Search Results (10,426)

Background: Honeybees sustain vital ecological roles through foraging behavior, which provides pollination services and is likely regulated by dopamine signaling coupled to brain energy metabolism. However, the genetic and metabolic mechanisms underlying this regulation remain unclear. Methods: We treated honeybee workers with the dopamine receptor agonist bromocriptine and employed an integrative approach, combining liquid chromatography–mass spectrometry (LC–MS) metabolomics with single-nucleus RNA sequencing (snRNA-seq). Results: Metabolomics revealed increased levels of N6-carboxymethyllysine (CML) and a coordinated shift in central carbon metabolites, including higher glucose, pyruvate, and lactate within glycolysis, and ribose-5-phosphate in the pentose phosphate pathway (PPP). Integration with transcriptomics showed heterogeneous responses: glial cells exhibited higher glycolysis pathway scores and upregulated hexokinase expression compared to neurons, whereas major PPP enzymes were upregulated in both glial and neuronal subsets. Conclusions: These findings suggest that dopamine receptor activation is associated with altered whole-brain metabolic profiles and concurrent, cell-type-specific upregulation of glycolytic and PPP enzyme genes, particularly in glia. This study characterizes these neuro-metabolic associations, offering insights into the cellular and metabolic basis of foraging behavior in worker bees. Full article

Broodstock nutrition is a key determinant of reproductive output in marine fishes because lipids support yolk formation, embryonic development, and early larval viability. However, the allocation of lipid classes between fertilized eggs and the egg envelope (chorion) remains poorly characterized for many tropical species. In this study, we performed a comparative lipidomic analysis of dechorionated fertilized egg contents and isolated chorion from three tropical marine fishes (Trachinotus ovatus, Platax teira, and Plectropomus leopardus) using UHPLC–Q Exactive Orbitrap MS/MS. Multivariate analyses revealed clear tissue- and species-specific lipid patterns. Dechorionated eggs were enriched in energy-storage lipids, dominated by triacylglycerols and essential polyunsaturated fatty acids, whereas chorion tissues contained higher levels of structural and signaling lipids, including phosphatidylinositols and sphingolipids. Each species exhibited a distinct lipid signature, with T. ovatus characterized by higher secosteroids and free fatty acids, P. teira by glycerophosphoethanolamines and phosphoinositols, and P. leopardus by abundant triradylglycerols. Pathway enrichment highlighted glycerophospholipid metabolism and sphingolipid signaling as prominent processes during early development. These findings clarify lipid partitioning between dechorionated fertilized egg contents and the chorion and provide a biochemical rationale for optimizing species-specific broodstock diets to enhance egg quality in tropical marine aquaculture. Full article

Background/Objectives. Lactiplantibacillus plantarum CRL681 has previously demonstrated a strong antagonistic effect against Escherichia coli O157:H7 in food matrices; however, the molecular mechanisms underlying this activity remain poorly understood. Since initial interactions between beneficial bacteria and pathogens occur mainly at the cell surface and in the extracellular environment, the characterization of the bacterial secretome is essential for elucidating these mechanisms. In this study, the secretome of L. plantarum CRL681 was comprehensively characterized using an integrated in silico and in vitro approach. Methods. The exoproteome and surfaceome were analyzed by LC-MS/MS under pure culture conditions and during co-culture with E. coli O157:H7. Identified proteins were functionally annotated, classified according to subcellular localization and secretion pathways, and evaluated through protein–protein interaction network analysis. Results. A total of 275 proteins were proposed as components of the CRL681 secretome, including proteins involved in cell surface remodeling, metabolism and nutrient transport, stress response, adhesion, and genetic information processing. Co-culture with EHEC induced significant changes in the expression of proteins associated with energy metabolism, transport systems, and redox homeostasis, indicating a metabolic and physiological adaptation of L. plantarum CRL681 under competitive conditions. Notably, several peptidoglycan hydrolases, ribosomal proteins with reported antimicrobial activity, and moonlighting proteins related to adhesion were identified. Conclusions. Overall, these findings suggest that the antagonistic activity of L. plantarum CRL681 against E. coli O157:H7 would be mediated by synergistic mechanisms involving metabolic adaptation, stress resistance, surface adhesion, and the production of non-bacteriocin antimicrobial proteins, supporting its potential application as a bioprotective and functional probiotic strain. Full article

