PubMed

The dilemma of diagnosing coenzyme Q10 deficiency in muscle. Mol Genet Metab. 2018 Feb 23;: Authors: Louw R, Smuts I, Wilsenach KL, Jonck LM, Schoonen M, van der Westhuizen FH Abstract BACKGROUND: Coenzyme Q10 (CoQ10) is an important component of the mitochondrial respiratory chain (RC) and is critical for energy production. Although the prevalence of CoQ10 deficiency is still unknown, the general consensus is that the condition is under-diagnosed. The aim of this study was to retrospectively investigate CoQ10 deficiency in frozen muscle specimens in a cohort of ethnically diverse patients who received muscle biopsies for the investigation of a possible RC deficiency (RCD). METHODS: Muscle samples were homogenized whereby 600 ×g supernatants were used to analyze RC enzyme activities, followed by quantification of CoQ10 by stable isotope dilution liquid chromatography tandem mass spectrometry. The experimental group consisted of 156 patients of which 76 had enzymatically confirmed RCDs. To further assist in the diagnosis of CoQ10 deficiency in this cohort, we included sequencing of 18 selected nuclear genes involved with CoQ10 biogenesis in 26 patients with low CoQ10 concentration in muscle samples. RESULTS: Central 95% reference intervals (RI) were established for CoQ10 normalized to citrate synthase (CS) or protein. Nine patients were considered CoQ10 deficient when expressed against CS, while 12 were considered deficient when expressed against protein. In two of these patients the molecular genetic cause could be confirmed, of which one would not have been identified as CoQ10 deficient if expressed only against protein content. CONCLUSION: In this retrospective study, we report a central 95% reference interval for 600 ×g muscle supernatants prepared from frozen samples. The study reiterates the importance of including CoQ10 quantification as part of a diagnostic approach to study mitochondrial disease as it may complement respiratory chain enzyme assays with the possible identification of patients that may benefit from CoQ10 supplementation. However, the anomaly that only a few patients were identified as CoQ10 deficient against both markers (CS and protein), while the majority of patients where only CoQ10 deficient against one of the markers (and not the other), remains problematic. We therefore conclude from our data that, to prevent possibly not diagnosing a potential CoQ10 deficiency, the expression of CoQ10 levels in muscle on both CS as well as protein content should be considered. PMID: 29530532 [PubMed - as supplied by publisher]

Exosomal αvβ6 integrin is required for monocyte M2 polarization in prostate cancer. Matrix Biol. 2018 Mar 09;: Authors: Lu H, Bowler N, Harshyne LA, Craig Hooper D, Krishn SR, Kurtoglu S, Fedele C, Liu Q, Tang HY, Kossenkov AV, Kelly WK, Wang K, Kean RB, Weinreb PH, Yu L, Dutta A, Fortina P, Ertel A, Stanczak M, Forsberg F, Gabrilovich DI, Speicher DW, Altieri DC, Languino LR Abstract Therapeutic approaches aimed at curing prostate cancer are only partially successful given the occurrence of highly metastatic resistant phenotypes that frequently develop in response to therapies. Recently, we have described αvβ6, a surface receptor of the integrin family as a novel therapeutic target for prostate cancer; this epithelial-specific molecule is an ideal target since, unlike other integrins, it is found in different types of cancer but not in normal tissues. We describe a novel αvβ6-mediated signaling pathway that has profound effects on the microenvironment. We show that αvβ6 is transferred from cancer cells to monocytes, including β6-/- monocytes, by exosomes and that monocytes from prostate cancer patients, but not from healthy volunteers, express αvβ6. Cancer cell exosomes, purified via density gradients, promote M2 polarization, whereas αvβ6 down-regulation in exosomes inhibits M2 polarization in recipient monocytes. Also, as evaluated by our proteomic analysis, αvβ6 down-regulation causes a significant increase in donor cancer cells, and their exosomes, of two molecules that have a tumor suppressive role, STAT1 and MX1/2. Finally, using the Ptenpc-/- prostate cancer mouse model, which carries a prostate epithelial-specific Pten deletion, we demonstrate that αvβ6 inhibition in vivo causes up-regulation of STAT1 in cancer cells. Our results provide evidence of a novel mechanism that regulates M2 polarization and prostate cancer progression through transfer of αvβ6 from cancer cells to monocytes through exosomes. PMID: 29530483 [PubMed - as supplied by publisher]

