Muscle Metabolism Research Articles

Inhibition of the ubiquitin-proteasome system reduces the abundance of pyruvate dehydrogenase kinase 1 in cultured myotubes

Pyruvate dehydrogenase kinase (PDK), which phosphorylates the pyruvate dehydrogenase complex, regulates glucose metabolism in skeletal muscle. PDK1, an isozyme whose expression is controlled by hypoxia-inducible factor-1α (HIF-1α), is thought to play a role in muscle adaptation to hypoxia. While transcriptional upregulation of PDK1 by HIF-1α is well characterised, mechanisms controlling proteolysis of PDK1 in skeletal muscle have not been thoroughly investigated. Proteasome inhibitor MG132 paradoxically reduced the abundance of PDK1 in human cancer cells and rat L6 myotubes, suggesting that MG132 might direct PDK1 towards autophagic degradation. The objectives of our current study were to determine (1) whether MG132 suppresses PDK1 levels in primary human myotubes, (2) whether chloroquine, an inhibitor of autophagy, prevents MG132-induced suppression of PDK1 in L6 myotubes, and (3) whether PYR-41, an inhibitor of ubiquitination, suppresses PDK1 in L6 myotubes. Using qPCR and/or immunoblotting, we found that despite markedly upregulating HIF-1α protein, MG132 did not alter the PDK1 expression in cultured primary human myotubes, while it suppressed both PDK1 mRNA and protein in L6 myotubes. The PDK1 levels in L6 myotubes were suppressed also during co-treatment with chloroquine and MG132. PYR-41 markedly increased the abundance of HIF-1α in primary human and L6 myotubes, while reducing the abundance of PDK1. In L6 myotubes treated with PYR-41, chloroquine increased the abundance of the epidermal growth factor receptor, but did not prevent the suppression of PDK1. Collectively, our results suggest that cultured myotubes degrade PDK1 via a pathway that cannot be inhibited by MG132, PYR-41, and/or chloroquine.

Greater molecular potential for glucose metabolism in adipose tissue and skeletal muscle of women compared with men.

Women typically have less muscle mass and more fat mass than men, while at the same time possessing similar or even greater whole-body insulin sensitivity. Our study aimed to investigate the molecular factors in primarily adipose tissue, but also in skeletal muscle, contributing to this sex difference. In healthy, moderately active premenopausal women and men with normal weight (28 ± 5 and 23 ± 3 years old; BMI 22.2 ± 1.9 and 23.7 ± 1.7) and in healthy, recreationally active women and men with overweight (32.2 ± 6 and 31.0 ± 5 years old; BMI 29.8 ± 4.3 & 30.9 ± 3.7) matched at age, BMI, and fitness level, we assessed insulin sensitivity and glucose tolerance with a hyperinsulinemic-euglycemic clamp or oral glucose tolerance test and studied subcutaneous adipose tissue and skeletal muscle samples with western blotting. Additionally, we traced glucose-stimulated glucose disposal in adipose tissues of female and male C57BL/6J littermate mice aged 16 weeks and measured glucose metabolic proteins. Our findings revealed greater protein expression related to glucose disposal in the subcutaneous adipose tissue (AKT2, insulin receptor, glucose transport 4) and skeletal muscle (hexokinase II, pyruvate dehydrogenase) in women compared to matched men with normal weight and with overweight. This increased protein capacity for glucose uptake extended to white adipose tissues of mice accompanied with ~2-fold greater glucose uptake compared to male mice. Furthermore, even in the obese state, women displayed better glucose tolerance than matched men, despite having 46% body fat and 20 kg less lean mass. In conclusion, our findings suggest that the superior potential for glucose disposal in female subcutaneous adipose tissue and skeletal muscle, driven by greater expression of various glucose metabolic proteins, compensates for their lower muscle mass. This likely explains women's superior glucose tolerance and tissue insulin sensitivity compared to men.

Insulin-Heart Axis: Bridging Physiology to Insulin Resistance.

