mice. [ABSTRACT FROM AUTHOR]

Objective: Jining Grey goat is a local Chinese goat breed that is well known for its high fertility and excellent meat quality but shows low meat production performance. Numerous studies have focused on revealing the genetic mechanism of its high fertility, but its highlighting meat quality and muscle growth mechanism still need to be studied. Methods: In this research, an integrative analysis of the genomics and transcriptomics of Jining Grey goats compared with Boer goats was performed to identify candidate genes and pathways related to the mechanisms of meat quality and muscle development. Results: Our results overlap among five genes (ABHD2, FN1, PGM2L1, PRKAG3, RAVER2) and detected a set of candidate genes associated with fatty acid metabolism (PRKAG3, HADHB, FASN, ACADM), amino acid metabolism (KMT2C, PLOD3, NSD2, SETDB1, STT3B, MAN1A2, BCKDHB, NAT8L, P4HA3) and muscle development (MSTN, PPARGC1A, ANKRD2). Several pathways have also been detected, such as the FoxO signaling pathway and Apelin signaling pathway that play roles in lipid metabolism, lysine degradation, N-glycan biosynthesis, valine, leucine and isoleucine degradation that involving with amino acid metabolism. Conclusion: The comparative genomic and transcriptomic analysis of Jining Grey goat and Boer goat revealed the mechanisms underlying the meat quality and meat productive performance of goats. These results provide valuable information for future breeding of goats. [ABSTRACT FROM AUTHOR]

Combining proton and phosphorus magnetic resonance spectroscopy offers a unique opportunity to study the oxidative and glycolytic components of metabolism in working muscle. This paper presents a 7 T proton calf coil design that combines dipole and loop elements to achieve the high performance necessary for detecting metabolites with low abundance and restricted visibility, specifically lactate, while including the option of adding a phosphorus array. We investigated the transmit, receive, and parallel imaging performance of three transceiver dipoles with six pair-wise overlap-decoupled standard or twisted pair receive-only coils. With a higher SNR and more efficient transmission decoupling, standard loops outperformed twisted pair coils. The dipoles with standard loops provided a four-fold-higher image SNR than a multinuclear reference coil comprising two proton channels and 32% more than a commercially available 28-channel proton knee coil. The setup enabled up to three-fold acceleration in the right–left direction, with acceptable g-factors and no visible aliasing artefacts. Spectroscopic phantom measurements revealed a higher spectral SNR for lactate with the developed setup than with either reference coil and fewer restrictions in voxel placement due to improved transmit homogeneity. This paper presents a new use case for dipoles and highlights their advantages for the integration in multinuclear calf coils. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of a 4-week live high train low (LHTL; FiO2 ~ 13.5%), intervention, followed by a tapering phase, on muscle glycogen concentration. Fourteen physically active males (28 ± 6 years, 81.6 ± 15.4 kg, 179 ± 5.2 cm) were divided into a control group (CON; n = 5), and the group that performed the LHTL, which was exposed to hypoxia (LHTL; n = 9). The subjects trained using a one-legged knee extension exercise, which enabled four experimental conditions: leg training in hypoxia (TLHYP); leg control in hypoxia (CLHYP, n = 9); leg trained in normoxia (TLNOR, n = 5), and leg control in normoxia (CLNOR, n = 5). All participants performed 18 training sessions lasting between 20 and 45 min [80–200% of intensity corresponding to the time to exhaustion (TTE) reached in the graded exercise test]. Additionally, participants spent approximately 10 h day−1 in either a normobaric hypoxic environment (14.5% FiO2; ~ 3000 m) or a control condition (i.e., staying in similar tents on ~ 530 m). Thereafter, participants underwent a taper protocol consisting of six additional training sessions with a reduced training load. SpO2 was lower, and the hypoxic dose was higher in LHTL compared to CON (p < 0.001). After 4 weeks, glycogen had increased significantly only in the TLNOR and TLHYP groups and remained elevated after the taper (p < 0.016). Time to exhaustion in the LHTL increased after both the 4-week training period and the taper compared to the baseline (p < 0.001). Although the 4-week training promoted substantial increases in muscle glycogen content, TTE increased in LHTL condition. [ABSTRACT FROM AUTHOR]

