PubMed

Related Articles Investigation of α-Glucosidase Inhibitory Metabolites from Tetracera scandens Leaves by GC-MS Metabolite Profiling and Docking Studies. Biomolecules. 2020 Feb 12;10(2): Authors: Nokhala A, Siddiqui MJ, Ahmed QU, Ahamad Bustamam MS, Zakaria AZA Abstract Stone leaf (Tetracera scandens) is a Southeast Asian medicinal plant that has been traditionally used for the management of diabetes mellitus. The underlying mechanisms of the antidiabetic activity have not been fully explored yet. Hence, this study aimed to evaluate the α-glucosidase inhibitory potential of the hydromethanolic extracts of T. scandens leaves and to characterize the metabolites responsible for such activity through gas chromatography-mass spectrometry (GC-MS) metabolomics. Crude hydromethanolic extracts of different strengths were prepared and in vitro assayed for α-glucosidase inhibition. GC-MS analysis was further carried out and the mass spectral data were correlated to the corresponding α-glucosidase inhibitory IC50 values via an orthogonal partial least squares (OPLS) model. The 100%, 80%, 60% and 40% methanol extracts displayed potent α-glucosidase inhibitory potentials. Moreover, the established model identified 16 metabolites to be responsible for the α-glucosidase inhibitory activity of T. scandens. The putative α-glucosidase inhibitory metabolites showed moderate to high affinities (binding energies of -5.9 to -9.8 kcal/mol) upon docking into the active site of Saccharomyces cerevisiae isomaltase. To sum up, an OPLS model was developed as a rapid method to characterize the α-glucosidase inhibitory metabolites existing in the hydromethanolic extracts of T. scandens leaves based on GC-MS metabolite profiling. PMID: 32059529 [PubMed - in process]

42 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

42 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/15PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Urinary chemical fingerprint left behind by repeated NSAID administration: Discovery of putative biomarkers using artificial intelligence. PLoS One. 2020;15(2):e0228989 Authors: Broughton-Neiswanger LE, Rivera-Velez SM, Suarez MA, Slovak JE, Piñeyro PE, Hwang JK, Villarino NF Abstract Prediction and early detection of kidney damage induced by nonsteroidal anti-inflammatories (NSAIDs) would provide the best chances of maximizing the anti-inflammatory effects while minimizing the risk of kidney damage. Unfortunately, biomarkers for detecting NSAID-induced kidney damage in cats remain to be discovered. To identify potential urinary biomarkers for monitoring NSAID-based treatments, we applied an untargeted metabolomics approach to urine collected from cats treated repeatedly with meloxicam or saline for up to 17 days. Applying multivariate analysis, this study identified a panel of seven metabolites that discriminate meloxicam treated from saline treated cats. Combining artificial intelligence machine learning algorithms and an independent testing urinary metabolome data set from cats with meloxicam-induced kidney damage, a panel of metabolites was identified and validated. The panel of metabolites including tryptophan, tyrosine, taurine, threonic acid, pseudouridine, xylitol and lyxitol, successfully distinguish meloxicam-treated and saline-treated cats with up to 75-100% sensitivity and specificity. This panel of urinary metabolites may prove a useful and non-invasive diagnostic tool for monitoring potential NSAID induced kidney injury in feline patients and may act as the framework for identifying urine biomarkers of NSAID induced injury in other species. PMID: 32053695 [PubMed - in process]