Insulin signaling is vital for regulating cellular metabolism, growth, and survival pathways, particularly in tissues such as adipose, skeletal muscle, liver, and brain. Its role in the heart, however, is less well-explored. The heart, requiring significant ATP to fuel its contractile machinery, relies on insulin signaling to manage myocardial substrate supply and directly affect cardiac muscle metabolism. This review investigates the insulin-heart axis, focusing on insulin's multifaceted influence on cardiac function, from metabolic regulation to the development of physiological cardiac hypertrophy. A central theme of this review is the pathophysiology of insulin resistance and its profound implications for cardiac health. We discuss the intricate molecular mechanisms by which insulin signaling modulates glucose and fatty acid metabolism in cardiomyocytes, emphasizing its pivotal role in maintaining cardiac energy homeostasis. Insulin resistance disrupts these processes, leading to significant cardiac metabolic disturbances, autonomic dysfunction, subcellular signaling abnormalities, and activation of the renin-angiotensin-aldosterone system. These factors collectively contribute to the progression of diabetic cardiomyopathy and other cardiovascular diseases. Insulin resistance is linked to hypertrophy, fibrosis, diastolic dysfunction, and systolic heart failure, exacerbating the risk of coronary artery disease and heart failure. Understanding the insulin-heart axis is crucial for developing therapeutic strategies to mitigate the cardiovascular complications associated with insulin resistance and diabetes.

AMPK activation by dietary acadesine improves fillet texture in large yellow croaker (Larimichthys crocea) fed a linseed oil-based diet

The impacts of AMP-activated protein kinase (AMPK) activation by dietary acadesine (AICAR) on growth performance and muscle quality of large yellow croaker (Larimichthys crocea) fed a linseed oil-based diet (LO) were investigated by a 56-day feeding trial in this study. Fish (initial weight: 92.24 ± 0.30 g) were fed fish oil-based diet (FO), LO or LA (LO diet supplemented with 150 mg kg−1 AICAR) with three replicates of each treatment. Results indicated that weight gain rate and specific growth rate (SGR) were significantly decreased in the LO and LA groups than those of the fish fed FO, while the opposite was true for the feed conversion ratio. Moreover, the SGR of fish fed LA was significantly lower than that of the LO group. Dietary linseed oil and AICAR significantly lowered muscle eicosapentaenoic acid and docosahexaenoic acid contents. Furthermore, the LO group showed significantly lower fillet hardness, chewiness and pH, while higher lipid loss than those of the FO group. However, the FO and LA groups had similar fillet hardness, lipid loss and pH. Compared with the fish fed FO and LA, the LO group possessed significantly lower p-AMPK protein level and p-AMPK/AMPK ratio in muscle. The phosphorylation of TOR protein and the ratios of p-TOR/TOR and p-S6/S6 were significantly decreased in muscle of the LA group than those of the fish fed FO and LO. Meanwhile, totally replacing fish oil with linseed oil inhibited the AMPK/SIRT1/PGC-1α pathway, changed myofibre characteristics (e.g., density, diameter and type of myofibre) and raised the expression of genes or activity of enzyme related to anaerobic metabolism in fish muscle. Dietary AICAR activated AMPK/SIRT1/PGC-1α pathway, restored myofibre characteristics and promoted aerobic metabolism-related genes expression in muscle to some extent. In conclusion, total substitution of dietary fish oil with linseed oil reduced growth, feed utilization and nutritive value of large yellow croaker. And high level of dietary linseed oil induced softer texture and poorer liquid holding capacity (LHC) of muscle, which may be ascribed to the myofibre characteristics changed by linseed oil through depressing muscle AMPK/SIRT1/PGC-1α pathway. Inclusion of AICAR in a linseed oil-based diet improved fish muscle hardness and LHC, which may be relevant to the activated muscle AMPK/SIRT1/PGC-1α pathway and restored myofibre characteristics by AICAR. Notably, dietary AICAR could inhibit TOR pathway by activating AMPK in muscle, which may be responsible for the further decreased SGR of fish fed a linseed oil-based diet.

Genome to phenome Association for Pork Belly Parameters Elucidates Three Regulation Distinctions: Adipogenesis, muscle formation, and their transcription factors

Genome to phenome analysis is necessary in livestock areas because of its various and complex phenotypes. Pork belly is a favorable part of meat worldwide, including East Asia. A previous study has suggested that the three key transcription factors (ZNF444, NFYA and PPARG) affecting pork belly traits include total volume, the volume of total fat and muscle, and component muscles of the corresponding slice. However, other transcription factor genes affecting each slice other than pork belly component traits still needed to be identified. Thus, we aimed to analyze pork belly components at the genome to phenome level for identifying key transcription factor genes and their co-associated networks. The range of node numbers against each component trait via the association weight matrix was from 598 to 3020. Premised on the result, an in silico functional approach was performed. Each co-association network enriched three key transcription factors in adipogenesis and skeletal muscle proliferation, mesoderm development, metabolism, and gene transcription. The three key transcription factors and their related genes may be useful in comprehending their effect of pork belly construction.

