PubMed

Food Res Int. 2024 Dec;198:115386. doi: 10.1016/j.foodres.2024.115386. Epub 2024 Nov 16.ABSTRACTThis study comprehensively investigated the impact of different storage times on the quality and metabolomic profiles of Liupao tea (LPT). The sensory evaluations revealed that both Maosheng (MS) and Tianyu (TY) teas exhibited a browning of tea appearance and brightening of tea infusion during storage. The taste evolved from bitterness and astringency to purity and briskness, while the aroma shifted from stuffy to woody and aged aromas. Notably, MS teas exhibited superior sensory quality after 10 years, while TY teas reached optimal quality in the 8th year of storage. Correlation analysis of metabolites and sensory attributes has underscored the integral influence of metabolites throughout the storage process, which significantly directed the development of tea quality. The non-volatile metabolites exerted significant influence on tea flavor by modulating key biochemical pathways, including the oxidation of catechins, the formation of alkaloids as well as the glycosylation and/or methylation of flavonoids. However, TY teas experienced both glycosylation and methylation, which promoted the transformation of bitterness and astringency, achieving a mellow and brisk taste more quickly than MS teas. The transformation pathways of volatile metabolites potentially involved the hydrolysis of linalool glycosides and phenylethanol glycosides, the synthesis of sesquiterpenes, the methylation of gallic acid and the degradation of carotenoids. However, the divergent trends observed in ketones and aldehydes between the two types of tea could culminate in distinct aromatic profiles, which might be due to different metabolic pathways or differences in the rates of metabolite formation and degradation during storage. Additionally, the antioxidant analysis revealed that both MS and TY teas exhibited a parabolic trend in comprehensive antioxidant capacity during storage, which primarily influenced by the oxidative polymerization of phenolic compounds and the glycosylation of flavonoids. In summary, this study emphasized the multifaceted attributes of tea quality and the importance of metabolites in shaping sensory quality and health properties. It was found that the optimal storage time of 8 to 10 years for LPT was conducive to attaining a desirable balance of flavor and health benefits.PMID:39643349 | DOI:10.1016/j.foodres.2024.115386

Food Res Int. 2024 Dec;198:115374. doi: 10.1016/j.foodres.2024.115374. Epub 2024 Nov 17.ABSTRACTTorreya grandis is a medicinally and nutritionally rich tree nut with high flavonoid content. However, a thorough evaluation of the variation in flavonoids among T. grandis cultivars remains to explore. In this study, we conducted a widely-targeted metabolomic analysis of five T. grandis cultivars, identifying 64 distinct flavonoids. Key subclasses of flavonoids, including flavan-3-ols, anthocyanidins, procyanidins, and flavonols, were characterized for their abundance and related to their potential health benefits. Our analysis revealed that T. grandis 'Shishengfei' exhibited the highest flavonoid diversity and content, while other cultivars showed relatively lower levels. By integrating transcriptome data, we identified genes and metabolic pathways associated with flavonoid biosynthesis, which could offer potential targets for metabolic engineering to enhance the flavonoid content in T. grandis. This research not only establishes a database of flavonoid components in T. grandis but also offers insights for selecting and breeding cultivars with enhanced health-promoting properties, contributing to the fields of food chemistry and nutrition.PMID:39643346 | DOI:10.1016/j.foodres.2024.115374

Food Res Int. 2024 Dec;198:115361. doi: 10.1016/j.foodres.2024.115361. Epub 2024 Nov 17.ABSTRACTMicrobial metabolism plays a critical role in the flavor development of Guangxi fermented bamboo shoots (GFBS). To clarify the role of microorganisms in flavor formation and predict the metabolic pathways of key characteristic flavor compounds, this study employed metabolomics, Odor Activity Value (OAV), and Taste Activity Value (TAV) calculations, integrated with Partial Least Squares Discriminant Analysis (PLS-DA), to investigate changes in GFBS flavors-represented by volatile flavor compounds, organic acids, and free amino acids-across a 30-day fermentation period. Metagenomic datasets were used to identify taxonomic and functional changes in the microbial community. As a result, 26 characteristic flavor compounds (OAV or TAV > 1) were identified in mature GFBS, and 23 differential flavor compounds were identified at different fermentation stages using PLS-DA (VIP > 1.2). The top 10 microbial genera associated with these characteristic flavor compounds were identified, including Acinetobacter, Enterobacter, Raoultella, Enterococcus, Klebsiella, Lactococcus, Leuconostoc, Weissella, Lactiplantibacillus and Limosilactobacillus. Based on these findings, a predictive metabolic network of key flavor compounds in GFBS was constructed, providing a comprehensive understanding of the diverse metabolic roles of microorganisms during fermentation. This work lays a theoretical foundation for the standardized production and quality control of GFBS flavor.PMID:39643345 | DOI:10.1016/j.foodres.2024.115361