Related Articles 2'-O-ribose methylation of transfer RNA promotes recovery from oxidative stress in Saccharomyces cerevisiae. PLoS One. 2020;15(2):e0229103 Authors: Endres L, Rose RE, Doyle F, Rahn T, Lee B, Seaman J, McIntyre WD, Fabris D Abstract Chemical modifications that regulate protein expression at the translational level are emerging as vital components of the cellular stress response. Transfer RNAs (tRNAs) are significant targets for methyl-based modifications, which are catalyzed by tRNA methyltransferases (Trms). Here, Saccharomyces cerevisiae served as a model eukaryote system to investigate the role of 2'-O-ribose tRNA methylation in the cell's response to oxidative stress. Using 2'-O-ribose deletion mutants for trms 3, 7, 13, and 44, in acute and chronic exposure settings, we demonstrate a broad cell sensitivity to oxidative stress-inducing toxicants (i.e., hydrogen peroxide, rotenone, and acetic acid). A global analysis of hydrogen peroxide-induced tRNA modifications shows a complex profile of decreased, or undetectable, 2'-O-ribose modification events in 2'-O-ribose trm mutant strains, providing a critical link between this type of modification event and Trm status post-exposure. Based on the pronounced oxidative stress sensitivity observed for trm7 mutants, we used a bioinformatic tool to identify transcripts as candidates for regulation by Trm7-catalyzed modifications (i.e., enriched in UUC codons decoded by tRNAPheGmAA). This screen identified transcripts linked to diverse biological processes that promote cellular recovery after oxidative stress exposure, including DNA repair, chromatin remodeling, and nutrient acquisition (i.e., CRT10, HIR3, HXT2, and GNP1); moreover, these mutants were also oxidative stress-sensitive. Together, these results solidify a role for TRM3, 7, 13, and 44, in the cellular response to oxidative stress, and implicate 2'-O-ribose tRNA modification as an epitranscriptomic strategy for oxidative stress recovery. PMID: 32053677 [PubMed - in process]

Related Articles Effects of scion/rootstock combination on flavor quality of orange juice from Huanglongbing (HLB) -affected trees: a two-year study of the targeted metabolomics. J Agric Food Chem. 2020 Feb 13;: Authors: Huang L, Grosser JW, Gmitter FG, Sims CA, Wang Y Abstract The bacterial disease Huanglongbing (HLB) has been causing large economic losses in the citrus industry worldwide. Aimed at unravelling the mechanisms of scion/rootstock combination on improving HLB-affected orange juice quality, a specific scion/rootstock combination field trial was designed using three sibling rootstocks and two late maturing sweet orange scion cultivars. Scion/rootstock combination significantly improved the overall consumer liking of orange juice from the trees, all of which were affected by HLB. Using a three-way ANOVA assay, rootstocks showed significant effects on the consumer liking and overall flavor, while scions had significant effects on the freshness and overall orange flavor intensity of the juice. A PLS-DA model combined with KEGG pathway enrichment analysis and some biomarker metabolites further indicated that scions mainly affected metabolism of alanine, aspartate and glutamate in orange fruit. Meanwhile, rootstocks had an impact on the biosynthetic pathways of secondary metabolites, especially the flavonoids biosynthesis with diosmin, narirutin and rutin involved. Sugars and organic acids were not closely correlated with the overall liking and sensory perception of orange juice. Rather, flavonoids such as diosmin and hesperidin, terpenoids such as limonin and nomilin, and volatile aromas played important roles in improving consumer overall liking. These results indicated that an optimum tolerant scion/rootstock combination can make a positive contribution towards improved fruit or juice quality from HLB-affected citrus trees and enabled a better understanding of fruit quality improvement based on scion and rootstock combinations. PMID: 32052973 [PubMed - as supplied by publisher]

Related Articles Comparative lipidomic analysis of inflammatory mediators in the aqueous humor and tear fluid of humans and rabbits. Metabolomics. 2020 Feb 12;16(2):27 Authors: Chistyakov DV, Azbukina NV, Astakhova AA, Goriainov SV, Chistyakov VV, Tiulina VV, Baksheeva VE, Kotelin VI, Fedoseeva EV, Zamyatnin AA, Philippov PP, Kiseleva OA, Bessmertny AM, Senin II, Iomdina EN, Sergeeva MG, Zernii EY Abstract INTRODUCTION: Ocular inflammation is a key pathogenic factor in most blindness-causing visual disorders. It can manifest in the aqueous humor (AH) and tear fluid (TF) as alterations in polyunsaturated fatty acids (PUFAs) and their metabolites, oxylipins, lipid mediators, which are biosynthesized via enzymatic pathways involving lipoxygenase, cyclooxygenase or cytochrome P450 monooxygenase and specifically regulate inflammation and resolution pathways. OBJECTIVES: This study aimed to establish the baseline patterns of PUFAs and oxylipins in AH and TF by their comprehensive lipidomic identification and profiling in humans in the absence of ocular inflammation and comparatively analyze these compounds in the eye liquids of rabbits, the species often employed in investigative ophthalmology. METHODS: Ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used for qualitative and quantitative characterization of lipid compounds in the analyzed samples. RESULTS: A total of 28 lipid compounds were identified, including phospholipid derivatives and PUFAs, as well as 22 oxylipins. Whereas the PUFAs included arachidonic, docosahexaenoic and eicosapentaenoic acids, the oxylipins were derived mainly from arachidonic, linoleic and α-linolenic acids. Remarkably, although the concentration of oxylipins in AH was lower compared to TF, these liquids showed pronounced similarity in their lipid profiles, which additionally exhibited noticeable interspecies concordance. CONCLUSION: The revealed correlations confirm the feasibility of rabbit models for investigating pathogenesis and trialing therapies of human eye disorders. The identified metabolite patterns suggest enzymatic mechanisms of oxylipin generation in AH and TF and might be used as a reference in ocular inflammation studies. PMID: 32052201 [PubMed - in process]