Simple Summary: This meta-analysis examines the impact of neutering on sheep production and quality, focusing on performance, carcass characteristics, and meat quality. It is observed that castrated sheep (wethers) exhibit enhanced daily weight gain and meat tenderness compared to intact rams. Furthermore, wethers display characteristics of a slenderer carcass with potentially elevated muscle content. By utilizing gene expression analysis, the research sheds light on genes associated with metabolic pathways and fat metabolism, indicating their involvement in fat formation. These results advocate for the practice of castration in sheep farming to enhance growth and meat quality. Additionally, the identified alterations in gene expression offer valuable insights for further exploration of castration's influence on muscle development in sheep. Objective: The study aimed to investigate the effects of castration on performance, carcass characteristics, and meat quality in sheep, as well as explore the expression of key genes related to metabolic pathways and muscle growth following castration. Methods: A meta-analysis approach was utilized to analyze data from multiple studies to compare the performance, carcass characteristics, and meat quality of castrated sheep (wethers) with intact rams. Additionally, protein–protein interaction (PPI) networks, differential gene expression (DEG) interactions, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were examined to identify molecular mechanisms associated with fat metabolism and muscle development in sheep tails. Results: The analysis revealed that castrated sheep (wethers) exhibited improved average daily gain, increased tenderness, lower backfat thickness, and a tendency for greater loin muscle area compared to intact rams. This suggests that castration promotes faster growth and results in leaner carcasses with potentially higher muscle content. Furthermore, the identification of downregulated DEGs like ACLY, SLC27A2, and COL1A1 and upregulated DEGs such as HOXA9, PGM2L1, and ABAT provides insights into the molecular mechanisms underlying fat deposition and muscle development in sheep. Conclusions: The findings support the practice of castration in sheep production as it enhances growth performance, leads to leaner carcasses with higher muscle content, and improves meat tenderness. The identified changes in gene expression offer valuable insights for further research into understanding the impact of castration on muscle development and fat metabolism in sheep. This meta-analysis contributes to the knowledge of molecular mechanisms involved in fat deposition in sheep, opening avenues for future investigations in livestock fat metabolism research. [ABSTRACT FROM AUTHOR]

One of the most important processes that occur during the transformation of muscle to meat is the pH decline as a consequence of the post‐mortem metabolism of muscle tissue. Abnormal pH declines lead to pork defects such as pale, soft, and exudative meat. There is genetic variance for ultimate pH and the role of some genes on this phenotype is well established. After conducting a genome‐wide association study on ultimate pH using 526 purebred Duroc pigs, we identified associated regions on Sus scrofa chromosomes (SSC) 3, 8, and 15. Functional candidate genes in these regions included PRKAG3 and PHKG1. The SSC8 region, at 71.6 Mb, was novel and, although no candidate causative gene could be identified, it may have regulatory effects. Subsequent analysis on 828 pigs from the same population confirmed the impact of the three associated regions on pH and meat color. We detected no interaction between the three regions. Further investigations are necessary to unravel the functional significance of the novel genomic region at SSC8. These variants could be used as markers in marker‐assisted selection for improving meat quality. [ABSTRACT FROM AUTHOR]

Numerous research studies have shown that moderate physical exercise exerts positive effects on gastrointestinal tract health and increases the variety and relative number of beneficial microorganisms in the intestinal microbiota. Increasingly, studies have shown that the gut microbiota is critical for energy metabolism, immunological response, oxidative stress, skeletal muscle metabolism, and the regulation of the neuroendocrine system, which are significant for the physiological function of exercise. Dietary modulation targeting the gut microbiota is an effective prescription for improving exercise performance and alleviating exercise fatigue. This article discusses the connection between exercise and the makeup of the gut microbiota, as well as the detrimental effects of excessive exercise on gut health. Herein, we elaborate on the possible mechanism of the gut microbiota in improving exercise performance, which involves enhancing skeletal muscle function, reducing oxidative stress, and regulating the neuroendocrine system. The effects of dietary nutrition strategies and probiotic supplementation on exercise from the perspective of the gut microbiota are also discussed in this paper. A deeper understanding of the potential mechanism by which the gut microbiota exerts positive effects on exercise and dietary nutrition recommendations targeting the gut microbiota is significant for improving exercise performance. However, further investigation is required to fully comprehend the intricate mechanisms at work. [ABSTRACT FROM AUTHOR]

