Search Results (9,486)

Deoxynivalenol (DON) is a common mycotoxin that causes immunosuppression in pigs. Its effects on cellular metabolism remain unclear. In this study, we investigate DON-induced metabolic alterations in porcine alveolar macrophage cell line 3D4/21 using non-targeted metabolomics. MTT assays showed DON reduced cell viability in a concentration- and time-dependent manner. Principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) revealed distinct metabolic profiles between control and DON-treated groups. Metabolomic analysis identified 127 differential metabolites (VIP > 1, p < 0.05), primarily in purine metabolism, glutathione metabolism, and arginine–proline metabolism. Integration with transcriptomic data confirmed that these pathways play key roles in DON-induced immunotoxicity. Specifically, changes in purine metabolism suggested disrupted nucleotide synthesis and energy balance, while glutathione depletion indicated weakened antioxidant defense. These findings provided a systems biology perspective on DON’s metabolic reprogramming of immune cells and identified potential therapeutic targets to reduce mycotoxin-related immunosuppression in swine. Full article

Speed is not only the primary objective of racehorse breeding but also a crucial indicator for evaluating racehorse performance. This study investigates a newly developed racehorse breed in China. Through whole-genome resequencing, we selected 60 offspring obtained from the crossbreeding of Thoroughbred horses and Xilingol horses for this study. This breed is tentatively named “Grassland-Thoroughbred”, and the samples were divided into two groups based on racing ability: 30 racehorses and 30 non-racehorses. Based on whole-genome sequencing data, the study achieved an average sequencing depth of 25.63×. The analysis revealed strong selection pressure on chromosomes (Chr) 1 and 3. Selection signals were detected using methods such as the nucleotide diversity ratio (π ratio), integrated haplotype score (iHS), fixation index (Fst), and cross-population extended haplotype homozygosity (XP-EHH). Regions ranked in the top 5% by at least three methods were designated as candidate regions. This approach detected 215 candidate genes. Additionally, the Fst method was employed to detect Indels, and the top 1% regions detected were considered candidate regions, covering 661 candidate genes. Functional enrichment analysis of the candidate genes suggests that pathways related to immune regulation, neural signal transmission, muscle contraction, and energy metabolism may significantly influence differences in performance. Among these identified genes, PPARGC1A, FOXO1, SGCD, FOXP2, PRKG1, SLC25A15, CKMT2, and TRAP1 play crucial roles in muscle function, metabolism, sensory perception, and neurobiology, indicating their key significance in shaping racehorse phenotypes. This study not only enhances understanding of the molecular mechanisms underlying racehorse speed but also provides essential theoretical and practical references for the molecular breeding of Grassland-Thoroughbreds. Full article

The increasing prevalence of chronic metabolic diseases poses a significant challenge in the modern world, impacting healthcare systems and individual life expectancy. The World Health Organization (WHO) recommends that older adults (65+ years) engage in 150–300 min of moderate-intensity or 75–150 min of vigorous-intensity physical activity, alongside muscle-strengthening and balance-training exercises at least twice a week. However, nearly one-third of the adult population (31%) is physically inactive, which increases the risk of developing obesity, type 2 diabetes, cardiovascular diseases, hypertension, and psychological issues. Physical activity in the form of aerobic exercise, resistance training, or a combination of both is effective in preventing and managing these metabolic diseases. In this review, we explored the effects of exercise training, especially on respiratory and pulmonary factors, including oxygen consumption, pulmonary ventilation, and blood gas analyses among adults. During exercise, oxygen consumption can increase up to 15-fold (from a resting rate of ~250 mL/min) to meet heightened metabolic demands, enhancing tidal volume and pulmonary efficiency. During exercise, the increased energy demand of skeletal muscle leads to increases in tidal volume and pulmonary function, while blood gases play a key role in maintaining the pH of the blood. In this review, we explored the influence of age, body composition (BMI and obesity), lifestyle factors (smoking and alcohol use), and comorbidities (diabetes, hypertension, neurodegenerative disorders) in the modulation of these physiological responses. We underscored exercise as a potent non-pharmacological intervention for improving cardiopulmonary health and mitigating the progression of metabolic diseases in aging populations. Full article