Related Articles Targeted metabolomics of CSF in healthy individuals and patients with secondary progressive multiple sclerosis using high-resolution mass spectrometry. Metabolomics. 2020 Feb 12;16(2):26 Authors: Carlsson H, Abujrais S, Herman S, Khoonsari PE, Åkerfeldt T, Svenningsson A, Burman J, Kultima K Abstract INTRODUCTION: Standardized commercial kits enable targeted metabolomics analysis and may thus provide an attractive complement to the more explorative approaches. The kits are typically developed for triple quadrupole mass spectrometers using serum and plasma. OBJECTIVES: Here we measure the concentrations of preselected metabolites in cerebrospinal fluid (CSF) using a kit developed for high-resolution mass spectrometry (HRMS). Secondarily, the study aimed to investigate metabolite alterations in patients with secondary progressive multiple sclerosis (SPMS) compared to controls. METHODS: We performed targeted metabolomics in human CSF on twelve SPMS patients and twelve age and sex-matched healthy controls using the Absolute IDQ-p400 kit (Biocrates Life Sciences AG) developed for HRMS. The extracts were analysed using two methods; liquid chromatography-mass spectrometry (LC-HRMS) and flow injection analysis-MS (FIA-HRMS). RESULTS: Out of 408 targeted metabolites, 196 (48%) were detected above limit of detection and 35 were absolutely quantified. Metabolites analyzed using LC-HRMS had a median coefficient of variation (CV) of 3% and 2.5% between reinjections the same day and after prolonged storage, respectively. The corresponding results for the FIA-HRMS were a median CV of 27% and 21%, respectively. We found significantly (p < 0.05) elevated levels of glycine, asymmetric dimethylarginine (ADMA), glycerophospholipid PC-O (34:0) and sum of hexoses in SPMS patients compared to controls. CONCLUSION: The Absolute IDQ-p400 kit could successfully be used for quantifying targeted metabolites in the CSF. Metabolites quantified using LC-HRMS showed superior reproducibility compared to FIA-HRMS. PMID: 32052189 [PubMed - in process]

Related Articles Author Correction: Metabolomics reveals perturbations in endometrium and serum of minimal and mild endometriosis. Sci Rep. 2020 Feb 12;10(1):2790 Authors: Dutta M, Singh B, Joshi M, Das D, Subramani E, Maan M, Jana SK, Sharma U, Das S, Dasgupta S, Ray CD, Chakravarty B, Chaudhury K Abstract An amendment to this paper has been published and can be accessed via a link at the top of the paper. PMID: 32051518 [PubMed - in process]