MassImager: A software for interactive and in-depth analysis of mass spectrometry imaging data. Anal Chim Acta. 2018 Jul 26;1015:50-57 Authors: He J, Huang L, Tian R, Li T, Sun C, Song X, Lv Y, Luo Z, Li X, Abliz Z Abstract Mass spectrometry imaging (MSI) has become a powerful tool to probe molecule events in biological tissue. However, it is a widely held viewpoint that one of the biggest challenges is an easy-to-use data processing software for discovering the underlying biological information from complicated and huge MSI dataset. Here, a user-friendly and full-featured MSI software including three subsystems, Solution, Visualization and Intelligence, named MassImager, is developed focusing on interactive visualization, in-situ biomarker discovery and artificial intelligent pathological diagnosis. Simplified data preprocessing and high-throughput MSI data exchange, serialization jointly guarantee the quick reconstruction of ion image and rapid analysis of dozens of gigabytes datasets. It also offers diverse self-defined operations for visual processing, including multiple ion visualization, multiple channel superposition, image normalization, visual resolution enhancement and image filter. Regions-of-interest analysis can be performed precisely through the interactive visualization between the ion images and mass spectra, also the overlaid optical image guide, to directly find out the region-specific biomarkers. Moreover, automatic pattern recognition can be achieved immediately upon the supervised or unsupervised multivariate statistical modeling. Clear discrimination between cancer tissue and adjacent tissue within a MSI dataset can be seen in the generated pattern image, which shows great potential in visually in-situ biomarker discovery and artificial intelligent pathological diagnosis of cancer. All the features are integrated together in MassImager to provide a deep MSI processing solution at the in-situ metabolomics level for biomarker discovery and future clinical pathological diagnosis. PMID: 29530251 [PubMed - in process]

Serum proton NMR metabolomics analysis of human lung cancer following microwave ablation. Radiat Oncol. 2018 Mar 12;13(1):40 Authors: Hu JM, Sun HT Abstract BACKGROUND: To find potential serum biomarkers of microwave ablation (MWA) for treatment of human lung cancer by 1H nuclear magnetic resonance (NMR)-based metabolomics analysis. METHODS: Serum specimens collected from 43 healthy individuals, 39 patients with advanced non-small cell lung cancer (NSCLC) and 38 NSCLC patients treated with MWA, were subjected to 1H NMR-based metabolomics analysis. Partial least squares discriminant analysis was used to analyze the data. RESULTS: Compared with healthy controls, NSCLC patients showed significantly elevated serum levels of lactate, alanine, glutamate, proline, glycoprotein, phenylalanine, tyrosine and tryptophan, and markedly decreased serum levels of glucose, taurine, glutamine, glycine, phosphocreatine and threonine (p < 0.05). MWA treatment reversed the metabolic profiles of NSCLC patients towards the control group. CONCLUSIONS: 1H NMR-based metabolomics analysis enhanced the current understanding of the mechanisms involved in NSCLC, and uncovered the therapeutic potential of MWA for treatment of NSCLC. The above disturbed serum metabolites were proposed to be the potential biomarkers that may help to predict NSCLC and to evaluate the efficacy of MWA in the treatment of NSCLC. PMID: 29530051 [PubMed - in process]

