Search Results (708)

Siniperca chuatsi is an important high-quality freshwater aquaculture species in China. In nature, it feeds exclusively on live food. In this study, domesticated juvenile S. chuatsi were divided into three groups and fed live food (group L), compound feed (group C), or a mixed diet (group M) for three months to investigate the molecular mechanisms underlying adaptation to compound feed. Histopathological examination revealed that compound feed consumption induced looser liver cell arrangement, hepatocyte morphological irregularities, and vacuolization. A total of 1033 and 1428 differentially expressed genes (DEGs), and 187 and 184 differential metabolites (DMs), were identified in the C vs. L and C vs. M groups, respectively. Transcriptomic analysis revealed that the significantly and commonly enriched metabolic pathways shared by both comparison groups were predominantly involved in amino acid, carbohydrate, and lipid metabolisms. Metabolomic analysis demonstrated that the significantly and commonly enriched metabolic pathways shared by both comparison groups were the arachidonic acid metabolism, linoleic acid metabolism, oxidative phosphorylation, and PPAR signalling pathways. Integrated omics analysis showed that the PPAR signalling pathway was the only significantly co-enriched pathway across both omics datasets. This study provides new insights into the molecular mechanisms of compound feed adaptation and provides theoretical support for selecting feed traits in S. chuatsi. Full article

(1) Background: Epidemiological studies link ozone (O₃) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O₃ were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O₃ exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O₃-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O₃ triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets. Full article

Background/Objective: The hepatitis B virus (HBV) can cause chronic hepatitis B (CHB), which can rapidly progress into fatal liver cirrhosis (CHB-LC) and hepatocellular carcinoma (CHB-HCC). Methods: In this study, we investigated metabolites associated with distinct clinical stages of HBV infection for the identification of stage-specific serum metabolite biomarkers using ¹H-NMR-based metabolomics. Results: A total of 64 serum metabolites were identified, among which six core discriminatory metabolites, namely isoleucine, tryptophan, histamine (for CHB), and pyruvate, TMAO, lactate (for CHB-HCC), were consistently significant across univariate and multivariate statistical analyses, including ANOVA with FDR, OPLS-DA, and VIP scoring. These metabolites were closely linked to key metabolic pathways, such as propanoate metabolism, pyruvate metabolism, and the Warburg effect. Conclusions: The findings suggest that these six core metabolites serve as potential stage-specific biomarkers for CHB, CHB-LC, and CHB-HCC, respectively, and offer a foundation for the future development of metabolomics-based diagnostic and therapeutic strategies. Full article

The global obesity epidemic and associated metabolic disorders present urgent public health challenges. This study employed a multi-omics approach (lipidomics, metabolomics, and gut microbiome analysis) to investigate how Bletilla striata polysaccharides (BSPs) and composite polysaccharides modulate liver lipid metabolism and gut microbiota in high-fat diet (HFD)-induced obese mice. HFD elevated hepatic phosphatidylcholines, cholesteryl esters (CEs), and acylcarnitines (CARs), alongside increased cecal choline and trimethylamine. BSP interventions reduced hepatic CEs, free fatty acids (FAs), CARs, and cecal sarcosine while restoring gut microbial diversity. Notably, BSP enriched beneficial genera, including Jeotgalicoccus and Atopostipes, and the network analysis revealed negative correlations between these genera and hepatic triglycerides (TGs), implicating the gut–liver axis in lipid metabolism regulation. These findings elucidate the anti-obesity mechanisms of polysaccharides through gut microbiota remodeling and cross-tissue metabolic interactions, providing a foundation for leveraging plant polysaccharides in developing safer, effective obesity therapies. Full article

Background: Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive disease that easily develops into cirrhosis and hepatocellular carcinoma, but its pathogenesis is not clear, and most therapeutic drugs have obvious limitations. However, Babao Dan (BBD) has a good therapeutic effect on liver disease, but its treatment mechanism is still to be studied. Therefore, we further investigated the mechanism of BBD in treating MASH. Methods: We predicted BBD-related targets through network pharmacology and further verified the binding ability of BBD-related targets through molecular docking. We also detected relevant indicators before and after model treatment, as well as metabolomics analysis and identification of the mechanism of action of BBD on MASH. Results: Through network pharmacology methods, 158 key cross targets and the top 10 core targets were identified, and it was determined that the PI3K-AKT signaling pathway plays an important regulatory role in the treatment of MASH with BBD. The molecular docking results indicate that the representative compounds quercetin and 17 Beta Estradiol have good binding activity with five core targets. Metabolomics has identified four metabolic biomarkers, such as Piceid, and it is determined that the key pathway for BBD treatment of MASH is the bile secretion pathway. Conclusions: BBD effectively treats MASH by modulating Piceid and other biomarkers, targeting ESR1 and other core proteins via quercetin and 17-beta-estradiol, and regulating the PI3K-AKT and bile secretion pathways to alleviate liver injury. Full article