Related Articles Toxic tall fescue grazing increases susceptibility of the Angus steer fecal microbiota and plasma/urine metabolome to environmental effects. Sci Rep. 2020 Feb 12;10(1):2497 Authors: Mote RS, Hill NS, Skarlupka JH, Tran VT, Walker DI, Turner ZB, Sanders ZP, Jones DP, Suen G, Filipov NM Abstract Impaired thermoregulation and lowered average daily gains (ADG) result when livestock graze toxic endophyte (Epichloë coenophialum)-infected tall fescue (E+) and are hallmark signs of fescue toxicosis (FT), a disease exacerbated by increased temperature and humidity (+temperature-humidity index; +THI). We previously reported FT is associated with metabolic and microbiota perturbations under thermoneutral conditions; here, we assessed the influence of E+ grazing and +THI on the microbiota:metabolome interactions. Using high-resolution metabolomics and 16S rRNA gene sequencing, plasma/urine metabolomes and the fecal microbiota of Angus steers grazing non-toxic or E+ tall fescue were evaluated in the context of +THI. E+ grazing affected the fecal microbiota profile; +THI conditions modulated the microbiota only in E+ steers. E+ also perturbed many metabolic pathways, namely amino acid and inflammation-related metabolism; +THI affected these pathways only in E+ steers. Integrative analyses revealed the E+ microbiota correlated and co-varied with the metabolomes in a THI-dependent manner. Operational taxonomic units in the families Peptococcaceae, Clostridiaceae, and Ruminococcaceae correlated with production parameters (e.g., ADG) and with multiple plasma/urine metabolic features, providing putative FT biomarkers and/or targets for the development of FT therapeutics. Overall, this study suggests that E+ grazing increases Angus steer susceptibility to +THI, and offers possible targets for FT interventions. PMID: 32051515 [PubMed - in process]

Related Articles Dysregulated metabolic pathways in age-related macular degeneration. Sci Rep. 2020 Feb 12;10(1):2464 Authors: Zhang M, Jiang N, Chu Y, Postnikova O, Varghese R, Horvath A, Cheema AK, Golestaneh N Abstract Age-related macular degeneration is a major cause of vision impairment in the Western world among people of 55 years and older. Recently we have shown that autophagy is dysfunctional in the retinal pigment epithelium (RPE) of the AMD donor eyes (AMD RPE). We also showed increased reactive oxygen (ROS) production, increased cytoplasmic glycogen accumulation, mitochondrial dysfunction and disintegration, and enlarged and annular LAMP-1-positive organelles in AMD RPE. However, the underlying mechanisms inducing these abnormalities remain to be elucidated. Here, by performing a comprehensive study, we show increased PAPR2 expression, deceased NAD+, and SIRT1, increased PGC-1α acetylation (inactive form), lower AMPK activity, and overactive mTOR pathway in AMD RPE as compared to normal RPE. Metabolomics and lipidomics revealed dysregulated metabolites in AMD RPE as compared to normal RPE, including glycerophospholipid metabolism, involved in autophagy, lipid, and protein metabolisms, glutathione, guanosine, and L-glutamic acid, which are implicated in protection against oxidative stress and neurotoxicity, further supporting our observations. Our data show dysregulated metabolic pathways as important contributors to AMD pathophysiology, and facilitate the development of new treatment strategies for this debilitating disease of the visual system. PMID: 32051464 [PubMed - in process]

Related Articles Elevated plasma β-hydroxybutyrate predicts adverse outcomes and disease progression in patients with arrhythmogenic cardiomyopathy. Sci Transl Med. 2020 Feb 12;12(530): Authors: Song JP, Chen L, Chen X, Ren J, Zhang NN, Tirasawasdichai T, Hu ZL, Hua W, Hu YR, Tang HR, Chen HV, Hu SS Abstract Sudden death could be the first symptom of patients with arrhythmogenic cardiomyopathy (AC), a disease for which clinical indicators predicting adverse progression remain lacking. Recent findings suggest that metabolic dysregulation is present in AC. We performed this study to identify metabolic indicators that predicted major adverse cardiac events (MACEs) in patients with AC and their relatives. Comparing explanted hearts from patients with AC and healthy donors, we identified deregulated metabolic pathways using quantitative proteomics. Right ventricles (RVs) from patients with AC displayed elevated ketone metabolic enzymes, OXCT1 and HMGCS2, suggesting higher ketone metabolism in AC RVs. Analysis of matched coronary artery and sinus plasma suggested potential ketone body synthesis at early-stage AC, which was validated using patient-derived induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) in vitro. Targeted metabolomics analysis in RVs from end-stage AC revealed a "burned-out" state, with predominant medium-chain fatty acid rather than ketone body utilization. In an independent validation cohort, 65 probands with mostly non-heart failure manifestations of AC had higher plasma β-hydroxybutyrate (β-OHB) than 62 healthy volunteers (P < 0.001). Probands with AC with MACE had higher β-OHB than those without MACE (P < 0.001). Among 94 relatives of probands, higher plasma β-OHB distinguished 25 relatives having suspected AC from nonaffected relatives. This study demonstrates that elevated plasma β-OHB predicts MACE in probands and disease progression in patients with AC and their clinically asymptomatic relatives. PMID: 32051229 [PubMed - in process]