Sodium Danshensu (SDSS) is extracted from Salvia miltiorrhiza and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4 days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8 weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain (MyHCs) gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the MyHC1 and MyHC2a genes increased while MyHC2b expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited MyHC1 and MyHC2a expression but promoted MyHC2b expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production.

Estrogen is imperative to mammalian reproductivity, metabolism, and aging. However, the hormone activating estrogen receptor (ERs) α can cause major safety concerns due to the enrichment of ERα in female tissues and certain malignancies. In contrast, ERβ is more broadly expressed in metabolic tissues and the skin. Thus, it is desirable to generate selective ERβ agonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ERα activation. Here, we report the design and production of small molecule conjugates containing selective non-steroid ERβ agonists Gtx878 or genistein. Treatment of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity, visceral adipose integrity, skeletal muscle function, and skin health, with validation in vitro. We further uncovered the benefits of ERβ conjugates in the skin using two inducible skin injury mouse models, showing increased skin basal cell proliferation, epidermal thickness, and wound healing. Therefore, our ERβ-selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health.

The environmental impact of increased eutrophication and frequent cyanobacterial blooms on the growth and reproduction of aquatic organisms has become increasingly prominent in recent years. Bellamya aeruginosa is a nutrient-rich aquatic snail consumed by humans, and environmental changes may decrease its meat quality. However, the specific characteristics of muscle metabolism and flavor quality in freshwater snails and their response patterns to bloom-forming cyanobacterial stress have not been reported. Therefore, in this study, alterations in metabolites in the snail muscle after following feeding on toxic Microcystis aeruginosa were investigated using untargeted metabolomics. A total of 1,128 metabolites were identified, and the metabolic pathways of unsaturated fatty acid biosynthesis and purine, glutathione, and glycerophospholipid metabolism in snails fed toxic cyanobacteria differed from those in snails fed Chlorella vulgaris. Quantitative analysis showed increased levels of bitter-free amino acids, such as tyrosine, phenylalanine, and histidine, after consuming toxic cyanobacteria for 42 d, whereas a relative decrease was observed in the levels of umami- and sweet-free amino acids, such as glutamic acid, aspartic acid, serine, threonine, and glicine. The muscles of snails fed toxic cyanobacteria exhibited higher hypoxanthine and hypoxanthine nucleoside and lower adenosine triphosphate, adenine nucleotide, adenine nucleoside diphosphate, and hypoxanthine nucleotide contents than those of snails fed C. vulgaris. Furthermore, increased metabolites, such as stearic acid, palmitic acid, and cytidine diphosphate choline, and decreased metabolites, such as docosapentaenoic acid, docosahexaenoic acid, adrenoic acid, and L-glutamic acid, reflect the harmful effects of toxic cyanobacteria on the nutritional value and flesh quality of B. aeruginosa. This study comprehensively evaluated the effects of cyanobacterial blooms on freshwater gastropods, providing an important theoretical basis for the quality, safety, and sustainable development of snails as food and related processing industries. [ABSTRACT FROM AUTHOR]