Neuropharmacology. 2024 Dec 4:110246. doi: 10.1016/j.neuropharm.2024.110246. Online ahead of print.ABSTRACTParkinson's disease (PD) is a highly heterogeneous and therefore a possible cause of translation failure of drugs from animal testing to human treatments can be because existing models cannot replicate the entire spectrum of PD features. One of the theories of the origin of neurodegenerative diseases assumes metabolic dysfunction as a common fundamental thread of disease development. Intracerebroventricular administration of streptozotocin induces insulin resistance in the brain (Alzheimer's disease animal model). The aim of this project is to examine whether metabolic dysfunction caused by direct application of streptozotocin to brain region affected in PD (striatum) can induce characteristic PD symptoms. Adult male Wistar rats were given streptozotocin bilaterally or unilaterally in striatum. PET scan, cognitive, behavioural and motoric functions were tested one month after administration. Metabolite and protein analysis was done by untargeted metabolomics, ELISA and Western blot. Rats administered bilaterally showed motoric deficit, cognitive deficit of spatial learning and memory, fear conditioned and recognition memory, and anxiety-like behaviour, accompanied by impaired brain glucose uptake and metabolism. The results provide first evidence that bilateral intrastriatal administration of streptozotocin (particularly lower dose) can cause development of the hallmark PD symptoms. As metabolic dysfunction is increasingly associated with PD, an animal model with hypermetabolism in the early-on could be a better PD model for testing diverse therapeutics and the results could be better translated to humans. Further characterization is needed for understanding possible underlying mechanism and development of a new animal model for unique PD endophenotype expressing motoric, cognitive and metabolic symptomatology.PMID:39643239 | DOI:10.1016/j.neuropharm.2024.110246

Biochim Biophys Acta Mol Basis Dis. 2024 Dec 4:167613. doi: 10.1016/j.bbadis.2024.167613. Online ahead of print.ABSTRACTAcute pancreatitis (AP) is a severe inflammatory disorder associated with metabolic reprogramming and mitochondrial dysfunction. This study investigated central carbon metabolism alterations in pancreatic acinar cells during AP, elucidated the molecular mechanisms of tricarboxylic acid (TCA) cycle disorders, and explored the role of protein hypersuccinylation in AP pathogenesis. Using in vitro and in vivo AP models, targeted metabolomics and bioinformatics analyses revealed TCA cycle dysregulation characterized by elevated succinyl-CoA and decreased succinate levels. Colorimetric assays, mass spectrometry, and site-directed mutagenesis demonstrated that SIRT5 downregulation led to SUCLA2 hypersuccinylation at K118, inhibiting succinyl-CoA synthetase activity and triggering a vicious cycle of succinyl-CoA accumulation and SUCLA2 succinylation. Adenovirus-mediated SIRT5 overexpression and SUCLA2 knockdown clarified the SIRT5-SUCLA2 pathway's role in regulating TCA cycle disorders. Protein succinylation levels positively correlated with pancreatic tissue damage and mitochondrial injury severity. Succinylome analysis identified cytochrome c1 (CYC1) as a key hypersuccinylated protein, and the SIRT5-SUCLA2 pathway regulated its succinylation level and electron transport chain complex III activity. Hypersuccinylation induced mitochondrial DNA release, activating the cGAS-STING pathway, contributing to multiple organ dysfunction syndrome. Modulating the SIRT5-SUCLA2 axis attenuated TCA cycle dysregulation, protein hypersuccinylation, mitochondrial damage, and inflammatory responses in AP. These findings reveal novel mechanisms linking the SIRT5-SUCLA2 axis, TCA cycle dysfunction, and protein hypersuccinylation in AP pathogenesis, providing potential therapeutic targets for AP treatment.PMID:39643219 | DOI:10.1016/j.bbadis.2024.167613