Impact of Selected Glucagon-like Peptide-1 Receptor Agonists on Serum Lipids, Adipose Tissue, and Muscle Metabolism-A Narrative Review.

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.

The effects of the feeding duration of propylene glycol on major meat quality parameters and substantial proteins in the muscle of Akkaraman lambs

In this study, the effects of propylene glycol (PG) on meat quality and molecular pathways related to energy metabolism in longissimus lumborum muscle on lambs were evaluated. Seventy-two lambs were divided into three groups consisting of 60th, 90th, and 120th of slaughter days. The dosage of the PG and slaughter days were the variables used in the study. Eight animals were slaughtered from each group on each day. The meat quality parameters (e.g., pH, protein, fatty acid profile) and IGF-1, IGFBP4, and DGAT1 (i.e., mRNA and protein levels) were evaluated. The pH 45 min post-slaughter was higher in PG groups on 120th day. On the 4th day after slaughter, the b value was the lowest in the PG3, while 7th day after slaughter it was highest in Con and PG3 on 90th day. The total n3 and n6 were lowest and the NV was highest on 120th day. The IGFBP4 was upregulated in the PG groups on all of the slaughter days. The DGAT1 was upregulated in the PG3 on the 90th day. The IGF-1, DGAT1, IGFBP4 protein levels were found to have increased in the PG3 on 90th day. The IGFBP4 was found to have decreased in the PG3 on 120th day. According to the results of the study, the oral administration of the PG at the 3 mL/kg live weight0.75 for at least 120 days may have positive effects on meat quality in lambs through the IGF-1, DGAT1, and IGFBP4 genes and the proteins encoded by these genes.

Physical performance and plasma metabolic profile as potential prognostic factors in metastatic lung cancer patients.

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. 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. 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. 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.

Evaluation of the relationship between intercostal muscle oxygenation measured by near-infrared spectroscopy and exercise capacity in group E COPD patients

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.

A randomized translational study on protein- and glucose metabolism in skeletal muscles evaluated by gene-ontology, following preoperative oral carbohydrate loading compared to overnight peripheral parenteral nutrition (PPN) before major cancer surgery

BackgroundEffects of preoperative drinks on muscle metabolism are unclear despite general recommendations. The aim of the present study was therefore to compare metabolic effects of a preoperative oral nutrition drink, recommended by protocols for enhanced recovery after surgery (ERAS), compared to overnight preoperative peripheral total parenteral nutrition (PPN) on skeletal muscle metabolism in patients aimed at major gastrointestinal cancer surgery.MethodsPatients were randomized, based on diagnosis and clinical characteristics, to receive either a commercial carbohydrate-rich nutrition drink (Drink); or overnight (12 h) peripheral parenteral nutrition (PPN) as study regimens; compared to isotone Ringer-acetate as Control regimen. Arterial blood- and abdominal muscle tissue specimens were collected at start of surgery. Blood chemistry included substrate- and hormone concentrations. Muscle mRNA transcript analyses were performed by microarray and evaluated for changes in gene activities by Gene Ontology algorithms.ResultsPatient groups were comparable in all measured preoperative assessments. The Nutrition Drink had significant metabolic alterations on muscle glucose metabolism (p < 0.05), without any significant effects on amino acid- and protein metabolism. PPN showed similar significant effects on glucose metabolism as Drinks (p < 0.05), but indicated also major positive effects on amino acid- (p < 0.001) and protein anabolism (p < 0.05), particularly by inhibition of muscle protein degradation, related to both ubiquitination of proteins and autophagy/lysosome pathways (p < 0.05).ConclusionConventional overnight preoperative PPN seems effective to induce and support improved muscle protein metabolism in patients aimed at major cancer surgery while preoperative oral carbohydrate loading, according to ERAS-protocols, was ineffective to improve skeletal muscle catabolism and should therefore not be recommended before major cancer surgery.Trial registration Clinical trials.gov: NCT05080816, Registered June 10th 2021- Retrospectively registered. https://clinicaltrials.gov/study/NCT05080816

The effect of high-intensity interval training on type 2 diabetic muscle: A metabolomics-based study