The progression of neoplastic diseases is driven by a complex interplay of biological processes, including uncontrolled proliferation, enhanced invasion, metastasis, and profound metabolic reprogramming. Among the hallmarks of cancer, as revised by Hanahan and Weinberg, the reprogramming of energy metabolism has emerged as a critical feature that enables cancer cells to meet their heightened bioenergetic and biosynthetic demands. One significant aspect of this metabolic adaptation is the accumulation of lipid droplets (LDs) dynamic, cytoplasmic organelles primarily involved in lipid storage and metabolic regulation. LDs serve as reservoirs of neutral lipids and play a multifaceted role in cancer cell physiology. Their accumulation is increasingly recognized as a marker of tumor aggressiveness and poor prognosis. By storing lipids, LDs provide a readily accessible source of energy and essential building blocks for membrane synthesis, supporting rapid cell division and growth. Moreover, LDs contribute to cellular homeostasis by modulating oxidative stress, maintaining redox balance, and regulating autophagy, particularly under nutrient-deprived or hypoxic conditions commonly found in the tumor microenvironment. Importantly, LDs have been implicated in the development of resistance to cancer therapies. They protect cancer cells from the cytotoxic effects of chemotherapeutic agents by buffering endoplasmic reticulum (ER) stress, inhibiting apoptosis, and facilitating survival pathways. The presence of LDs has been shown to correlate with increased resistance to a variety of chemotherapeutic drugs, although the precise molecular mechanisms underlying this phenomenon remain incompletely understood. Emerging evidence suggests that chemotherapy itself can induce changes in LD accumulation, further complicating treatment outcomes. Given their central role in cancer metabolism and therapy resistance, LDs represent a promising target for therapeutic intervention. Strategies aimed at disrupting lipid metabolism or inhibiting LD biogenesis have shown potential in sensitizing cancer cells to chemotherapy and overcoming drug resistance. In this review, we comprehensively examine the current understanding of LD biology in cancer, highlight studies that elucidate the link between LDs and drug resistance, and discuss emerging approaches to target lipid metabolic pathways to enhance therapeutic efficacy across diverse cancer types. Full article

Type 2 Diabetes Mellitus (T2DM) is a recognized risk factor for Alzheimer’s Disease (AD), as epidemiological research indicates that those with T2DM have a markedly increased risk of experiencing cognitive decline and dementia. Chronic hyperglycemia and insulin resistance in T2DM hinder cerebral glucose metabolism, reducing the primary energy source for neurons and compromising synaptic function. Insulin resistance impairs signaling pathways crucial for neuronal survival and plasticity, while high insulin levels compete with amyloid-β (Aβ) for breakdown by insulin-degrading enzyme, promoting Aβ buildup. Additionally, vascular issues linked to T2DM impair blood–brain barrier functionality, decrease cerebral blood flow, and worsen neuroinflammation. Elevated oxidative stress and advanced glycation end-products (AGEs) in diabetes exacerbate tau hyperphosphorylation and mitochondrial dysfunction, worsening neurodegeneration. Collectively, these processes create a robust biological connection between T2DM and AD, emphasizing the significance of metabolic regulation as a possible treatment approach for preventing or reducing cognitive decline. Here, we review the relationship between T2DM and AD and discuss the roles insulin, hyperglycemia, and inflammation therapeutic strategies have in successful development of AD therapies. Additionally evaluated are recent therapeutic advances, especially involving the polyflavonoid anthocyanin, against T2DM-mediated AD pathology. Full article