J Affect Disord. 2024 Dec 4:S0165-0327(24)02008-1. doi: 10.1016/j.jad.2024.12.029. Online ahead of print.ABSTRACTBACKGROUND: Post-traumatic stress disorder (PTSD) is a debilitating chronic mental disorder that leads to reduced quality of life and increased economic burden. Observational studies have found an association between human blood metabolites and PTSD. Nonetheless, these studies have limitations and are subject to confounding factors as well as reverse causation. Herein, we employed a two-sample Mendelian randomization (MR) approach for the systematic analysis of the blood metabolites and PTSD causal link.METHODS: Data for the human blood metabolome, cerebrospinal fluid (CSF) metabolome, and PTSD were obtained from publicly available summary-level genome-wide association studies (GWAS), respectively. The inverse variance weighted (IVW) approach represented the main analytic method for assessing exposure-outcome causal associations, employing multiple sensitivity analyses to verify the results' stability. In addition, replication and meta-analysis, steiger test and reverse MR analysis methods were performed to clarify further that these metabolites have independent causal effects on PTSD. Finally, the results of blood and CSF metabolomics analyses were synthesized to obtain biological markers with a causal link to PTSD.RESULTS: Conclusively, we identified potential causal associations between six blood metabolites and PTSD. The sensitivity analyses elucidated the absence of pleiotropy or heterogeneity in the MR results. The Steiger test and reverse MR analysis did not reveal reverse causal associations, proving the robustness of our results. Combined blood and CSF metabolome analyses showed the same trend for theophylline.CONCLUSION: This study reveals a strong causal link between metabolites and PTSD, which can be used as a biomarker for clinical PTSD disease screening and prevention. This study also provides a new perspective on the mechanism of metabolite-mediated PTSD development by combining genomics and metabolomics.PMID:39643216 | DOI:10.1016/j.jad.2024.12.029

Int J Biol Macromol. 2024 Dec 4:138388. doi: 10.1016/j.ijbiomac.2024.138388. Online ahead of print.ABSTRACTTea leaf spot, caused by the fungus Didymella segeticola, occurs in the high-mountain tea plantations of Southwest China. Due to a limited understanding of the disease's epidemiology and the lack of comprehensive control measures, it has a significant negative impact on tea yield and quality. In this study, we revealed that D. segeticola infection begins when conidia germinate to form a germ tube on the leaf surface. The fungus then grows in the intercellular spaces of the leaf epidermal cells, invading tea tissue and causing necrotic lesions. This infection leads to significant alterations in the cell walls of spongy and palisade mesophyll cells, severely damaging chloroplasts. We employed transcriptomic and metabolomic analyses based on an in vitro infection model using matcha powder to uncover two key genes of D. segeticola: DsHAD (encoding holoacid dehydrogenase) and DsADH (encoding alcohol dehydrogenase). These genes are the first to be associated with conidiation, virulence, and sensitivity to oxidative stress. DsHAD regulates the virulence of D. segeticola by modulating glutamate homeostasis. Our results elucidate the infection strategy of D. segeticola on tea leaves and provide valuable data for future research on control measures for tea leaf spot.PMID:39643170 | DOI:10.1016/j.ijbiomac.2024.138388