Marek’s disease (MD), induced by the highly contagious Marek’s disease virus (MDV), remains a significant challenge to global poultry health despite extensive vaccination efforts. This study employed integrated transcriptomic and metabolomic analyses to investigate liver responses in naturally MDV-infected Wenchang chickens during late infection stages. RNA sequencing identified 959 differentially expressed genes (DEGs) between the infected and uninfected groups. Functional enrichment analysis demonstrated that these DEGs were primarily associated with canonical pathways related to metabolism and cellular processes, including lipid, carbohydrate, and amino acid metabolism, as well as the p53 signaling pathway, cell cycle, and apoptosis. Ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) detected 561 differentially expressed metabolites (DEMs), showing near-significant enrichment (p = 0.069) in phenylalanine metabolism. Integrated analysis of transcriptomics and metabolomics data highlighted that critical gene–metabolite pairs such as SGPL1-palmitaldehyde–sphinganine-1-phosphate and ME1-NADP+–malic acid potentially mediate functional crosstalk between sphingolipid metabolism and cellular redox homeostasis during viral oncogenesis. This comprehensive mapping of regulatory networks provides insights into host–virus interactions during MDV pathogenesis, offering potential applications in immunomodulation approaches, targeted therapeutic strategies, and vaccine adjuvant development. Full article

Oxidative stress (OS) is a major concern in young poultry and livestock, prompting extensive research on OS models. This study aimed to systematically investigate the dynamic effects and temporal trends of OS induced with lipopolysaccharide (LPS) over time. Twenty-eight piglets were randomly divided into four groups and equally intraperitoneally injected with LPS at doses of 0 μg/kg (control), 50 μg/kg (L-LPS), 100 μg/kg (M-LPS) and 150 μg/kg (H-LPS) body weight, respectively. The results showed that total antioxidant capacity (T-AOC), total superoxide dismutase (T-SOD), and catalase (CAT) were decreased, while malondialdehyde (MDA), nitric oxide (NO), inducible nitric oxide synthase (iNOS), interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNF-α), diamine oxidase (DAO) and D-lactic acid (D-LA) were increased in the M-LPS and H-LPS group on day 1 in comparison with the control group, but no differences were found among treatments on day 7. However, LPS treatments gave rise to varying degrees of pathological injury in the intestines, livers and spleens on day 7. Metabolomics analysis indicated that compared with the control group, glycyl-valine, histamine and lepidine F were decreased in the M-LPS group. Most differentially expressed metabolites were enriched in amino acid-related metabolism pathways on both day 1 and day 7. Microbiome analysis identified that Oscillibacter_sp._CAG:241 was decreased in the M-LPS group compared with the control group on day 1, while Bacteroides_thetaiotaomicron and Lactobacillus_amylovorus were reduced in the M-LPS group on day 7. Collectively, an LPS dose of 100 μg/kg body weight is optimal for inducing acute inflammation in Wuzhishan miniature pigs. These findings highlight the importance of considering both the duration of OS induction and the specific research objectives when establishing OS models. Full article