Related Articles Novel Plasmodium falciparum metabolic network reconstruction identifies shifts associated with clinical antimalarial resistance. BMC Genomics. 2017 Jul 19;18(1):543 Authors: Carey MA, Papin JA, Guler JL Abstract BACKGROUND: Malaria remains a major public health burden and resistance has emerged to every antimalarial on the market, including the frontline drug, artemisinin. Our limited understanding of Plasmodium biology hinders the elucidation of resistance mechanisms. In this regard, systems biology approaches can facilitate the integration of existing experimental knowledge and further understanding of these mechanisms. RESULTS: Here, we developed a novel genome-scale metabolic network reconstruction, iPfal17, of the asexual blood-stage P. falciparum parasite to expand our understanding of metabolic changes that support resistance. We identified 11 metabolic tasks to evaluate iPfal17 performance. Flux balance analysis and simulation of gene knockouts and enzyme inhibition predict candidate drug targets unique to resistant parasites. Moreover, integration of clinical parasite transcriptomes into the iPfal17 reconstruction reveals patterns associated with antimalarial resistance. These results predict that artemisinin sensitive and resistant parasites differentially utilize scavenging and biosynthetic pathways for multiple essential metabolites, including folate and polyamines. Our findings are consistent with experimental literature, while generating novel hypotheses about artemisinin resistance and parasite biology. We detect evidence that resistant parasites maintain greater metabolic flexibility, perhaps representing an incomplete transition to the metabolic state most appropriate for nutrient-rich blood. CONCLUSION: Using this systems biology approach, we identify metabolic shifts that arise with or in support of the resistant phenotype. This perspective allows us to more productively analyze and interpret clinical expression data for the identification of candidate drug targets for the treatment of resistant parasites. PMID: 28724354 [PubMed - indexed for MEDLINE]

Related Articles Spatially resolved metabolic distribution for unraveling the physiological change and responses in tomato fruit using matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI). Anal Bioanal Chem. 2017 Feb;409(6):1697-1706 Authors: Nakamura J, Morikawa-Ichinose T, Fujimura Y, Hayakawa E, Takahashi K, Ishii T, Miura D, Wariishi H Abstract Information on spatiotemporal metabolic behavior is indispensable for a precise understanding of physiological changes and responses, including those of ripening processes and wounding stress, in fruit, but such information is still limited. Here, we visualized the spatial distribution of metabolites within tissue sections of tomato (Solanum lycopersicum L.) fruit using a matrix-assisted laser desorption/ionization-mass spectrometry imaging (MALDI-MSI) technique combined with a matrix sublimation/recrystallization method. This technique elucidated the unique distribution patterns of more than 30 metabolite-derived ions, including primary and secondary metabolites, simultaneously. To investigate spatiotemporal metabolic alterations during physiological changes at the whole-tissue level, MALDI-MSI was performed using the different ripening phenotypes of mature green and mature red tomato fruits. Although apparent alterations in the localization and intensity of many detected metabolites were not observed between the two tomatoes, the amounts of glutamate and adenosine monophosphate, umami compounds, increased in both mesocarp and locule regions during the ripening process. In contrast, malate, a sour compound, decreased in both regions. MALDI-MSI was also applied to evaluate more local metabolic responses to wounding stress. Accumulations of a glycoalkaloid, tomatine, and a low level of its glycosylated metabolite, esculeoside A, were found in the wound region where cell death had been induced. Their inverse levels were observed in non-wounded regions. Furthermore, the amounts of both compounds differed in the developmental stages. Thus, our MALDI-MSI technique increased the understanding of the physiological changes and responses of tomato fruit through the determination of spatiotemporally resolved metabolic alterations. Graphical abstract ᅟ. PMID: 27933363 [PubMed - indexed for MEDLINE]