J Mol Biol. 2024 Dec 4:168888. doi: 10.1016/j.jmb.2024.168888. Online ahead of print.ABSTRACTOsteoarthritis (OA) is the most common degenerative joint disease and the second leading cause of disability worldwide. Single-omics analyses are far from elucidating the complex mechanisms of lipid metabolic dysfunction in OA. This study identified a shared lipid metabolic signature of OA by integrating metabolomics, single-cell and bulk RNA-seq, as well as metagenomics. Compared to the normal counterparts, cartilagesin OA patients exhibited significant depletion of homeostatic chondrocytes (HomCs) (P=0.03) and showed lipid metabolic disorders in linoleic acid metabolism and glycerophospholipid metabolism which was consistent with our findings obtained from plasma metabolomics. Through high-dimensional weighted gene co-expression network analysis (hdWGCNA), weidentified PLA2G2A as a hub gene associated with lipid metabolic disorders in HomCs. And an OA-associated subtype of HomCs, namely HomC1 (marked by PLA2G2A, MT-CO1, MT-CO2, and MT-CO3) was identified, which also exhibited abnormal activation of lipid metabolic pathways. This suggests the involvement of HomC1 in OA progression through the shared lipid metabolism aberrancies, which were further validated via bulk RNA-Seq analysis. Metagenomic profiling identified specific gut microbial species significantly associated with the key lipid metabolism disorders, including Bacteroides uniformis (P<0.001, R=-0.52), Klebsiella pneumonia (P=0.003, R=0.42), Intestinibacter_bartlettii (P=0.009, R=0.38), and Streptococcus anginosus (P=0.009, R=0.38). By integrating the multi-omics features, a random forest diagnostic model with outstanding performance was developed (AUC=0.97). In summary, this study deciphered the crucial role of a integrated lipid metabolic signature in OA pathogenesis, and established a regulatory axis of gut microbiota-metabolites-cell-gene, providing new insights into the gut-joint axis and precision therapy for OA.PMID:39643156 | DOI:10.1016/j.jmb.2024.168888

Metab Eng. 2024 Dec 4:S1096-7176(24)00164-2. doi: 10.1016/j.ymben.2024.12.001. Online ahead of print.ABSTRACTLactate metabolism plays a critical role in mammalian cell bioprocessing, influencing cellular performance and productivity. The transition from lactate production to consumption, known as lactate metabolic shift, is highly beneficial and has been shown to extend culture lifespan and enhance productivity, yet its molecular drivers remain poorly understood. Here, we have explored the mechanisms that underpin this metabolic shift through two case studies, illustrating environmental- and genetic-driven factors. We characterised these study cases at process, metabolic and transcriptomic levels. Our findings indicate that glutamine depletion coincided with the timing of the lactate metabolic shift, significantly affecting cell growth, productivity and overall metabolism. Transcriptome analysis revealed dynamic regulation the ATF4 pathway, involved in the amino acid (starvation) response, where glutamine depletion activates ATF4 gene and its targets. Manipulating ATF4 expression through overexpression and knockdown experiments showed significant changes in metabolism of glutamine and lactate, impacting cellular performance. Overexpression of ATF4 increased cell growth and glutamine consumption, promoting a lactate metabolic shift. In contrast, ATF4 downregulation decreased cell proliferation and glutamine uptake, leading to production of lactate without any signs of lactate shift. These findings underscore a critical role for ATF4 in regulation of glutamine and lactate metabolism, related to phasic patterns of growth during CHO cell culture. This study offers unique insight into metabolic reprogramming during the lactate metabolic shift and the molecular drivers that determine cell status during culture.PMID:39643154 | DOI:10.1016/j.ymben.2024.12.001

Eur J Pharm Sci. 2024 Dec 4:106979. doi: 10.1016/j.ejps.2024.106979. Online ahead of print.ABSTRACTIn 2018 Amsterdam UMC decided to prepare chenodeoxycholic acid (CDCA) capsules (also known as pharmacy compounding) for patients with the genetic metabolic disease cerebrotendinous xanthomatosis (CTX) when the product with a marketing authorization was commercially unavailable for patients. However after reanalysis, unknown impurities were identified in the CDCA active pharmaceutical ingredient (API) using thin-layer chromatography from the European Pharmacopoeia (Ph.Eur.) monograph. Therefore the API did not comply with the Ph.Eur. specifications for related substances. As a result pharmacy compounding was halted and an investigation was initiated to identify and quantify the unknown impurities. Meanwhile, a second CDCA API was sourced from another manufacturer. However, this API also appeared to contain an unknown impurity. This impurity could be identified as a dimer of CDCA using reversed phase liquid chromatography mass spectrometry. Since the Ph.Eur. at the time did not describe a suitable analytical method for the quantification of this new impurity, a high pressure liquid chromatography with differential refractometer (HPLC-RI) method was developed to quantify the dimer. Subsequently, in 2019, a new draft version of the CDCA Ph.Eur. monograph was published, including the dimer as an additional impurity together with a HPLC-RI method for its identification and quantification. The CDCA-dimer is classified as non-toxic and permitted in the CDCA API up to a maximum of 0.5%. Because the API complied with the updated Ph.Eur. specifications, pharmacy compounding of CDCA capsules could be resumed.PMID:39643128 | DOI:10.1016/j.ejps.2024.106979