Gut microbiota has emerged as a modulator of host metabolism and energy balance. However, the precise microbial metabolites mediating thermogenic activation in obesity remain largely undefined. We investigated the effect of antibiotic treatment under a high-fat diet on metabolites and its contribution to lipolysis and thermogenesis. Antibiotic treatment in high-fat diet-fed rats reduced adiposity and enhanced adaptive thermogenesis. Metabolomics revealed elevated taurine levels in the cecum content and plasma of antibiotic-treated animals, correlating with increased expressions of UCP1 and TGR5 in brown adipose tissue. Taurine enhanced lipolysis and oxygen consumption in mouse adipose tissue and human adipocytes. Thereby, taurine modulated lipolysis dependent on TGR5 signaling in adipose tissue. Human data confirmed that taurine promotes browning of white adipocytes and that acute cold exposure leads to a marked drop in circulating taurine, suggesting its rapid recruitment into thermogenic tissues. Besides its synthesis in the liver and dietary uptake, taurine can be a microbiota-derived metabolite that activates adipose thermogenesis and lipolysis through TGR5 and possibly taurine transporter-dependent mechanisms. These findings uncover a gut–adipose axis with therapeutic potential for metabolic disease. Full article

Biofuel cells (BFCs) generate electricity by converting chemical energy into electrical energy using biological systems. Saccharomyces cerevisiae (yeast) is an attractive biocatalyst for BFCs due to its robustness, low cost, and metabolic versatility; however, electron transfer from the intracellular reactions to the electrode is limited by the cell membrane. Nystatin is an antifungal antibiotic that increases the permeability of fungal membranes. We hypothesized that sub-lethal nystatin treatment could enhance mediator-assisted electron transfer without compromising cell viability. In this work, yeast was treated with nystatin during cultivation at concentrations of up to 6 µg/mL and combined with a dual-mediator system consisting of a lipophilic mediator (9,10-phenanthrenequinone, PQ) and a hydrophilic mediator (potassium ferricyanide). Scanning electrochemical microscopy revealed that the dual-mediator system increased local current responses by approximately fivefold compared to a single mediator (from ~11 pA to ~59 pA), and that nystatin-treated yeast exhibited higher local electrochemical activity than untreated yeast (maximum currents of ~0.476 nA versus ~0.303 nA). Microbial fuel cell measurements showed that nystatin treatment increased the maximum power density from approximately 0.58 mW/m² to approximately 0.62 mW/m² under identical conditions. Nystatin concentrations between 4 and 5 µg/mL maintain yeast viability at near-control levels, while higher concentrations cause a decrease in viability. These results demonstrate that controlled, sub-lethal membrane permeabilization combined with a dual-mediator strategy can enhance electron transfer in yeast-based biofuel cells. Full article

Tibetan sheep, a unique breed indigenous to the Qinghai–Tibet Plateau, exhibit remarkable adaptations to high-altitude hypoxia, and their muscle quality is a key economic determinant. However, the molecular mechanisms by which exercise regulates meat quality in this breed remain poorly understood. This study aimed to systematically investigate the effects of different exercise volumes on the biceps femoris muscle of Tibetan sheep, integrating histological analysis with high-throughput transcriptome sequencing. We compared a low-exercise group with a high-exercise group and found that long-term endurance exercise resulted in phenotypic changes suggestive of a shift toward oxidative muscle fiber characteristics. This adaptation was characterized by significantly reduced muscle fiber diameter and cross-sectional area, alongside a crucial increase in intramuscular fat content, collectively enhancing meat tenderness, flavor, and juiciness. Transcriptomic analysis revealed extensive gene expression reprogramming, identifying 208 mRNAs and 490 lncRNAs that were differentially expressed and primarily associated with muscle fiber transition and energy metabolism. Furthermore, we constructed a putative lncRNA-miRNA-mRNA competing endogenous RNA network based on expression correlations and bioinformatic predictions, highlighting potential key regulatory axes such as LOC105603384/miR-16-z/MYLK3, LOC121820630/miR-381-y/NOX4, and LOC132659150/oar-miR-329a-3p/NF1. These findings provide a new perspective on the molecular basis of exercise-induced muscle adaptation in high-altitude animals and offer a solid theoretical framework for improving meat quality through scientific livestock management. Full article