The core perturbome is defined as a central response to multiple disturbances, functioning as a complex molecular network to overcome the disruption of homeostasis under stress conditions, thereby promoting tolerance and survival under stress conditions. Based on the biological and clinical relevance of Escherichia coli and Staphylococcus aureus, we characterized their molecular responses to multiple perturbations. Gene expression data from E. coli (8815 target genes—based on a pangenome—across 132 samples) and S. aureus (3312 target genes across 156 samples) were used. Accordingly, this study aimed to identify and describe the functionality of the core perturbome of these two prokaryotic models using a machine learning approach. For this purpose, feature selection and classification algorithms (KNN, RF and SVM) were implemented to identify a subset of genes as core molecular signatures, distinguishing control and perturbation conditions. After verifying effective dimensional reduction (with median accuracies of 82.6% and 85.1% for E. coli and S. aureus, respectively), a model of molecular interactions and functional enrichment analyses was performed to characterize the selected genes. The core perturbome was composed of 55 genes (including nine hubs) for E. coli and 46 (eight hubs) for S. aureus. Well-defined interactomes were predicted for each model, which are jointly associated with enriched pathways, including energy and macromolecule metabolism, DNA/RNA and protein synthesis and degradation, transcription regulation, virulence factors, and other signaling processes. Taken together, these results may support the identification of potential therapeutic targets and biomarkers of stress responses in future studies. Full article

Macrobrachium nipponense represents a commercial decapod species that predominantly inhabits freshwater ecosystems or environments with low salinity. However, the species exhibits normal survival and reproductive capacity in natural aquatic habitats with salinity levels up to 10 parts per thousand (ppt). The present study aimed to elucidate the molecular mechanisms underlying salinity acclimation in M. nipponense by investigating alterations in oxidative stress, morphological adaptations, and hepatopancreatic gene expression profiles following exposure to a salinity level of 10 ppt. The present study demonstrates that glutathione peroxidase and Na⁺/K⁺-ATPase play critical roles in mitigating oxidative stress induced by elevated salinity in M. nipponense. Furthermore, histological analysis revealed distinct pathological alterations in the hepatopancreas of M. nipponense following 7-day salinity exposure, including basement-membrane disruption, luminal expansion, vacuolization, and a marked reduction in storage cells. Transcriptomic profiling of M. nipponense hepatopancreas suggested coordinated activation of both immune (lysosome and protein processing in endoplasmic reticulum pathways) and energy (pyruvate metabolism, glycolysis/gluconeogenesis, and citrate cycle) metabolic processes during salinity acclimation in M. nipponense. Quantitative real-time PCR validation confirmed the reliability of RNA-seq data. This study provides molecular insights into the salinity adaptation mechanisms in M. nipponense, offering potential applications for improving cultivation practices in brackish water environments. Full article

Circadian rhythms are intrinsic 24 h cycles that regulate metabolic processes across multiple tissues, with skeletal muscle emerging as a central node in this temporal network. Muscle clocks govern gene expression, fuel utilisation, mitochondrial function, and insulin sensitivity, thereby maintaining systemic energy homeostasis. However, circadian misalignment, whether due to behavioural disruption, nutrient excess, or metabolic disease, impairs these rhythms and contributes to insulin resistance, and the development of obesity, and type 2 diabetes mellitus. Notably, the muscle clock remains responsive to non-photic cues, particularly exercise, which can reset and amplify circadian rhythms even in metabolically impaired states. This work synthesises multi-level evidence from rodent models, human trials, and in vitro studies to elucidate the role of skeletal muscle clocks in circadian metabolic health. It explores how exercise entrains the muscle clock via molecular pathways involving AMPK, SIRT1, and PGC-1α, and highlights the time-of-day dependency of these effects. Emerging data demonstrate that optimally timed exercise enhances glucose uptake, mitochondrial biogenesis, and circadian gene expression more effectively than time-agnostic training, especially in individuals with metabolic dysfunction. Finally, findings are integrated from multi-omic approaches that have uncovered dynamic, time-dependent molecular signatures that underpin circadian regulation and its disruption in obesity. These technologies are uncovering biomarkers and signalling nodes that may inform personalised, temporally targeted interventions. By combining mechanistic insights with translational implications, this review positions skeletal muscle clocks as both regulators and therapeutic targets in metabolic disease. It offers a conceptual framework for chrono-exercise strategies and highlights the promise of multi-omics in developing precision chrono-medicine approaches aimed at restoring circadian alignment and improving metabolic health outcomes. Full article