Related Articles A century-old mystery unveiled: Sekizaisou is a natural lignin mutant. Plant Physiol. 2020 Feb 12;: Authors: Yamamoto M, Tomiyama H, Koyama A, Okuizumi H, Liu S, Vanholme R, Goeminne G, Hirai Y, Shi H, Nuoendagula N, Takata N, Ikeda T, Uesugi M, Kim H, Sakamoto S, Mitsuda N, Boerjan WA, Ralph J, Kajita S PMID: 32051179 [PubMed - as supplied by publisher]

Related Articles Self-reinoculation with fecal flora changes microbiota density and composition leading to an altered bile-acid profile in the mouse small intestine. Microbiome. 2020 Feb 12;8(1):19 Authors: Bogatyrev SR, Rolando JC, Ismagilov RF Abstract BACKGROUND: The upper gastrointestinal tract plays a prominent role in human physiology as the primary site for enzymatic digestion and nutrient absorption, immune sampling, and drug uptake. Alterations to the small intestine microbiome have been implicated in various human diseases, such as non-alcoholic steatohepatitis and inflammatory bowel conditions. Yet, the physiological and functional roles of the small intestine microbiota in humans remain poorly characterized because of the complexities associated with its sampling. Rodent models are used extensively in microbiome research and enable the spatial, temporal, compositional, and functional interrogation of the gastrointestinal microbiota and its effects on the host physiology and disease phenotype. Classical, culture-based studies have documented that fecal microbial self-reinoculation (via coprophagy) affects the composition and abundance of microbes in the murine proximal gastrointestinal tract. This pervasive self-reinoculation behavior could be a particularly relevant study factor when investigating small intestine microbiota. Modern microbiome studies either do not take self-reinoculation into account, or assume that approaches such as single housing mice or housing on wire mesh floors eliminate it. These assumptions have not been rigorously tested with modern tools. Here, we used quantitative 16S rRNA gene amplicon sequencing, quantitative microbial functional gene content inference, and metabolomic analyses of bile acids to evaluate the effects of self-reinoculation on microbial loads, composition, and function in the murine upper gastrointestinal tract. RESULTS: In coprophagic mice, continuous self-exposure to the fecal flora had substantial quantitative and qualitative effects on the upper gastrointestinal microbiome. These differences in microbial abundance and community composition were associated with an altered profile of the small intestine bile acid pool, and, importantly, could not be inferred from analyzing large intestine or stool samples. Overall, the patterns observed in the small intestine of non-coprophagic mice (reduced total microbial load, low abundance of anaerobic microbiota, and bile acids predominantly in the conjugated form) resemble those typically seen in the human small intestine. CONCLUSIONS: Future studies need to take self-reinoculation into account when using mouse models to evaluate gastrointestinal microbial colonization and function in relation to xenobiotic transformation and pharmacokinetics or in the context of physiological states and diseases linked to small intestine microbiome and to small intestine dysbiosis. Video abstract. PMID: 32051033 [PubMed - in process]

Related Articles Gut Microbiota is the Key to the Antidepressant Effect of Chaihu-Shu-Gan-San. Metabolites. 2020 Feb 10;10(2): Authors: Yu M, Jia HM, Zhang T, Shang H, Zhang HW, Ma LY, Zou ZM Abstract Accumulating evidence highlights the link between gut microbiota and depression. As an antidepressant herbal drug in clinic, Chaihu-Shu-Gan-San (CSGS) has also been used in China for the treatment of various gastrointestinal disorders. Therefore, we hypothesize that the gut microbiota might be involved in the effect of CSGS. Here, we investigated the antidepressant effects of CSGS against chronic variable stress (CVS)-induced depression rats with and without antibiotic treatment using 16S rRNA gene sequencing and ultra-performance liquid chromatography coupled with time of flight mass spectrometry (UPLC-Q-TOF/MS) based metabolome approaches. As a result, the prominent effects of CSGS against the depression-like behavioral disorder of CVS-induced rats were significantly weakened when the gut microbiota was changed after oral administration of the broad-spectrum antibiotic. The mediation of CSGS on hippocampal levels of serotonin (5-HT) and glutamic acid (Glu) was also receded with the antibiotic treatment. Further investigation on the diversity of microbiome indicated that the improvement effect of CSGS on gut microbiota dysbiosis-especially the phylum level of Firmicutes-was attenuated compared with the CSGS combined antibiotic treated one. Moreover, 3-hydroxypicolinic acid (H4) and inosine (H8) in the hippocampus were considered as important biomarkers for depression and are also associated with gut microbiota mediated CSGS efficacy. Taken together, our current study indicated that gut microbiota is a critical factor in the antidepressant effect of CSGS, and this acts in part through gut microbiota to improve depression-related biomarkers. PMID: 32050718 [PubMed]