Bioresour Technol. 2024 Dec 4:131949. doi: 10.1016/j.biortech.2024.131949. Online ahead of print.ABSTRACTPolyhydroxyalkanoate (PHA) is considered a sustainable alternative to traditional petroleum-based plastics due to its biodegradability and biocompatibility. In this study, Acidovorax diaphorobacter ZCH-15, an efficient PHA-producing strain, was isolated from activated sludge. Using food waste-derived orange peel as a substrate, the strain initially achieved a PHA concentration of 0.39 g/L. Under optimal fermentation conditions (30℃, pH 8, 2 % inoculum concentration, and 30 g/L carbon source), the PHA concentration increased by 138 % to reach a maximum of 0.93 g/L. Proton nuclear magnetic resonance spectroscopy and gas chromatography analyses identified the PHA composition as poly(3-hydroxybutyrate-co-3-hydroxyvalerate), which exhibited high crystallinity and structural stability. Metabolomic analysis indicated that the tricarboxylic acid cycle and pentose phosphate pathway were involved in producing succinyl-CoA, a precursor required for PHA synthesis. This study demonstrates the potential for cost-effective industrial PHA production while enabling the high-value utilization of food waste.PMID:39643061 | DOI:10.1016/j.biortech.2024.131949

J Ethnopharmacol. 2024 Dec 4:119172. doi: 10.1016/j.jep.2024.119172. Online ahead of print.ABSTRACTETHNOPHARMACOLOGICAL RELEVANCE: Selaginella moellendorffii Hieron. has been used as ethnic drug for chronic inflammation treatment. Biflavonoids represent a crucial class of bioactive compounds recognized for their potent anti-inflammatory activity in S. moellendorffii (SM). However, the effective components, targets, and pathways that SM in anti-inflammasome remain unclear.AIM OF THE STUDY: Therefore, this study initially evaluated the effective components of SM and explored the underlying mechanisms.MATERIALS AND METHODS: Firstly, a series of biflavonoids were isolated from SM, and then all compounds were evaluated for their anti-inflammatory ability in the THP-macrophages co-stimulated with lipopolysaccharide (LPS) and NLRP3 inflammasome inducers. Secondly, transcriptomic analysis and metabolomics analysis revealed the differential genes and metabolites associated with effective components treatment. Finally, molecular docking of effective components with NLRP3 was performed and western blotting was performed in order to determine the expression of related proteins.RESULTS: Overall, eleven biflavonoids were successfully isolated from SM. Particularly, F7 exhibited the most potent inhibitory effect against NLRP3 inflammasome-mediated cytokines levels, cell membrane integrity and Ca2+ influx. Transcriptomic studies demonstrated that the differential genes (DEGs) were mainly enriched in NF-κB signaling pathway and NOD-like receptor signaling pathway. Metabolomics studies that the metabolites were mainly involved the pyrimidine metabolites. Further validation analysis manifested that F7's significant downregulation of NLRP3 inflammasome-related genes and proteins expression (P<0.05, P<0.01), encompassing both priming (NLRP3, TNF-α, p-p65/p65) and activation stages (IL-1β, IL-18, Caspase-1, GSDMD-N/GSDMD). Moreover, NLRP3 knockdown attenuated F7-mediated inhibition of pyroptosis. Finally, in silico results showed that F7 exhibited promising predicted binding affinity towards NLRP3.CONCLUSIONS: Collectively, these findings revealed an anti-inflammatory material basis for SM and confirmed F7 as a potent inhibitor of pyroptosis by suppressing NF-κB/NLRP3 Pathway.PMID:39643022 | DOI:10.1016/j.jep.2024.119172