Background: Exercise-induced fatigue arises primarily from energy substrate depletion and the accumulation of metabolites such as lactate and ammonia, which impair performance and delay recovery. Emerging evidence implicates gut microbiota modulation—particularly via probiotics—as a means to optimize host energy metabolism and accelerate clearance of fatigue-associated by-products. Objective: This study aimed to determine whether live or heat-inactivated Lacticaseibacillus paracasei NB23 can enhance exercise endurance and attenuate fatigue biomarkers in a murine model. Methods: Forty male Institute of Cancer Research (ICR) mice were randomized into four groups (n = 10 each) receiving daily gavage for six weeks with vehicle, heat-killed NB23 (3 × 10¹⁰ cells/mouse/day), low-dose live NB23 (1 × 10¹⁰ CFU/mouse/day), or high-dose live NB23 (3 × 10¹⁰ CFU/mouse/day). Forelimb grip strength and weight-loaded swim-to-exhaustion tests assessed performance. Blood was collected post-exercise to measure serum lactate, ammonia, blood urea nitrogen (BUN), and creatine kinase (CK). Liver and muscle glycogen content was also quantified, and safety was confirmed by clinical-chemistry panels and histological examination. Results: NB23 treatment produced dose-dependent improvements in grip strength (p < 0.01) and swim endurance (p < 0.001). All NB23 groups exhibited significant reductions in post-exercise lactate (p < 0.0001), ammonia (p < 0.001), BUN (p < 0.001), and CK (p < 0.0001). Hepatic and muscle glycogen stores rose by 41–59% and 65–142%, respectively (p < 0.001). No changes in food or water intake, serum clinical-chemistry parameters, or tissue histology were observed. Conclusions: Our findings suggest that both live and heat-treated L. paracasei NB23 may contribute to improved endurance performance, increased energy reserves, and faster clearance of fatigue-related metabolites in our experimental model. However, these results should be interpreted cautiously given the exploratory nature and limitations of our study. Full article

Anaerobic digestion (AD) is a sustainable and widely adopted technology for the treatment of organic solid wastes (OSWs). However, AD efficiency varies significantly across different substrates, primarily due to differences in the microbial community and metabolic pathways. This review provides a comprehensive summary of the AD processes for four types of typical OSWs (i.e., sewage sludge, food waste, livestock manure, and straw), with an emphasis on their universal characteristics across global contexts, focusing mainly on the electron transfer mechanisms, essential microbial communities, and key metabolic pathways. Special attention was given to the mechanisms by which substrate-specific structural differences influence anaerobic digestion efficiency, with a focused analysis and discussion on how different components affect microbial communities and metabolic pathways. This study concluded that the hydrogenotrophic methanogenesis pathway, TCA cycle, and the Wood–Ljungdahl pathway serve as critical breakthrough points for enhancing methane production potential. This research not only provides a theoretical foundation for optimizing AD efficiency, but also offers crucial scientific insights for resource recovery and energy utilization of OSWs, making significant contributions to advancing sustainable waste management practices. Full article

Skin aging is closely related to mitochondrial dysfunction and cell cycle abnormalities, and developing intervention strategies targeting mitochondrial quality control is an important direction for anti-aging research. In this study, we investigated the anti-aging mechanism of Camellia japonica flower (CJF) extract and its active ingredient hyperoside based on a doxorubicin (DOX)-induced endogenous senescence model in human skin fibroblasts (HSFs). LC-MS proteomics analysis revealed that CJF extract and hyperoside specifically activated the FUNDC1-mediated mitochondrial autophagy pathway, significantly ameliorated the DOX-induced decrease in mitochondrial membrane potential and the accumulation of reactive oxygen species (ROS), and alleviated the cellular S-phase blockade and reversed the high expression of senescence-associated β-galactosidase (SA-β-gal). Further studies showed that the two cleared damaged mitochondria by enhancing mitochondrial autophagy and restoring cellular energy metabolism homeostasis while promoting type III collagen and elastin synthesis and repairing the expression of Claudin 1 related to skin barrier function. For the first time, the present study reveals the molecular mechanism of CJF extract in delaying skin aging by regulating the FUNDC1-dependent mitochondrial autophagy pathway, which provides a theoretical basis and a candidate strategy for developing novel anti-aging agents targeting mitochondrial quality control. Full article