Related Articles Metabolic profiling of ob/ob mouse fatty liver using HR-MAS 1H-NMR combined with gene expression analysis reveals alterations in betaine metabolism and the transsulfuration pathway. Anal Bioanal Chem. 2017 Feb;409(6):1591-1606 Authors: Gogiashvili M, Edlund K, Gianmoena K, Marchan R, Brik A, Andersson JT, Lambert J, Madjar K, Hellwig B, Rahnenführer J, Hengstler JG, Hergenröder R, Cadenas C Abstract Metabolic perturbations resulting from excessive hepatic fat accumulation are poorly understood. Thus, in this study, leptin-deficient ob/ob mice, a mouse model of fatty liver disease, were used to investigate metabolic alterations in more detail. Metabolites were quantified in intact liver tissues of ob/ob (n = 8) and control (n = 8) mice using high-resolution magic angle spinning (HR-MAS) 1H-NMR. In addition, after demonstrating that HR-MAS 1H-NMR does not affect RNA integrity, transcriptional changes were measured by quantitative real-time PCR on RNA extracted from the same specimens after HR-MAS 1H-NMR measurements. Importantly, the gene expression changes obtained agreed with those observed by Affymetrix microarray analysis performed on RNA isolated directly from fresh-frozen tissue. In total, 40 metabolites could be assigned in the spectra and subsequently quantified. Quantification of lactate was also possible after applying a lactate-editing pulse sequence that suppresses the lipid signal, which superimposes the lactate methyl resonance at 1.3 ppm. Significant differences were detected for creatinine, glutamate, glycine, glycolate, trimethylamine-N-oxide, dimethylglycine, ADP, AMP, betaine, phenylalanine, and uridine. Furthermore, alterations in one-carbon metabolism, supported by both metabolic and transcriptional changes, were observed. These included reduced demethylation of betaine to dimethylglycine and the reduced expression of genes coding for transsulfuration pathway enzymes, which appears to preserve methionine levels, but may limit glutathione synthesis. Overall, the combined approach is advantageous as it identifies changes not only at the single gene or metabolite level but also deregulated pathways, thus providing critical insight into changes accompanying fatty liver disease. Graphical abstract A Evaluation of RNA integrity before and after HR-MAS 1H-NMR of intact mouse liver tissue. B Metabolite concentrations and gene expression levels assessed in ob/ob (steatotic) and ob/+ (control) mice using HR-MAS 1H-NMR and qRT-PCR, respectively. PMID: 27896396 [PubMed - indexed for MEDLINE]

22 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 2018/03/13PubMed 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.

Metabolomics and its physiological regulation process reveal the salt-tolerant mechanism in Glycine soja seedling roots. Plant Physiol Biochem. 2018 Mar 05;126:187-196 Authors: Jiao Y, Bai Z, Xu J, Zhao M, Khan Y, Hu Y, Shi L Abstract Wild soybean (Glycine soja) is an excellent germplasm resource and has strong resistance and wide adaptability to different environments. Hence, the physiology and metabolomics characteristics of wild soybean under different types of salt stress were determined to improve understanding of salt-tolerant mechanisms of wild soybean in the field. Two types of wild soybean seedlings were exposed to two different types of salt stress for 14 d. The photosynthesis of wild soybean seedling extracts were analyzed using metabolomics based on gas chromatography-mass spectrometry. The wild soybean root extracts used metabolomics to quantify the metabolic changes and ion contents. The assimilative function of photosynthesis in salt-tolerant wild soybean was less inhibited than in common wild soybean, and it regulated accumulation of toxic ions and maintained the accumulation of K+ and Mg2+ to alleviate salt stress. Moreover, in resisting salt stress the salt-tolerant wild soybean has showed improved amino acid and carbohydrate and polyol metabolisms under neutral-salt stress and organic acid, amino acid and tricarboxylic acid metabolisms under alkali-salt stress. Our results provide valuable insights into the response of salt-tolerant wild soybean to two types of salt stress by linking stress-related physiological responses to changes in metabolites. PMID: 29525442 [PubMed - as supplied by publisher]