Background/Objectives: Osteoporosis is a multifactorial skeletal disorder in which chronic inflammation, dysregulated cytokine signaling, and metabolic imbalance contribute to excessive bone resorption and impaired bone formation. Asiatic acid has demonstrated bone-protective effects, but its molecular mechanisms in osteoporosis remain incompletely understood. This study aimed to investigate the anti-osteoporotic mechanisms of asiatic acid using an integrative in silico strategy. Methods: Network pharmacology analysis was performed to identify osteoporosis-related molecular targets of asiatic acid. Molecular docking was used to predict the binding modes and affinities between asiatic acid and its target proteins. Molecular dynamics simulation was used to assess the structural stability and interaction persistence of the asiatic acid–protein complex. Results: Network pharmacology identified 135 overlapping targets between asiatic acid and osteoporosis, with IL-6, STAT3, PPARG, and NFKB1 emerging as key hubs. KEGG analysis indicated the PPAR signaling pathway as a potential mechanism underlying the anti-osteoporotic effect. Molecular docking showed strong binding energies of asiatic acid with all predicted target proteins, with the highest affinity observed for IL-6, involving key residues ASN61, LEU62, GLU172, LYS66, and ARG168. Consistently, molecular dynamics simulation confirmed stable binding of asiatic acid to IL-6, with persistent interactions with ASN61, LYS66, LEU62, LEU64, and GLN154 mediated by hydrogen bonds, water bridges, and hydrophobic interactions. Conclusions: This integrative in silico study provides mechanistic insight into the potential anti-osteoporotic actions of asiatic acid, implicating IL-6 as a plausible upstream molecular target. These results establish a robust mechanistic framework for future translational studies exploring asiatic acid as a natural therapeutic candidate for osteoporosis. Full article

Pasture-based ruminant systems link nitrogen (N) nutrition with ecosystem N cycling. Grazing ruminants convert fibrous forages into milk and meat but excrete 65 to 80% of ingested N, creating excreta hotspots that drive ammonia volatilization, nitrate leaching, and nitrous oxide (N₂O) emissions. This review synthesizes ecological and ruminant nutrition evidence on N flows, emphasizing microbial processes, biological N₂ fixation, plant diversity, and urine patch biogeochemistry, and evaluates strategies to improve N use efficiency (NUE). We examine rumen N metabolism in relation to microbial protein synthesis, urea recycling, and dietary factors including crude protein concentration, energy supply, forage composition, and plant secondary compounds that modulate protein degradability and microbial N capture, thereby influencing N partitioning among animal products, urine, and feces, as reflected in milk and blood urea N. We also examine how grazing patterns and excreta distribution, assessed with sensor technologies, modify N flows. Evidence indicates that integrated management combining dietary manipulation, forage diversity, targeted grazing, and decision tools can increase farm-gate NUE from 20–25% to over 30% while sustaining performance. Framing these processes within the global N cycle positions pasture-based ruminant systems as critical leverage points for aligning ruminant production with environmental and climate sustainability goals. Full article

Somatic embryogenesis (SE) plays a pivotal role in the propagation and genetic improvement of coniferous trees; however, its efficiency is frequently limited by the reduced embryogenic potential of callus cultures. Here, we investigated the metabolic determinants underlying this phenomenon in Picea mongolica by conducting a comparative metabolomic analysis of embryogenic calli (EC) and non-embryogenic calli (NEC). We observed significant metabolic differences between EC and NEC using an integrated approach combining morphological observations and untargeted liquid chromatography-tandem mass spectrometry (LC-MS/MS)-based metabolomics. EC exhibited increased central carbon metabolism, characterized by enhanced citrate cycle (TCA) flux, with significantly increased levels of the key TCA intermediates, citric acid and L-malic acid—18.8- and 3.6-fold higher, respectively, than those in NEC. Conversely, NEC displayed a divergent metabolic state, characterized by the accumulation of various amino acids and the activation of secondary metabolic pathways, especially alkaloid biosynthesis. These results indicate that embryogenic competence in P. mongolica is supported by a distinct metabolic program that prioritizes energy generation and efficient carbon-nitrogen allocation for biosynthetic processes. Conversely, the non-embryogenic state arises from a shift in metabolic resources toward secondary metabolism. These findings provide key metabolic insights and a theoretical basis for enhancing conifer SE systems. Full article