Background: Dietary advice for Paralympic athletes (PAs) with a spinal cord injury (PAs-SCI) requires particular attention and has been widely studied. However, currently, no particular attention has been addressed to nutritional guidelines for athletes with an amputation (PAs-AMP). This study aimed at filling up this gap, at least partially, and compared veteran PAs-SCI with PAs-AMP. Methods: A sample of 25 male PAs (12 with SCI and 13 with AMP), recruited during two training camps, was submitted to the following questionnaires: allergy questionnaire for athletes (AQUA), Nordic Musculoskeletal Questionnaire (NMQ), Starvation Symptom Inventory (SSI), neurogenic bowel dysfunction (NBD), orthorexia (ORTO-15/ORTO-7), alcohol use disorders identification test (AUDIT), and Mediterranean diet adherence (MDS). The PAs were also submitted to the following measurements: dietary Oxygen Radical Absorbance Capacity (ORAC) and intakes, body composition, handgrip strength (HGS), basal energy expenditure (BEE), peak oxygen uptake (VO_2peak), peak power, peak heart rate (HR), post-exercise ketosis, and antioxidant response after a cardiopulmonary exercise test (CPET) to voluntary fatigue. Results: Compared to PAs-AMP, PAs-SCI had higher NBD and lower VO_2peak (p < 0.05), peak power, peak HR, peak lactate, phase angle (PhA) of the dominant leg (p < 0.05), and ORTO15 (p < 0.05). The latter was related to NBD (r = −0.453), MDS (r = −0.638), and ORAC (r = −0.529), whereas ORTO7 correlated with PhA of the dominant leg (r = 0.485). Significant differences between PAs-AMP and PAs-SCI were not found in the antioxidant response, glucose, and ketone levels after CPET, nor in dietary intake, AUDIT, AQUA, NMQ, SSI, BEE, HGS, and FM%. Conclusions: The present study showed that PAs-SCI and PAs-AMP display similar characteristics in relation to lifestyle, energy intake, basal energy expenditure, and metabolic response to CPET. Based on both the similarities with PAs-SCI and the consequences of the limb deficiency impairment, PAs-AMP and PAs-SCI require personalized nutritional advice. Full article

Skeletal muscle atrophy is a critical health issue affecting the quality of life of elderly individuals and patients with chronic diseases. These conditions induce dysregulation of glucocorticoid (GC) secretion. GCs play a critical role in maintaining homeostasis in the stress response and glucose metabolism. However, prolonged exposure to GC is directly linked to muscle atrophy, which is characterized by a reduction in muscle size and weight, particularly affecting fast-twitch muscle fibers. The GC-activated glucocorticoid receptor (GR) decreases protein synthesis and facilitates protein breakdown. Numerous antagonists have been developed to mitigate GC-induced muscle atrophy, including 11β-HSD1 inhibitors and myostatin and activin receptor blockers. However, the clinical trial results have fallen short of the expected efficacy. Recently, several emerging pathways and targets have been identified. For instance, GC-induced sirtuin 6 isoform (SIRT6) expression suppresses AKT/mTORC1 signaling. Lysine-specific demethylase 1 (LSD1) cooperates with the GR for the transcription of atrogenes. The kynurenine pathway and indoleamine 2,3-dioxygenase 1 (IDO-1) also play crucial roles in protein synthesis and energy production in skeletal muscle. Therefore, a deeper understanding of the complexities of GR transactivation and transrepression will provide new strategies for the discovery of novel drugs to overcome the detrimental effects of GCs on muscle tissues. Full article

The relationship between metabolic dysfunction and mental health disorders is complex and has received increasing attention. This review integrates current research to explore how stress-related growth differentiation factor 15 (GDF15) signaling, ceramides derived from gut microbiota, and mitochondrial dysfunction in the brain interact to influence both metabolic and psychiatric conditions. Evidence suggests that these pathways converge to regulate brain energy homeostasis through feedback mechanisms involving the autonomic nervous system and the hypothalamic–pituitary–adrenal axis. GDF15 emerges as a key stress-responsive biomarker that links peripheral metabolism with brainstem GDNF family receptor alpha-like (GFRAL)-mediated anxiety circuits. Meanwhile, ceramides impair hippocampal mitochondrial function via membrane incorporation and disruption of the respiratory chain. These disruptions may contribute to sustained pathological states such as depression, anxiety, and cognitive dysfunction. Although direct mechanistic data are limited, integrating these pathways provides a conceptual framework for understanding metabolic–psychiatric comorbidities. Furthermore, differences in age, sex, and genetics may influence these systems, highlighting the need for personalized interventions. Targeting mitochondrial function, GDF15-GFRAL signaling, and gut microbiota composition may offer new therapeutic strategies. This integrative perspective helps conceptualize how metabolic and psychiatric mechanisms interact for understanding the pathophysiology of metabolic and psychiatric comorbidities and highlights therapeutic targets for precision medicine. Full article