Cholesterol stress profoundly modulates cellular processes, but its underlying mechanisms remain incompletely understood. To investigate cholesterol-responsive networks, we performed integrated transcriptome (RNA-seq) and metabolome (LC-MS) analyses on HeLa cells treated with cholesterol for 6 and 24 h. Through transcriptomic analysis of cholesterol-stressed HeLa cells, we identified stage-specific responses characterized by early-phase stress responses and late-phase immune-metabolic coordination. This revealed 1340 upregulated and 976 downregulated genes after a 6 h cholesterol treatment, including induction and suppression of genes involved in cholesterol efflux and sterol biosynthesis, respectively, transitioning to Nuclear Factor kappa-B (NF-κB) activation and Peroxisome Proliferator-Activated Receptor (PPAR) pathway modulation by 24 h. Co-expression network analysis prioritized functional modules intersecting with differentially expressed genes. We also performed untargeted metabolomics using cells treated with cholesterol for 6 h, which demonstrated extensive remodeling of lipid species. Interestingly, integrated transcriptomic and metabolic analysis uncovered GFPT1-driven Uridine Diphosphate-N-Acetylglucosamine (UDP-GlcNAc) accumulation and increased taurine levels. Validation experiments confirmed GFPT1 upregulation and ANGPTL4 downregulation through RT-qPCR and increased O-GlcNAcylation via Western blot. Importantly, clinical datasets further supported the correlations between GFPT1/ANGPTL4 expression and cholesterol levels in Non-Alcoholic Steatohepatitis (NASH) liver cancer patients. This work establishes a chronological paradigm of cholesterol sensing and identifies GFPT1 and ANGPTL4 as key regulators bridging glycosylation and lipid pathways, providing mechanistic insights into cholesterol-associated metabolic disorders. Full article

Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent condition worldwide and represents a major global health challenge. Pharmacological and pharmacodynamic results indicate that aspirin eugenol ester (AEE) performs various pharmacological activities. However, it is unclear whether AEE can ameliorate the NAFLD. This study investigated the ameliorative effects of AEE on glucose and lipid metabolism disorders by in vitro and in vivo experiments. In the cellular model, TC increased to 0.104 μmol/mg and TG increased to 0.152 μmol/mg in the model group, while TC decreased to 0.043 μmol/mg and TG decreased to 0.058 μmol/mg in the AEE group. In the model group, the area occupied by lipid droplets within the visual field was significantly elevated to 17.338%. However, the administration of AEE resulted in a substantial reduction in this area to 10.064%. AEE significantly reduced the lipid droplet area and TC and TG levels (p < 0.05), increased bile acids in the cells and in the medium supernatant (p < 0.05), and significantly up-regulated the expression of LRH-1, PPARα, CYP7A1, and BSEP mRNA levels (p < 0.05) compared to the model group. In the animal model, different doses of AEE administration significantly down-regulated the levels of TC, TG, LDL, GSP, and FBG (p < 0.05) compared to the high-fat-diet (HFD) group, and 216 mg/kg of AEE significantly improved hepatocellular steatosis, attenuated liver injury, and reduced the area of glycogen staining (p < 0.05). In the HFD group, the glycogen area within the visual field exhibited a significant increase to 18.250%. However, the administration of AEE resulted in a notable reduction in the glycogen area to 13.314%. Liver and serum metabolomics results show that AEE can reverse the metabolite changes caused by a HFD. The major metabolites were involved in seven pathways, including riboflavin metabolism, glycerophospholipid metabolism, tryptophan metabolism, primary bile acid biosynthesis, biosynthesis of unsaturated fatty acids, nicotinate and nicotinamide metabolism, and tryptophan metabolism. In conclusion, AEE had a positive regulatory effect on NAFLD. Full article

Background: Fish escape events from aquaculture facilities are increasing and pose significant ecological, economic, and traceability concerns. Accurate methods to differentiate between wild, cultured, and escaped fish are essential for fishery management and seafood authentication. Methods: This study analyzed muscle tissue from Sparus aurata, Dicentrarchus labrax, and Argyrosomus regius using a multiomics approach. Heavy metals were quantified by ICP-MS, fatty acid profiles were assessed via GC-MS, and metabolomic and lipidomic signatures were identified using 1H NMR spectroscopy. Multivariate statistical models (MDS and PLS-LDA) were applied to classify fish origins. Results: Wild seabream showed significantly higher levels of arsenic (9.5-fold), selenium (3.5-fold), and DHA and ARA fatty acids (3.2-fold), while cultured fish exhibited increased linoleic and linolenic acids (6.5-fold). TMAO concentrations were up to 5.3-fold higher in wild fish, serving as a robust metabolic biomarker. Escaped fish displayed intermediate biochemical profiles. Multivariate models achieved a 100% classification accuracy across species and analytical techniques. Conclusions: The integration of heavy metal analysis, fatty acid profiling, and NMR-based metabolomics enables the accurate differentiation of fish origin. While muscle tissue provides reliable biomarkers relevant to human exposure, future studies should explore additional tissues such as liver and gills to improve the resolution of traceability. These methods support seafood authentication, enhance aquaculture traceability, and aid in managing the ecological impacts of escape events. Full article