Biomarkers. 2024 Dec 6:1-15. doi: 10.1080/1354750X.2024.2438734. Online ahead of print.ABSTRACTINTRODUCTION: Urine metabolomics offers a non-invasive approach to diagnose and manage inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), by identifying distinct metabolic signatures.OBJECTIVES: This narrative review summarizes current findings on urinary metabolites in IBD, evaluating their roles in disease differentiation, assessment of activity, and monitoring therapeutic response.METHODS: A comprehensive literature search of PubMed and MEDLINE up to October 2023 was conducted using keywords such as "urine metabolomics," "inflammatory bowel disease," "Crohn's disease," "ulcerative colitis," and "urinary biomarkers." Studies were included that described alterations to metabolic pathways, including those related to the urea cycle, central energy metabolism (Krebs cycle), amino acid metabolism, and neurotransmitters.RESULTS: Specific urinary metabolites differentiate IBD patients from healthy controls and between CD and UC. Decreased urinary levels of hippurate, acetate, methanol, formate, and methylamine are observed in IBD, indicating altered gut microbiota. In CD patients, urea cycle alterations include reduced urinary urea and ornithine with increased arginine. Changes in Krebs cycle intermediates show decreased citrate and succinate in adults, but increased fumarate and isocitrate in pediatric patients, reflecting energy metabolism differences. Amino acid metabolism differs by age: adults exhibit decreased urinary asparagine, lysine, and histidine, while pediatric patients show increased methionine, proline, aspartic acid, and isoleucine. Elevated urinary neurotransmitters like dopamine are noted in pediatric IBD patients. Urine metabolomics also can monitor treatment efficacy by distinguishing responders from non-responders to therapies and differentiating active disease from remission.CONCLUSION: Urine metabolomics provides promising, non-invasive biomarkers to enhance IBD diagnostics by distinguishing CD from UC and offering insights into underlying metabolic disturbances, paving the way for more precise, accessible patient care.PMID:39642943 | DOI:10.1080/1354750X.2024.2438734

Cell Metab. 2024 Dec 4:S1550-4131(24)00451-0. doi: 10.1016/j.cmet.2024.11.005. Online ahead of print.ABSTRACTHistone lysine lactylation is a physiologically and pathologically relevant epigenetic pathway that can be stimulated by the Warburg effect-associated L-lactate. Nevertheless, the mechanism by which cells use L-lactate to generate lactyl-coenzyme A (CoA) and how this process is regulated remains unknown. Here, we report the identification of guanosine triphosphate (GTP)-specific SCS (GTPSCS) as a lactyl-CoA synthetase in the nucleus. The mechanism was elucidated through the crystallographic structure of GTPSCS in complex with L-lactate, followed by mutagenesis experiments. GTPSCS translocates into the nucleus and interacts with p300 to elevate histone lactylation but not succinylation. This process depends on a nuclear localization signal in the GTPSCS G1 subunit and acetylation at G2 subunit residue K73, which mediates the interaction with p300. GTPSCS/p300 collaboration synergistically regulates histone H3K18la and GDF15 expression, promoting glioma proliferation and radioresistance. GTPSCS represents the inaugural enzyme to catalyze lactyl-CoA synthesis for epigenetic histone lactylation and regulate oncogenic gene expression in glioma.PMID:39642882 | DOI:10.1016/j.cmet.2024.11.005

Dev Cell. 2024 Nov 27:S1534-5807(24)00672-5. doi: 10.1016/j.devcel.2024.11.007. Online ahead of print.ABSTRACTThe gastric mucosa is a highly dynamic tissue that undergoes constant self-renewal through stem cell differentiation. Chief cells maintain a quiescent state in homeostasis but are responsible for regeneration after injury. Although the role of microbiome-host interactions in the intestine is well studied, less is known about these interactions in the stomach. Using the mouse organoid and germ-free mouse models, we show that microbiota-derived short-chain fatty acids (SCFAs) suppress the proliferation of chief cells in mice. This effect is mediated by activation of G-protein-coupled receptor 43. Most importantly, through metabolomics and transplantation studies, we show butyrate-producing Lactobacillus intestinalis modulates the proliferation of chief cells in mice. Our findings identify a mechanism by which the microbiota regulates the cell characteristics of chief cells, providing insight into the complex interplay between the host and its microbial environment and the mechanisms underlying gastric homeostasis, with potential therapeutic implications for gastric diseases.PMID:39642880 | DOI:10.1016/j.devcel.2024.11.007