BackgroundThis study aimed to investigate the effect of eight weeks of high-intensity interval training (HIIT) on muscle metabolism in rats with type 2 diabetes (T2D) using metabolomics approaches. Methods20 male Wistar rats at the age of 8 weeks-were assigned to four groups of five, each in the group randomly: control (CTL), type 2 diabetes (DB), HIIT (EX), and type 2 diabetes + HIIT (DBX). T2D was induced by two months of a high-fat diet plus a single dose of streptozotocin (35 mg/kg). Rats in the EX and DBX groups performed eight weeks of HIIT (running at 80–100 % of Vmax, 4–10 intervals). NMR spectroscopy was used to determine the changes in the muscle metabolome profile after training. ResultsChanges in metabolite abundance following exercise revealed distinct clustering in multivariate analysis. The essential metabolite changes between the DB and CTL groups were arginine metabolism, purine metabolism, phosphate pathway, amino sugar metabolism, glutathione metabolism, and aminoacyl-tRNA biosynthesis. However, Arginine biosynthesis, pyrimidine metabolism, aminoacyl-tRNA biosynthesis, and alanine, aspartate, and glutamate metabolism were altered between the DBX and DB groups. ConclusionThese results suggest that eight weeks of HIIT could reverse metabolic changes induced by T2D in rat muscles, contributing to reduced FBG and HOMA-IR levels.

Pleiotropic effects of an eQTL in the CELSR2/PSRC1/SORT1 cluster that associates with LDL-C and resting metabolic rate.

The locus CELSR2-PSRC1-SORT1, a primary genetic signal for lipids, has recently been implicated in different metabolic processes. Our investigation identified its association with energy metabolism. To determine biological mechanisms that govern diverse functions of this locus. Genotypes for 491,265 variants in 7,000 clinically characterized American Indians were previously determined using a custom-designed array specific for this longitudinally studied American Indian population. Among the genotyped individuals, 5,205 had measures of fasting lipid levels and 509 had measures of resting metabolic rate (RMR) and substrate oxidation rate assessed through indirect calorimetry. A genome-wide association study (GWAS) for LDL-C levels identified a variant in CELSR2 and the molecular impact of this variant on gene expression was assessed in skeletal muscle biopsies from 207 participants, followed by functional validation in mouse myoblasts using a luciferase assay. A GWAS in American Indians identified rs12740374 in CELSR2 as the top signal for LDL-C levels (P = 1 × 10-22); further analysis of this variant identified an unexpected correlation with reduced RMR (effect = -44.3 kcal/day/minor-allele) and carbohydrate oxidation rate (effect = -5.21 mg/hour/kg-EMBS). Tagged variants showed a distinct linkage disequilibrium architecture in American Indians, highlighting a potential functional variant, rs6670347 (minor-allele frequency = 0.20). Positioned in the glucocorticoid receptor's core binding motif, rs6670347 is part of a skeletal muscle-specific enhancer. Human skeletal muscle transcriptome analysis showed CELSR2 as the most differentially expressed gene (P = 1.9 × 10-7), with the RMR-lowering minor allele elevating gene expression. Experiments in mouse myoblasts confirmed enhancer-based regulation of CELSR2 expression, dependent on glucocorticoids. Rs6670347 also associated with increased oxidative phosphorylation gene expression; CELSR2 as a regulator of these genes, suggests potential influence on energy metabolism through muscle oxidative capacity. Variants in the CELSR2/PSRC1/SORT1 locus exhibit tissue-specific effects on metabolic traits, with an independent role in muscle metabolism through glucocorticoid signaling.

P38α MAPK Coordinates Mitochondrial Adaptation to Caloric Surplus in Skeletal Muscle.