Streptococcus agalactiae (SA) is a severe prevalent pathogen, resulting in high morbidity and mortality in the global tilapia industry. With increasing bacterial resistance to antibiotics, alternative strategies are urgently needed. This study aims to investigate the antibacterial activity and the underlying mechanisms of the natural product xanthohumol (XN) against SA infection in tilapia (Oreochromis niloticus). The results showed that XN could significantly reduce the bacterial loads of SA in different tissues (liver, spleen and brain) after treatment with different tested concentrations of XN (12.5, 25.0 and 50.0 mg/kg). Moreover, XN could improve the survival rate of SA-infected tilapia. 16S rRNA gene sequencing demonstrated that the alpha-diversity index (Chao1 and Shannon_e) was significantly increased in the XN-treated group (MX group) compared to the SA-infected group (CG group) (p < 0.05), and the Simpson diversity index significantly decreased. The Bray–Curtis similarity analysis of non-metric multidimensional scaling (NMDS) and principal coordinate analysis (PCA) showed that there were significant differences in microbial composition among groups. At the phylum level, the relative abundance of the phyla Actinobacteria, Proteobacteria and Bacteroidetes decreased in the MX group compared to the CG group, while the relative abundance of the phyla Fusobacteria, Firmicutes and Verrucomicrobia increased. Differences were also observed at the genus level; the relative abundance of Mycobacterium decreased in the MX group, but the abundance of Cetobacterium and Clostridium_sensu_stricto_1 increased. Metabolomics analysis revealed that XN changed the metabolic profile of the liver and significantly enriched aspartate metabolism, glycine and serine metabolism, phosphatidylcholine biosynthesis, arginine and proline metabolism, glutamate metabolism, urea cycle, purine metabolism, methionine metabolism, betaine metabolism, and carnitine synthesis. Correlation analysis indicated an association between the intestinal microbiota and metabolites. In conclusion, XN may be a potential drug for the prevention and treatment of SA infection in tilapia, and its mechanism of action may be related to the regulation of the intestinal microbiota and liver metabolism. Full article

Background/Objectives: Obesity is increasingly recognized as a global health concern due to its association with metabolic disorders and gut microbiota dysbiosis. While probiotics offer promise in regulating gut microbiota and improving host metabolism, strain-specific effects remain underexplored, particularly for canine-derived probiotics. This study aimed to isolate and characterize a novel probiotic strain, Ligilactobacillus animalis LA-1, and evaluate its anti-obesity effects and underlying mechanisms using a high-fat diet (HFD)-induced obese mouse model. Methods: LA-1 was isolated from the feces of a healthy dog and assessed for probiotic potential in vitro, including gastrointestinal tolerance, bile salt hydrolase activity, cholesterol-lowering capacity, and fatty acid absorption. Male C57BL/6J mice were fed either a standard chow diet or an HFD for 16 weeks, with HFD mice receiving oral LA-1 supplementation (2 × 10⁹ CFU/day). Multi-omics analyses, including 16S rRNA gene sequencing, short-chain fatty acid (SCFA) quantification, and untargeted liver metabolomics, were employed to investigate the effects of LA-1 on gut microbiota composition, metabolic pathways, and obesity-related phenotypes. Results: LA-1 supplementation significantly alleviated HFD-induced weight gain, hepatic lipid accumulation, and adipose tissue hypertrophy, without affecting food intake. It improved serum lipid profiles, reduced liver injury markers, and partially restored gut microbiota composition, decreasing the Firmicutes/Bacteroidetes ratio and enriching SCFA-producing genera. Total SCFA levels, particularly acetate, propionate, and butyrate, increased following LA-1 treatment. Liver metabolomics revealed that LA-1 modulated pathways involved in lipid and amino acid metabolism, resulting in decreased levels of acetyl-CoA, triglycerides, and bile acids. Conclusions: L. animalis LA-1 exerts anti-obesity effects via gut microbiota modulation, enhanced SCFA production, and hepatic metabolic reprogramming. These findings highlight its potential as a targeted probiotic intervention for obesity and metabolic disorders. Full article