Light plays a critical role in the physiology and pigmentation of aquatic animals. Regulating the light environment of aquatic animals offers insights into healthy aquaculture practices. In this study, Procambarus clarkii were reared under four different light colors—white (WL), red (RL), blue (BL), and green (GL)—for 21 days, with four replicates per light color. Morphological characteristics did not differ among light treatments. However, significant differences were observed in hemolymph cortisol levels and tyrosinase activity across different tissues (hemolymph, muscle, hepatopancreas) among groups (RL > BL > GL > WL). Hepatopancreatic CAT activity in WL was significantly higher than that in GL and BL, whereas hepatopancreatic MDA content was highest in BL. Regarding chromatic parameters, the yellow color of the RL cephalothorax cuticle and the red color of the muscle were more pronounced than in WL, The chela cuticle of GL is darker than RL, while the red color of the chela cuticle was more pronounced than in WL.. For pigment content, cephalothorax cuticle astaxanthin content in BL was significantly higher than that in other light color groups, while abdominal cuticle astaxanthin content was lowest in BL. Chela cuticle astaxanthin content in RL was significantly higher than that in WL, and chela cuticle astaxanthin and lutein contents in WL were significantly lower than those in BL and GL. Compared with WL, hepatopancreatic glutathione S-transferase P1 (GSTP1) mRNA expression significantly decreased under colored light, whereas NinaB mRNA expression significantly increased under RL and BL. These results indicate that light color does not affect the morphological characteristics of P. clarkii but significantly modulates oxidative stress responses, physiological status and energy metabolism. Different light colors may mediate carotenoid transport and deposition by regulating the expression of GSTP1, NinaB, leading to specific chromatic differences in different body parts of P. clarkii. Comprehensive analysis revealed that the red light environment exerted a more positive effect on enhancing the body color of P. clarkii. This study provides a reference for revealing the mechanism of light color regulating crustacean physiological function and pigmentation and optimizing aquaculture model. Full article

Background: Irisin, a muscle-derived hormone, enhances the energy metabolism by activating the brown adipose tissue and acts as a bone-forming agent across the entire life span. No consistent clinical data in humans have been published so far to highlight if blood irisin as glucose/bone biomarker should be refined based on the vitamin D status (deficient or sufficient). Therefore, we aimed to objectively assess the level of irisin in female adults with abnormal and normal vitamin D status, as reflected by the level of 25-hydroxyvitamin (25OHD) in relationship with glucose and bone metabolic parameters. Methods: This pilot, prospective, exploratory study included eighty-nine menopausal women aged over 50. We excluded subjects with malignancies, bone and metabolic disorders, insulin treatment, and active endocrine disorders. Fasting profile included glycaemia, insulin, and glycated haemoglobin A1c (HbA1c). Then, 75 g oral glucose tolerance test (OGTT) included glycaemia and insulin assay after 60 and 120 min. Bone status involved bone turnover markers and central dual-energy X-ray absorptiometry providing bone mineral density (BMD) and trabecular bone score. Results: Eighty-nine subjects were included in the following two groups depending on 25OHD: vitamin D-deficient (VDD) group (N = 48; 25OHD < 30 ng/mL) and vitamin D-sufficient (VDS) group (N = 41; 25OHD ≥ 30 ng/mL). The two groups had similar age and menopausal period (62.29 ± 10.19 vs. 63.56 ± 8.16 years, respectively; 15.82 ± 9.55 vs. 16.11 ± 9.00 years, p > 0.5 for each). A statistically significant higher body mass index (BMI) was found in VDD vs. VDS group (32.25 ± 5.9 vs. 28.93 ± 4.97 kg/m², p = 0.006). Circulating irisin was similar between the groups as follows: median (IQR) of 91.85 (44.76–121.76) vs. 71.17 (38.76–97.43) ng/mL, p = 0.506. Fasting profile and OGTT assays showed no between-group difference. Median HOMA-IR in VDD group pointed out insulin resistance of 2.67 (1.31–3.29). Lowest mean/median T-scores at DXA for both groups were consistent with osteopenia category, but they were confirmed at different central sites as follows: femoral neck in both groups [VDD versus VDS group: −1.1 (−1.20–−0.90) vs. −1.1 (−1.49–−0.91), p = 0.526, respectively], only at lumbar spine for VDS group (T-score of −1.18 ± 1.13). The correlations between irisin and the mentioned parameters displayed a different profile when the analysis was performed in the groups with different 25OHD levels. In VDD group, irisin levels statistically significantly correlated with serum phosphorus (r = −0.32, p = 0.022), osteocalcin (r = −0.293, p = 0.038), P1NP (r = −0.297, p = 0.04), HbA1c (r = 0.342, p = 0.014), and BMI (r = 0.408, p = 0.003). Conclusions: This pilot study brings awareness in the analysis of irisin in relationship with glucose and bone-related biomarkers correlates, showing a distinct type of association depending on 25OHD level, which might represent an important crossroad in the multitude of irisin-activated signal transduction pathways. Full article