Excessive calorie intake leads to mitochondrial overload and triggers metabolic inflexibility and insulin resistance. In this study, we examined how attenuated p38α activity affects glucose and fat metabolism in the skeletal muscles of mice on a high-fat diet (HFD). Mice exhibiting diminished p38α activity (referred to as p38αAF) gained more weight and displayed elevated serum insulin levels, as well as a compromised response in the insulin tolerance test, compared to the control mice. Additionally, their skeletal muscle tissue manifested impaired insulin signaling, leading to resistance in insulin-mediated glucose uptake. Examination of muscle metabolites in p38αAF mice revealed lower levels of glycolytic intermediates and decreased levels of acyl-carnitine metabolites, suggesting reduced glycolysis and β-oxidation compared to the controls. Additionally, muscles of p38αAF mice exhibited severe abnormalities in their mitochondria. Analysis of myotubes derived from p38αAF mice revealed reduced mitochondrial respiratory capacity relative to the myotubes of the control mice. Furthermore, these myotubes showed decreased expression of Acetyl CoA Carboxylase 2 (ACC2), leading to increased fatty acid oxidation and diminished inhibitory phosphorylation of pyruvate dehydrogenase (PDH), which resulted in elevated mitochondrial pyruvate oxidation. The expected consequence of reduced mitochondrial respiratory function and uncontrolled nutrient oxidation observed in p38αAF myotubes mitochondrial overload and metabolic inflexibility. This scenario explains the increased likelihood of insulin resistance development in the muscles of p38αAF mice compared to the control mice on a high-fat diet. In summary, within skeletal muscles, p38α assumes a crucial role in orchestrating the mitochondrial adaptation to caloric surplus by promoting mitochondrial biogenesis and regulating the selective oxidation of nutrients, thereby preventing mitochondrial overload, metabolic inflexibility, and insulin resistance.

Skeletal muscle p53-depletion uncovers a mechanism of fuel usage suppression that enables efficient energy conservation.

The ability of skeletal muscle to respond adequately to changes in nutrient availability, known as metabolic flexibility, is essential for the maintenance of metabolic health and loss of flexibility contributes to the development of diabetes and obesity. The tumour suppressor protein, p53, has been linked to the control of energy metabolism. We assessed its role in the acute control of nutrient allocation in skeletal muscle in the context of limited nutrient availability. A mouse model with inducible deletion of the p53-encoding gene, Trp53, in skeletal muscle was generated using the Cre-loxP-system. A detailed analysis of nutrient metabolism in mice with control and knockout genotypes was performed under ad libitum fed and fasting conditions and in exercised mice. Acute deletion of p53 in myofibres of mice activated catabolic nutrient usage pathways even under ad libitum fed conditions, resulting in significantly increased overall energy expenditure (+10.6%; P=0.0385) and a severe nutrient deficit in muscle characterized by depleted intramuscular glucose and glycogen levels (-62,0%; P<0.0001 and -52.7%; P<0.0001, respectively). This was accompanied by changes in marker gene expression patterns of circadian rhythmicity and hyperactivity (+57.4%; P=0.0068). These metabolic changes occurred acutely, within 2-3days after deletion of Trp53 was initiated, suggesting a rapid adaptive response to loss of p53, which resulted in a transient increase in lactate release to the circulation (+46.6%; P=0.0115) from non-exercised muscle as a result of elevated carbohydrate mobilization. Conversely, an impairment of proteostasis and amino acid metabolism was observed in knockout mice during fasting. During endurance exercise testing, mice with acute, muscle-specific Trp53 inactivation displayed an early exhaustion phenotype with a premature shift in fuel usage and reductions in multiple performance parameters, including a significantly reduced running time and distance (-13.8%; P=0.049 and -22.2%; P=0.0384, respectively). These findings suggest that efficient nutrient conservation is a key element of normal metabolic homeostasis that is sustained by p53. The homeostatic state in metabolic tissues is actively maintained to coordinate efficient energy conservation and metabolic flexibility towards nutrient stress. The acute deletion of Trp53 unlocks mechanisms that suppress the activity of nutrient catabolic pathways, causing substantial loss of intramuscular energy stores, which contributes to a fasting-like state in muscle tissue. Altogether, these findings uncover a novel function of p53 in the short-term regulation of nutrient metabolism in skeletal muscle and show that p53 serves to maintain metabolic homeostasis and efficient energy conservation.

Influences of Stocking Density on Antioxidant Status, Nutrients Composition, and Lipid Metabolism in the Muscles of Cyprinus carpio under Rice-Fish Co-Culture.

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.

Exploring Serotonin in Catch Contractions and Specific Dynamic Action in Postprandial Metabolism: Insights from Aquatic Models

Animal model organisms have long been instrumental in unraveling complex biological processes relevant to human physiology. The first study investigates how exercise and food intake affect metabolism, using zebrafish as our model. The second experiment dives into how neurotransmitters like dopamine and serotonin control muscle movements, particularly catch contractions, in mussels. Examining these processes provides insights into how muscle function and metabolism are regulated, potentially shedding light on human health and conservation efforts.