Background: Huang Qin Decoction (HQD) is a well-established Traditional Chinese Medicine (TCM) formulation recognized for its application in the treatment of colorectal cancer (CRC). However, the precise therapeutic mechanisms remain inadequately defined. Methods: This study integrates metabolomics from a mouse model and network pharmacology to screen potential targets and bio-active ingredients of HQD. The pharmacological activity of HQD for CRC was evidenced via single-cell RNA sequencing (scRNA-seq), molecular docking, and molecular dynamics simulations. Atomic force microscopy (AFM) assays and cellular experimental validation were used to confirm the relative mechanisms. Results: The metabolite profile undergoes significant alterations, with metabolic reprogramming evident during the malignant progression of CRC liver metastasis. Network pharmacology analysis identified that HQD regulates several metabolic pathways, including arginine biosynthesis, alanine, aspartate, and glutamate metabolism, nitrogen metabolism, phenylalanine metabolism, and linoleic acid metabolism, by targeting key proteins such as aspartate aminotransferase (GOT1), cytochrome P450 1A2 (CYP1A2), and carbonic anhydrase 2 (CA2). ScRNA-seq analysis indicated that HQD may enhance the functionality of cytotoxic T cells, thereby reversing the immunosuppressive microenvironment. Virtual verification revealed a strong binding affinity between the identified hub targets and active constituents of HQD, a finding subsequently corroborated by AFM assays. Cellular experiments confirmed that naringenin treatment inhibits the proliferation, migration, and invasion of CRC cells by downregulating GOT1 expression and disrupting glutamine metabolism. Conclusions: Computational prediction and in vitro validation reveal the active ingredients, potential targets, and molecular mechanisms of HQD against CRC liver metastasis, thereby providing a scientific foundation for the application of TCM in CRC treatment. Full article

The need to maximize aquaculture production while addressing environmental and food security challenges posed by climate change has driven research towards the development of functional aquafeeds that enhance performance and immunity in farmed species. However, exposure to dietary and environmental stressors affects marine organisms, altering key metabolic pathways best understood through high-throughput “omics” tools. This study assessed the effects of Asparagopsis taxiformis supplementation on central metabolic pathways by analyzing changes in primary metabolite levels in the liver of farmed Diplodus sargus under optimal and suboptimal temperature conditions. Results showed that seaweed supplementation had a beneficial effect on the fish’s primary metabolome; however, inclusion levels and rearing conditions played a crucial role in determining outcomes. While 1.5% supplementation maintained a balanced primary metabolome under optimal temperature conditions, 3.0% supplementation most effectively mitigated the adverse effects of acute thermal stress during a marine heatwave. These findings highlight the nutritive and functional potential of A. taxiformis supplementation in aquafeeds for marine omnivorous fish species and emphasize the importance of evaluating functional aquafeeds under suboptimal rearing conditions. Overall, our results demonstrate the value of metabolomics in elucidating the molecular basis underlying biological pathways in farmed marine fish and optimizing production through climate-smart dietary strategies. Full article

As consumer demand for quality fish products continues to rise, quality has become a key factor in market competition. Ecological aquaculture research is exploring various farming methods to balance high-quality demand with environmental protection. This study compared three aquaculture models—cage culture (CG), recirculating aquaculture (RAG), and rice–fish co-culture (RG)—by analyzing muscle quality (AOAC, GC-MS), intestinal microbiota (16S rRNA), and liver metabolism (LC-MS) to assess their effects on M. albus. In terms of muscle quality, the RG group showed increased levels of EPA and DHA, reduced muscle moisture and crude lipid content, and enhanced crude protein accumulation. The crude protein content was significantly higher in the RAG group than in the CG group (p < 0.05). The RG group also had the highest levels of total, essential, and umami amino acids, followed by the RAG and CG groups. In terms of intestinal microbiota, the RG group had the highest microbial diversity and stability, with increased abundance of Firmicutes and Bacteroidetes and decreased levels of Proteobacteria. Compared to the CG, the RAG group also showed increased microbial diversity and a reduction in pathogenic genera. Liver metabolomics analysis demonstrated that the RG group had significant advantages over the CG group in amino acid, lipid, and energy metabolism. The RAG group exhibited upregulation of glycerophospholipid metabolism and a decrease in oxidative stress marker levels. Overall, the RG group enhanced muscle quality and optimized intestinal and liver metabolism in M. albus. Full article