Poult Sci. 2024 Dec 2;104(1):104619. doi: 10.1016/j.psj.2024.104619. Online ahead of print.ABSTRACTBirds' glycolipid metabolism has garnered considerable attention due to their fasting blood glucose levels being nearly twice those of mammals. While skeletal muscle is the primary insulin-sensitive tissue in mammals, the effects of insulin on chicken skeletal muscle remain unclear. In this study, the insulin-responsive metabolites were identified in broiler's pectoralis muscle (after 16 h of fasting) using widely targeted metabolomics. Glycolipid concentrations were measured using kits, and the expression of key genes involved in glucose metabolism was assessed via quantitative real-time PCR (qRT-PCR). The insulin tolerance test, performed by injecting 5 IU/kg body weight of insulin, demonstrated a rapid drop in blood glucose levels from 0 to 15 min, with a consistent reduction observed at 120 min (P < 0.01). Insulin did not alter glucose and glycogen content in chicken pectoralis; however, low-density lipoprotein (LDL, P < 0.05) levels were upregulated in the early phase (15 min). With an extended insulin duration (120 min), pectoralis glucose content increased (P < 0.05), accompanied by a reduction in TG levels (P < 0.05). Metabolomic analysis revealed that insulin promotes the downregulation of 63 out of 71 metabolites at 15 min and the upregulation of 101 out of 134 metabolites at 120 min, mainly associated with lysine degradation and thyroid hormone signaling pathways, respectively. 7 metabolites were dynamically modulated in the same manner over time (2 up-up and 5 down-down). Early insulin inhibited glycolysis, evidenced by the reduction in phosphoenolpyruvate levels and hexokinase 2 (HK2) expression; however, insulin promoted glucose uptake through the activation of glucose transporter 4 (GLUT4) and enhanced glycolysis, accompanied by elevated fatty acid metabolism at the later phase. In conclusion, insulin dynamically regulates the metabolomics of the pectoralis muscle over time. Initially, chicken muscle tissues downregulate metabolic activities to accommodate the new signaling state, followed by significant upregulation to meet heightened metabolic demands. Extended insulin monitoring promotes glucose uptake and glycolysis, alongside enhanced fatty acid metabolism. This research provides insights into the potential mechanisms of insulin action in chicken muscles.PMID:39642750 | DOI:10.1016/j.psj.2024.104619

J Hazard Mater. 2024 Nov 30;484:136691. doi: 10.1016/j.jhazmat.2024.136691. Online ahead of print.ABSTRACTThe study explored the ecotoxicological effects of chronic exposure to microplastic (MP) on adult zebrafish, focusing on environmentally relevant concentrations of polyethylene (PE) beads and polyester (PES). High-throughput untargeted metabolomics via UPLC-QToF-MS and 16S metagenomics for gut microbiota analysis were used to assess ecotoxicity in zebrafish exposed to varying concentrations of PE and PES. The VIP (Variable Importance in Projection) scores indicated PE exposure primarily impacted phospholipids, ceramides, and nucleotide-related compounds, while PES exposure led to alterations in lipid-related compounds, chitin, and amino acid derivatives. From MSEA (Metabolite Set Enrichment Analysis) and Mummichog analyses, PE and PES significantly disrupted key metabolomic pathways associated with inflammation, immune responses, and apoptosis, including leukotriene and arachidonic acid metabolism and the formation of putative anti-inflammatory metabolites from EPA. PE caused physical disruption and inflammation of the epithelial barrier, whereas PES affected gut microbiota interactions, impairing digestion and metabolism. Although alpha diversity within the gut microbiome remained stable, beta diversity analysis revealed significant shifts in microbial composition and structure, suggesting a disruption of functional balance and an increased susceptibility to pathogens. Chronic PE and PES exposures induced shifts in the gut microbial community and interaction network with potential increases in pathogenic bacteria and alteration in commensal bacteria, demonstrating the microbiome's resilience and adaptability to stressors of MPs exposure. High-throughput metabolomics and 16S metagenomics revealed potential chronic diseases associated with inflammation, immune system disorders, metabolic dysfunction, and gut dysbiosis, highlighting the complex relationship between gut microbiome resilience and metabolic disruption under MP-induced stress, with significant ecological implications.PMID:39642737 | DOI:10.1016/j.jhazmat.2024.136691