Related Articles Combination of Hypoglycemia and Metformin Impairs Tumor Metabolic Plasticity and Growth by Modulating the PP2A-GSK3β-MCL-1 Axis. Cancer Cell. 2019 05 13;35(5):798-815.e5 Authors: Elgendy M, Cirò M, Hosseini A, Weiszmann J, Mazzarella L, Ferrari E, Cazzoli R, Curigliano G, DeCensi A, Bonanni B, Budillon A, Pelicci PG, Janssens V, Ogris M, Baccarini M, Lanfrancone L, Weckwerth W, Foiani M, Minucci S Abstract Tumor cells may adapt to metabolic challenges by alternating between glycolysis and oxidative phosphorylation (OXPHOS). To target this metabolic plasticity, we combined intermittent fasting, a clinically feasible approach to reduce glucose availability, with the OXPHOS inhibitor metformin. In mice exposed to 24-h feeding/fasting cycles, metformin impaired tumor growth only when administered during fasting-induced hypoglycemia. Synergistic anti-neoplastic effects of the metformin/hypoglycemia combination were mediated by glycogen synthase kinase 3β (GSK3β) activation downstream of PP2A, leading to a decline in the pro-survival protein MCL-1, and cell death. Mechanistically, specific activation of the PP2A-GSK3β axis was the sum of metformin-induced inhibition of CIP2A, a PP2A suppressor, and of upregulation of the PP2A regulatory subunit B56δ by low glucose, leading to an active PP2A-B56δ complex with high affinity toward GSK3β. PMID: 31031016 [PubMed - indexed for MEDLINE]

23 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/13PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

19 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/12PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/11PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Related Articles Environmental exposure of northern pike to a primary wastewater effluent: Impact on the lipidomic profile and lipid metabolism. Aquat Toxicol. 2020 Jan 25;221:105421 Authors: Dépatie C, Houde M, Verreault J Abstract Lipids play important roles in growth, reproduction, locomotion, and migration of fish. Municipal effluents, which are complex mixtures of biological and chemical compounds including flame retardants, have been shown to alter lipid metabletabolism in environmentally and experimentally exposed fish. Down-regulation of several genes coding for fatty acid metabolism enzymes has previously been reported in male northern pike (Esox lucius) collected in the St. Lawrence River (QC, Canada) downstream of a major primary wastewater treatment plant (WWTP) point of discharge. The main objective of this study was to investigate the effects of exposure to the Montreal's WWTP effluent on the lipidomic profile (i.e., fatty acids, acylcarnitines, and phospholipids) as well as the transcription of genes related to lipid metabolism in the liver of northern pike collected upstream and downstream of this WWTP effluent. Halogenated flame retardant concentrations were also determined in pike liver and used as markers of exposure to this effluent. Greater concentrations of saturated and monounsaturated lysophosphatidylcholines (LPCs) and lower concentrations of polyunsaturated LPCs were determined in the liver of pike collected downstream of the WWTP compared to those collected upstream. Lower mRNA levels of peroxisome proliferator-activated receptor alpha (pparα), a major regulator of lipid metabolism, were also measured in pike exposed to Montreal's WWTP effluent. In addition, the relative contributions (%) of LPC 18:2 and LPC14:0, compounds used as markers of obesity and inflammation, were significantly correlated with halogenated flame retardant concentrations and fish girth. Results of the present study suggest that chronic environmental exposure to a primary WWTP effluent can modulate the transcription of genes related to lipid metabolism, and hence affect the hepatic phospholipid composition of pike from the St. Lawrence River. PMID: 32036233 [PubMed - as supplied by publisher]