This study investigated the effects of EPO on hemoglobin (Hgb) and hematocrit (Hct), time trial (TT) performance, substrate oxidation, and skeletal muscle phenotype throughout 28 days of strenuous exercise. Eight males completed this longitudinal controlled exercise and feeding study using EPO (50 IU/kg body mass) 3×/week for 28 days. Hgb, Hct, and TT performance were assessed PRE and on Days 7, 14, 21, and 27 of EPO. Rested/fasted muscle obtained PRE and POST EPO were analyzed for gene expression, protein signaling, fiber type, and capillarization. Substrate oxidation and glucose turnover were assessed during 90‐min of treadmill load carriage (LC; 30% body mass; 55 ± 5% V̇O2peak) exercise using indirect calorimetry, and 6‐6‐[2H2]‐glucose PRE and POST. Hgb and Hct increased, and TT performance improved on Days 21 and 27 compared to PRE (p < 0.05). Energy expenditure, fat oxidation, and metabolic clearance rate during LC increased (p < 0.05) from PRE to POST. Myofiber type, protein markers of mitochondrial biogenesis, and capillarization were unchanged PRE to POST. Transcriptional regulation of mitochondrial activity and fat metabolism increased from PRE to POST (p < 0.05). These data indicate EPO administration during 28 days of strenuous exercise can enhance aerobic performance through improved oxygen carrying capacity, whole‐body and skeletal muscle fat metabolism. [ABSTRACT FROM AUTHOR]

Myosteatosis, or the infiltration of fatty deposits into skeletal muscle, occurs with advancing age and contributes to the health and functional decline of older adults. Myosteatosis and its inflammatory milieu play a larger role in adipose tissue dysfunction, muscle tissue dysfunction, and increased passive muscle stiffness. Combined with the age‐related decline of sex hormones and development of anabolic resistance, myosteatosis also contributes to insulin resistance, impaired muscle mechanics, loss of force production from the muscle, and increased risk of chronic disease. Due to its highly inflammatory secretome and the downstream negative effects on muscle metabolism and mechanics, myosteatosis has become an area of interest for aging researchers and clinicians. Thus far, myosteatosis treatments have had limited success, as many lack the potency to completely rescue the metabolic and physical consequences of myosteatosis. Future research is encouraged for the development of reliable assessment methods for myosteatosis, as well as the continued exploration of pharmacological, nutritional, and exercise‐related interventions that may lead to the success in attenuating myosteatosis and its clinical consequences within the aging population. [ABSTRACT FROM AUTHOR]

The skeletal muscles account for approximately 40% of the body weight and are crucial in movement, nutrient absorption, and energy metabolism. Muscle loss and decline in function cause a decrease in the quality of life of patients and the elderly, leading to complications that require early diagnosis. Positron emission tomography/computed tomography (PET/CT) offers non-invasive, high-resolution visualization of tissues. It has emerged as a promising alternative to invasive diagnostic methods and is attracting attention as a tool for assessing muscle function and imaging muscle diseases. Effective imaging of muscle function and pathology relies on appropriate radiopharmaceuticals that target key aspects of muscle metabolism, such as glucose uptake, adenosine triphosphate (ATP) production, and the oxidation of fat and carbohydrates. In this review, we describe how [18F]fluoro-2-deoxy-D-glucose ([18F]FDG), [18F]fluorocholine ([18F]FCH), [11C]acetate, and [15O]water ([15O]H2O) are suitable radiopharmaceuticals for diagnostic imaging of skeletal muscles. [ABSTRACT FROM AUTHOR]

Estrogen is imperative to mammalian reproductivity, metabolism, and aging. However, the hormone activating estrogen receptor (ERs) α can cause major safety concerns due to the enrichment of ER α in female tissues and certain malignancies. In contrast, ER β is more broadly expressed in metabolic tissues and the skin. Thus, it is desirable to generate selective ER β agonist conjugates for maximizing the therapeutic effects of ERs while minimizing the risks of ER α activation. Here, we report the design and production of small molecule conjugates containing selective non-steroid ER β agonists Gtx878 or genistein. Treatment of aged mice with our synthesized conjugates improved aging-associated declines in insulin sensitivity, visceral adipose integrity, skeletal muscle function, and skin health, with validation in vitro. We further uncovered the benefits of ER β conjugates in the skin using two inducible skin injury mouse models, showing increased skin basal cell proliferation, epidermal thickness, and wound healing. Therefore, our ER β -selective agonist conjugates offer novel therapeutic potential to improve aging-associated conditions and aid in rejuvenating skin health. The use of selective estrogen receptor β conjugate agonists in mice provides anti-aging benefits in metabolism and skin health. [Display omitted] [ABSTRACT FROM AUTHOR]