African horse sickness virus (AHSV) with a deletion of 77 amino acids in NS3/NS3a protein is not virulent and a safe promising AHS Disabled Infectious Single Animal (DISA) vaccine platform. Vaccine. 2018 Mar 07;: Authors: van Rijn PA, Maris-Veldhuis MA, Potgieter CA, van Gennip RGP Abstract African horse sickness virus (AHSV) is a virus species in the genus Orbivirus of the family Reoviridae. Currently, nine serotypes have been defined showing limited cross neutralization. AHSV is transmitted by species of Culicoides biting midges and causes African Horse Sickness (AHS) in equids with a mortality up to 95% in naïve domestic horses. AHS has become a serious threat for countries outside Africa, since endemic Culicoides species in moderate climates are competent vectors of closely related bluetongue virus. AHS outbreaks cause huge economic losses in developing countries. In the developed world, outbreaks will result in losses in the equestrian industry and will have an enormous emotional impact on owners of pet horses. Live-attenuated vaccine viruses (LAVs) have been developed, however, safety of these LAVs are questionable due to residual virulence, reversion to virulence, and risk on virulent variants by reassortment between LAVs or with field AHSV. Research aims vaccines with improved profiles. Reverse genetics has recently being developed for AHSV and has opened endless possibilities including development of AHS vaccine candidates, such as Disabled Infectious Single Animal (DISA) vaccine. Here, virulent AHSV5 was recovered and its high virulence was confirmed by experimental infection of ponies. 'Synthetically derived' virulent AHSV5 with an in-frame deletion of 77 amino acids codons in genome segment 10 encoding NS3/NS3a protein resulted in similar in vitro characteristics as published NS3/NS3a knockout mutants of LAV strain AHSV4LP. In contrast to its highly virulent ancestor virus, this deletion AHSV5 mutant (DISA5) was completely safe for ponies. Two vaccinations with DISA5 as well as two vaccinations with DISA vaccine based on LAV strain AHSV4LP showed protection against lethal homologous AHSV. More research is needed to further improve efficacy, to explore the AHS DISA vaccine platform for all nine serotypes, and to study the vaccine profile in more detail. PMID: 29525278 [PubMed - as supplied by publisher]

Metabolomics analysis of 'Housui' Japanese pear flower buds during endodormancy reveals metabolic suppression by thermal fluctuation. Plant Physiol Biochem. 2018 Mar 02;126:134-141 Authors: Horikoshi HM, Sekozawa Y, Kobayashi M, Saito K, Kusano M, Sugaya S Abstract Dormancy is a complex phenomenon that allows plants to survive the winter season. Studies of dormancy have recently attracted more attention due to the expansion of temperate fruit production in areas under mild winters and due to climate changes. This study aimed to identify and characterize the metabolic changes induced by chilling temperatures, as well as during thermal fluctuation conditions that simulate mild winter and/or climate change scenarios. To do this, we compared the metabolic profile of Japanese pear flower buds exposed to constant chilling at 6 °C and thermal fluctuations of 6 °C/18 °C (150 h/150 h) during endodormancy. We detected 91 metabolites by gas chromatography paired with time-of-flight mass spectrometry (GC-TOF-MS) that could be classified into eight groups: amino acids, amino acid derivatives, organic acids, sugars and polyols, fatty acids and sterols, phenol lipids, phenylpropanoids, and other compounds. Metabolomics analysis revealed that the level of several amino acids decreased during endodormancy. Sugar and polyol levels increased during endodormancy during constant chilling and might be associated with chilling stress tolerance and providing an energy supply for resuming growth. In contrast, thermal fluctuations produced low levels of metabolites related to the pentose phosphate pathway, energy production, and tricarboxylic acid (TCA) cycle in flower buds, which may be associated with failed endodormancy release. This metabolic profile contributes to our understanding of the biological mechanism of dormancy during chilling accumulation and clarifies the metabolic changes during mild winters and future climate change scenarios. PMID: 29524800 [PubMed - as supplied by publisher]