Abdominal fat deposition in chickens significantly impacts production efficiency and is influenced by complex genetic and molecular mechanisms. This review summarizes current genomic and transcriptomic research on the regulation of adipogenesis and fat accumulation in chickens, highlighting key genes and loci identified through genome-wide association studies as well as other candidates involved in lipogenesis, lipolysis, and transcriptional regulation. Major metabolic pathways, including MAPK, AMPK, PI3K/AKT/mTOR, TGFβ1/Smad3, FoxO, JAK–STAT, Wnt/β-catenin, and Sonic Hedgehog signaling, are examined for their roles in fat deposition. The regulatory functions of non-coding RNAs, including microRNAs, long non-coding RNAs, and circular RNAs, are discussed, focusing on their interactions with target mRNAs and signaling networks that control lipid metabolism, adipocyte differentiation, and energy balance. Integrating insights from both avian and human studies, this review emphasizes the molecular mechanisms underlying adipogenesis and highlights potential strategies for genetic selection aimed at reducing excessive abdominal fat and improving poultry productivity. Full article

This study explored the effects of Bifidobacterium animalis subspecies lactis CECT 8145 (B. animalis CECT 8145)—in both live probiotic and heat-treated postbiotic form—on metabolic health and digestion in male and female Labrador Retrievers during weight gain and loss. The study consisted of two, seven-week phases: weight gain (200% maintenance energy intake; Phase (1) and weight loss (100% maintenance energy requirement for ideal weight; Phase (2), separated by a 2-week washout period. In each phase, forty-five adult Labrador Retrievers (1.6–12.5 years) were randomly assigned to daily supplementation with live B. animalis CECT 8145 probiotic (PRO, n = 15), heat-treated B. animalis CECT 8145 postbiotic (POST, n = 15), or placebo control (CON, n = 15). Body weight, body condition score, fecal quality and food consumption were monitored throughout the study, and body composition, fecal, and blood samples were analyzed at the beginning and end of each phase. Digestibility was evaluated at the end of each phase. Post-prandial glucose responses were affected by intervention during weight loss, with a 6% reduction in the area under the curve (AUC) in POST compared to CON dogs (p = 0.035). Glucagon was decreased in females supplemented with POST (p = 0.0014), while POST males showed increased glucagon-like peptide-1 (GLP-1) compared to CON (p = 0.016) during weight gain. Serum GGT levels decreased, within the normal reference range, in POST compared to CON dogs during weight gain (post hoc p = 0.041). Fecal isovalerate was also reduced and fat digestibility increased (p = 0.026) in POST compared to CON (p = 0.018) during weight gain. There was a significant association between the group and gastric inhibitory polypeptide (GIP), with a decrease in GIP in POST over time (p = 0.030), and glucagon tended to be decreased in POST compared to CON (p = 0.073). Overall, these findings suggest supplementation with postbiotic B. animalis CECT 8145 may improve certain markers of Labrador retrievers’ metabolic health. Full article