Non-Alcoholic Fatty Liver Disease Induced by Feeding Medium-Chain Fatty Acids Upregulates Cholesterol and Lipid Homeostatic Genes in Skeletal Muscle of Neonatal Pigs.

Non-alcoholic fatty liver disease (NAFLD) is a range of disorders characterized by lipid accumulation in hepatocytes. Although this spectrum of disorders is associated with adult obesity, recent evidence suggests that this condition could also occur independently of obesity, even in children. Previously, we reported that pigs fed a formula containing medium-chain fatty acids (MCFAs) developed hepatic steatosis and weighed less than those fed an isocaloric formula containing long-chain fatty acids (LCFAs). Our objective was to determine the association between NAFLD and the skeletal muscle transcriptome in response to energy and lipid intake. Neonatal pigs were fed one of three formulas: a control formula (CONT, n = 6) or one of two isocaloric high-energy formulas containing either long (LCFA, n = 6) or medium (MCFA, n = 6) chain fatty acids. Pigs were fed for 22 d, and tissues were collected. Body weight at 20 and 22 d was greater for LCFA-fed pigs than their CONT or MCFA counterparts (p < 0.005). Longissimus dorsi weight was greater for LCFA compared with MCFA, while CONT was intermediate (p < 0.05). Lean gain and protein deposition were greater for LCFA than for CONT and MCFA groups (p < 0.01). Transcriptomic analysis revealed 36 differentially expressed genes (DEGs) between MCFA and LCFA, 53 DEGs between MCFA and CONT, and 52 DEGs between LCFA and CONT (FDR < 0.2). Feeding formula high in MCFAs resulted in lower body and muscle weights. Transcriptomics data suggest that the reduction in growth was associated with a disruption in cholesterol metabolism in skeletal muscles.

The Role of Branched Chain Ketoacid Dehydrogenase Kinase (BCKDK) in Skeletal Muscle Biology and Pathogenesis.

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.

Serum dysregulation of serine and glycine metabolism as predictive biomarker for cognitive decline in frail elderly subjects

Frailty is a common age-related clinical syndrome characterized by a decline in the function of multiple organ systems, increased vulnerability to stressors, and a huge socio-economic burden. Despite recent research efforts, the physiopathological mechanisms underlying frailty remain elusive and biomarkers able to predate its occurrence in the early stages are still lacking. Beyond its physical component, cognitive decline represents a critical domain of frailty associated with higher risk of adverse health outcomes. We measured by High-Performance Liquid Chromatography (HPLC) a pool of serum amino acids including L-glutamate, L-aspartate, glycine, and D-serine, as well as their precursors L-glutamine, L-asparagine, and L-serine in a cohort of elderly subjects encompassing the entire continuum from fitness to frailty. These amino acids are known to orchestrate excitatory and inhibitory neurotransmission, and in turn, to play a key role as intermediates of energy homeostasis and in liver, kidney, muscle, and immune system metabolism. To comprehensively assess frailty, we employed both the Edmonton Frail Scale (EFS), as a practical tool to capture the multidimensionality of frailty, and the frailty phenotype, as a measure of physical function. We found that D-serine and D-/Total serine ratio were independent predictors of EFS but not of physical frailty. Furthermore, higher levels of glycine, glycine/L-serine and D-/Total serine were associated with worse cognition and depressive symptoms in the frail group. These findings suggest that changes in peripheral glycine and serine enantiomers homeostasis may represent a novel biochemical correlate of frailty.

Molecular signatures of longissimus dorsi differ between dairy cattle based on prepartum muscle reserves and branched-chain volatile fatty acid supplementation.

Dairy cattle with high (HM) versus low muscle (LM) reserves exhibit distinct temporal changes in longissimus dorsi muscle depth (LDD) in late gestation. Branched-chain volatile fatty acids (BCVFA) supplementation increased blood glucose levels. We hypothesized that differences in HM and LM reflect distinct muscle metabolism and BCVFA supplementation altered metabolic pathways. At 42 d before expected calving (BEC) Holstein dairy cows were enrolled in a 2 x 2 factorial study of diet and muscle reserves, by assigning 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 was biopsied at 21 d BEC, total RNA isolated and protein coding gene expression measured with RNA-seq. 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 and MYH2 greater in HM cattle (P<0.05). Signatures of LM cattle relative to HM 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 TCA cycle as acetyl CoA. Molecular signatures support distinct metabolic strategies between LM and HM cattle, and that BCVFA supplementation increased substrates for energy generation.