Fyn is widely involved in diverse cellular physiological processes, including cell growth and survival, and has been implicated in the regulation of energy metabolism and the pathogenesis of diabetes mellitus through multiple pathways. Fyn plays a role in increasing fat accumulation and promoting insulin resistance, and it also contributes to the development of diabetic complications such as diabetic kidney disease and diabetic retinopathy. The primary mechanism by which Fyn modulates lipid metabolism is that it inhibits AMP-activated protein kinase (AMPK). Additionally, it affects energy homeostasis through regulating specific signal pathways affecting lipid metabolism including pathways related to CD36, through enhancement of adipocyte differentiation, and through modulating insulin signal transduction. Inflammatory stress is one of the fundamental mechanisms in diabetes mellitus and its complications. Fyn also plays a role in inflammatory stress-related signaling cascades such as the Akt/GSK-3β/Fyn/Nrf2 pathway, exacerbating inflammation in diabetes mellitus. Therefore, Fyn emerges as a promising therapeutic target for regulating glucolipid metabolism and alleviating type 2 diabetes mellitus. This review synthesizes research on the role of Fyn in the regulation of energy metabolism and the development of diabetes mellitus, while exploring its specific regulatory mechanisms. Full article

Diabetes mellites (DM) is a chronic disease with increasing prevalence worldwide and multiple health implications. Among them, sarcopenia is a metabolic disorder characterized by loss of muscle mass and function. The two age-related diseases, DM and sarcopenia, share underlying pathophysiological pathways. This narrative literature review aims to provide an overview of the existing evidence on metabolomic studies evaluating DM associated with sarcopenia. Advancements in targeted and untargeted metabolomics techniques could provide better insight into the pathogenesis of sarcopenia in DM and describe their entangled and fluctuating interrelationship. Recent evidence showed that sarcopenia in DM induced significant changes in protein, lipid, carbohydrate, and in energy metabolisms in humans, animal models of DM, and cell cultures. Newer metabolites were reported, known metabolites were also found significantly modified, while few amino acids and lipids displayed a dual behavior. In addition, several therapeutic approaches proved to be promising interventions for slowing the progression of sarcopenia in DM, including physical activity, newer antihyperglycemic classes, D-pinitol, and genetic USP21 ablation, although none of them were yet validated for clinical use. Conversely, ceramides had a negative impact. Further research is needed to confirm the utility of these findings and to provide potential metabolomic biomarkers that might be relevant for the pathogenesis and treatment of sarcopenia in DM. Full article

Background/Objectives: Neuromedin U (NMU) is a highly conserved gene encoding a neuropeptide involved in the regulation of feeding behavior and energy homeostasis. We aimed to analyze the association between NMU genetic and epigenetic variations and cardio-metabolic parameters in an Italian population to identify the role of these variants in cardio-metabolic risk. Methods: A total of 4028 subjects were randomly selected from the Moli-sani study cohort. NMU haplotypes were estimated using seven SNPs located in the gene body and in the promoter region; DNA methylation levels in the promoter region, previously associated with lipid-related variables in the same population, were also used. Results: Among the haplotypes inferred, the haplotype carrying the highest number of minor variants (frequency 16.6%), when compared with the most frequent haplotype, was positively associated with insulin levels, HOMA-IR, and diastolic blood pressure, and negatively with HDL-cholesterol. The multivariable analysis that considered methylation levels along with their interactions with SNPs showed that increased methylation levels in two close CpG sites were associated with higher levels of lipid-related variables. Conclusions: This study supports a role for NMU as a regulator of human metabolism. This finding suggests that NMU could be a potential target for preventive interventions against coronary and cerebrovascular diseases, and that NMU genetic and epigenetic variability may serve as a biomarker for cardio-metabolic risk. Full article