Metabolomics-assisted metabolite profiling of itraconazole in human liver preparations. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Mar 07;1083:68-74 Authors: Kim JH, Choi WG, Moon JY, Lee JY, Lee S, Lee HS Abstract Itraconazole (ITZ) is a first-generation triazole-containing antifungal agent that effectively treats various fungal infections. As ITZ has a better safety profile than that of ketoconazole (KCZ), ITZ has been used worldwide for over 25 years. However, few reports have explored the metabolic profile of ITZ, and the underlying mechanism of ITZ-induced liver injury is not clearly understood. In the present study, we revisited ITZ metabolism in humans, using a non-targeted metabolomics approach, and identified several novel metabolic pathways including O-dearylation, piperazine oxidation, and piperazine-N,N'-deethylation. Furthermore, we explored the formation of reactive ITZ metabolites using trapping agents as surrogates, to assess the possibility of metabolism-mediated toxicity. We found that ITZ and its metabolites did not form any adducts with nucleophiles including glutathione, potassium cyanide, and semicarbazide. The present study expands our knowledge of ITZ metabolism and supports the suggestion that ITZ has a better safety profile than that of KCZ in terms of metabolism-mediated toxicity. PMID: 29524695 [PubMed - as supplied by publisher]

Gut microbiota mediates diurnal variation of acetaminophen induced acute liver injury in mice. J Hepatol. 2018 Mar 07;: Authors: Gong S, Lan T, Zeng L, Luo H, Yang X, Li N, Chen X, Liu Z, Li R, Win S, Liu S, Zhou H, Schnabl B, Jiang Y, Kaplowitz N, Chen P Abstract BACKGROUND & AIMS: Acetaminophen (APAP) induced hepatotoxicity is a leading cause of acute liver failure worldwide. It is well established that the liver damage induced by acetaminophen exhibits diurnal variation. However, the detailed mechanism for the hepatotoxic variation is not clear. Here we aimed to determine the relative contributions of gut microbiota in modulating the diurnal variation of hepatotoxicity induced by APAP. METHODS: Male Balb/C mice were treated with or without antibiotics and orally administrated a single dose of APAP (300 mg/kg) at ZT0 (when the light is on-start of resting period) and ZT12 (when the light is off-start of active period). RESULTS: In agreement with previous findings, hepatic injury was markedly enhanced at ZT12 compared with ZT0. Interestingly, upon antibiotics treatment, ZT12 displayed protection against APAP hepatotoxicity similar to ZT0. Moreover, mice that received the cecal content from ZT12 showed more severe liver damage than mice that received the cecal content from ZT0. 16S sequencing data revealed significant differences in the cecal content between ZT0 and ZT12 in the compositional level. Furthermore, metabolomic analysis showed that the gut microbial metabolites were also different between ZT0 and ZT12. Specifically, the level of 1-phenyl-1,2-propanedione (PPD) was significantly higher at ZT12 than ZT0. Treatment with PPD alone did not cause obvious liver damage. However, PPD synergistically enhanced APAP induced hepatic injury in vivo and in vitro. Finally, we found Saccharomyces cerevisiae, which could reduce intestinal PPD levels, was able to markedly alleviate APAP induced liver damage at ZT12. CONCLUSIONS: The gut microbial metabolite, 1-phenyl-1,2-propanedione was responsible, at least in part, for the diurnal variation of hepatotoxicity induced by APAP by decreasing GSH levels. LAY SUMMARY: Acetaminophen (APAP) induced acute liver failure due to over dose is a leading public health problem. APAP induced liver injury exhibited diurnal variation, in particular, it causes more severe liver damage when taken at night compared with that in the morning. Here we showed that gut microbial metabolite, 1-phenyl-1,2-propanedione (PPD) is involved in the rhythmic hepatotoxicity induced by APAP by depleting hepatic GSH levels. Our data suggest gut microbiota may be a potential target for reducing APAP induced acute liver injury. PMID: 29524531 [PubMed - as supplied by publisher]