J Hazard Mater. 2024 Nov 28;484:136712. doi: 10.1016/j.jhazmat.2024.136712. Online ahead of print.ABSTRACTDeveloping methodologies for performing multi-omics with one sample has been challenging in zebrafish toxicology; however, related studies are lacking. A new strategy for the simultaneous analysis of metabolomics and lipidomics in zebrafish embryos was proposed and applied to explore the neurotoxicity mechanisms of perfluorooctanesulfonate (PFOS). Metabolite and lipid profiled simultaneously with methyl tert-butyl ether (MTBE) were compared with individual results from other extraction solvents. Behavioral alterations were measured after the zebrafish embryos were exposed to 0.1-20 μM PFOS for 5 days. The metabolite-lipid profiles of the MTBE-based strategy analyzed with optimized larval pooling size of 30 were comparable to those of other extraction solvents, indicating the feasibility and efficiency of MTBE-based multi-omics analysis. Many metabolites and lipids, which were enriched more than those previously reported, completed the toxicity pathways involved in energy metabolism and sphingolipids, improving our understanding of PFOS-induced neurotoxicity mechanism manifested by increased movement under dark conditions. Our novel MTBE-based strategy enabled the multi-omics analysis of one sample with minimal use of zebrafish embryos, thereby improving data reliability on changes in multi-layered biomolecules. This study will advance multi-omics technologies that are critical to elucidating the toxicity mechanisms of toxic chemicals including per- and polyfluoroalkyl substances.PMID:39642725 | DOI:10.1016/j.jhazmat.2024.136712

J Breath Res. 2024 Dec 6. doi: 10.1088/1752-7163/ad9b46. Online ahead of print.ABSTRACTVolatolomics (or volatilomics), the study of volatile organic compounds, has emerged as a crucial field of metabolomics due&#xD;to its potential for non-invasive diagnostics and disease monitoring. However, analyzing high-resolution data generated by&#xD;mass spectrometry-based instrumentation remains challenging. This comprehensive guide provides an in-depth exploration&#xD;of volatolomics data analysis, highlighting the importance of subsequent steps, including data cleaning, pretreatment, and&#xD;statistical and machine learning techniques (dimensionality reduction, clustering, classification, and variable selection). The&#xD;choice of these methods, and the integration of data handling practices, such as missing data imputation, outlier detection,&#xD;model validation, and data integration, significantly impact the identification of meaningful metabolites and the accuracy of&#xD;diagnostic conclusions. This guide aims to familiarize the reader with the implications of various data analysis techniques in&#xD;volatolomics and their suitability for different applications. It emphasizes the necessity of understanding the strengths and&#xD;limitations of each method to make informed decisions that enhance the reliability of findings. By outlining these methodologies,&#xD;the guide aims to equip researchers with the knowledge needed to navigate the complexities of volatolomics data analysis. The&#xD;careful consideration of experimental design, data collection, and processing strategies is essential for the identification of&#xD;biomarkers, ultimately advancing the field and improving the understanding of metabolic processes in health and disease.PMID:39642393 | DOI:10.1088/1752-7163/ad9b46

Sci Immunol. 2024 Dec 6;9(102):eadl1467. doi: 10.1126/sciimmunol.adl1467. Epub 2024 Dec 6.ABSTRACTThe molecular mechanisms by which worm parasites evade host immunity are incompletely understood. In a mouse model of intestinal helminth infection using Heligmosomoides polygyrus bakeri (Hpb), we show that helminthic glutamate dehydrogenase (heGDH) drives parasite chronicity by suppressing macrophage-mediated host defense. Combining RNA-seq, ChIP-seq, and targeted lipidomics, we identify prostaglandin E2 (PGE2) as a major immune regulatory mechanism of heGDH. The induction of PGE2 and other immunoregulatory factors, including IL-12 family cytokines and indoleamine 2,3-dioxygenase 1, by heGDH required p300-mediated histone acetylation, whereas the enzyme's catalytic activity suppressed the synthesis of type 2-promoting leukotrienes by macrophages via 2-hydroxyglutarate. By contrast, the induction of immunoregulatory factors involved the heGDH N terminus by potentially mediating interactions with cellular targets (CD64 and GPNMB) identified by proteomics. Type 2 cytokines counteracted suppressive effects of heGDH on host defense, indicating that type 2 immunity can limit helminth-driven immune evasion. Thus, helminths harness a ubiquitous metabolic enzyme to epigenetically target type 2 macrophage activation and establish chronicity.PMID:39642243 | DOI:10.1126/sciimmunol.adl1467