Metabololipidomic profiling of functional immunoresolvent clusters and eicosanoids in mammalian tissues. Biochem Biophys Res Commun. 2018 Mar 07;: Authors: Norris PC, Serhan CN Abstract Metabolomics enables a systems approach to interrogate the bioactive mediators, their pathways and further metabolites involved in the physiology and pathophysiology of human and animal tissues. New metabololipidomic approaches with mass spectrometry presented in this brief review can now be utilized for the identification and profiling of lipid mediator networks that control inflammation-resolution in human blood and healthy and diseased solid tissues. Coagulation of blood is a protective response that prevents excessive bleeding on injury of blood vessels. Here, we review novel approaches to understand the relationship(s) between coagulation and resolution of inflammation and infection. To determine whether coagulation is involved in host-protective actions by lipid mediators, we used a metabololipidomic-based profiling approach with human whole blood (WB) during coagulation. We identified recently temporal clusters of endogenously produced pro-thrombotic and proinflammatory lipid mediators (eicosanoids), as well as specialized proresolving mediators (SPMs) in this vital process. In addition to the classic eicosanoids (prostaglandins, thromboxanes and leukotrienes), a specific SPM cluster was identified that consists of resolvin E1 (RvE1), RvD1, RvD5, lipoxin B4, and maresin 1, each of which present at bioactive concentrations (0.1-1 nM). The removal of adenosine from coagulating blood samples significantly enhances SPM amounts and unleashes the biosynthesis of RvD3, RvD4, and RvD6 evident following rapid snap freezing with centrifugation before extraction and LC-MS-MS. The classic cyclooxygenase inhibitors, celecoxib and indomethacin, that block thromboxanes and prostanoids do not block production of the clot-driven SPM cluster. Unbiased mass cytometry analysis demonstrated that the SPM cluster produced in human blood targets leukocytes at the single-cell level, directly activating extracellular signaling in human neutrophils and monocytes. Human whole blood treated with the components of this SPM cluster enhanced both phagocytosis and killing of Escherichia coli by leukocytes. Thus, we identified a pro-resolving lipid mediator circuit and specific SPM cluster that promotes host defense. This new lipid mediator (LM)-SPM metabololipidomic approach now provides accessible metabolomic profiles in healthy and diseased human tissues, including cancer, for precision and personalized medicine. PMID: 29524409 [PubMed - as supplied by publisher]

Related Articles Focus on fatty acids in the neurometabolic pathophysiology of psychiatric disorders. J Inherit Metab Dis. 2018 Mar 09;: Authors: Mocking RJT, Assies J, Ruhé HG, Schene AH Abstract Continuous research into the pathophysiology of psychiatric disorders, such as major depressive disorder (MDD), posttraumatic stress disorder (PTSD), and schizophrenia, suggests an important role for metabolism. This narrative review will provide an up-to-date summary of how metabolism is thought to be involved in the pathophysiology of these psychiatric disorders. We will focus on (I) the important role of fatty acids in these metabolic alterations, (II) whether fatty acid alterations represent epiphenomena or risk factors, and (III) similarities and dissociations in fatty acid alterations between different psychiatric disorders. (Historical) epidemiological evidence links fatty acid intake to psychiatric disorder prevalence, corroborated by altered fatty acid concentrations measured in psychiatric patients. These fatty acid alterations are connected with other concomitant pathophysiological mechanisms, including biological stress (hypothalamic-pituitary-adrenal (HPA)-axis and oxidative stress), inflammation, and brain network structure and function. Metabolomics and lipidomics studies are underway to more deeply investigate this complex network of associated neurometabolic alterations. Supplementation of fatty acids as disease-modifying nutraceuticals has clinical potential, particularly add-on eicosapentaenoic acid (EPA) in depressed patients with markers of increased inflammation. However, by interpreting the observed fatty acid alterations as partly (mal)adaptive phenomena, we attempt to nuance translational expectations and provide new clinical applications for these novel neurometabolic insights, e.g., to predict treatment response or depression recurrence. In conclusion, placing fatty acids in context can contribute to further understanding and optimized treatment of psychiatric disorders, in order to diminish their overwhelming burden of disease. PMID: 29524021 [PubMed - as supplied by publisher]

Related Articles In utero and lactational exposure to BDE-47 promotes obesity development in mouse offspring fed a high-fat diet: impaired lipid metabolism and intestinal dysbiosis. Arch Toxicol. 2018 Mar 09;: Authors: Wang D, Yan J, Teng M, Yan S, Zhou Z, Zhu W Abstract In this study, we investigated the effects of in utero and lactational exposure to BDE-47 on the progression of obesity and metabolic dysfunction in a diet-induced obesity model. Pregnant ICR mice were treated via oral gavage with low doses of BDE-47 (0, 0.002, and 0.2 mg/kg body weight) from gestational day 6 to postnatal day 21. After weaning, male offspring were fed an AIN93-based normal diet (ND) or high-fat diet (HFD: 60% calories from fat) for 14 weeks. We examined body weight, liver weight, histopathology, blood biochemistry, gene expression, and serum metabolic changes. A combination of 16S rRNA gene sequencing and 1H NMR-based metabolomics was conducted to examine the effects of BDE-47 on the gut microbiome. Results showed that in utero and lactational exposure to BDE-47 caused a worsening of HFD-induced obesity, hepatic steatosis, and injury; impaired glucose homeostasis and metabolic dysfunction, and mRNA levels of genes involved in lipid metabolism were significantly altered in the BDE-47-treated HFD group. The gut microbiome were perturbed by BDE-47, causing diversity reduction, compositional alteration, and metabolic changes. These changes were more pronounced for BDE-47-treated HFD mice. All these results indicate that early life exposure to low doses of BDE-47 can promote obesity and the development of metabolic dysfunction. PMID: 29523931 [PubMed - as supplied by publisher]

Related Articles Reduced Arogenate Dehydratase Expression: Ramifications for Photosynthesis and Metabolism. Plant Physiol. 2018 Mar 09;: Authors: Höhner R, Marques JV, Ito T, Amakura Y, Budgeon AD, Weitz K, Hixson KK, Davin LB, Kirchhoff H, Lewis NG Abstract Arogenate dehydratase (ADT) catalyzes the final step of phenylalanine (Phe) biosynthesis. Previous work showed that ADT-deficient Arabidopsis thaliana mutants had significantly reduced lignin contents, with stronger reductions in lines that had deficiencies in more ADT isoforms. Here, by analyzing Arabidopsis ADT mutants using our phenomics facility and UPLC-MS based metabolomics, we describe the effects of modulation of ADT on photosynthetic parameters and secondary metabolism. Our data indicate that a reduced carbon flux into Phe biosynthesis in ADT mutants impairs the consumption of photosynthetically produced ATP leading to an increased ATP/ADP ratio, the over-accumulation of transitory starch, and lower electron transport rates. The effect on electron transport rates is caused by an increase in proton motive force across the thylakoid membrane that down-regulates Photosystem II activity by the high energy quenching mechanism. Furthermore, quantitation of secondary metabolites in ADT mutants revealed reduced flavonoid, phenylpropanoid, lignan, and glucosinolate contents, including glucosinolates that are not derived from aromatic amino acids, and significantly increased contents of putative galactolipids and apocarotenoids. Additionally, we used real-time atmospheric monitoring mass spectrometry to compare respiration and carbon fixation rates between wild-type and adt3/4/5/6, our most extreme ADT knock-out mutant, which revealed no significant difference in both night- and day-adapted plants. Overall, these data reveal the profound effects of altered ADT activity and Phe metabolism on secondary metabolites and photosynthesis with implications for plant improvement. PMID: 29523714 [PubMed - as supplied by publisher]

Related Articles Acute loss of iron-sulfur clusters results in metabolic reprogramming and generation of lipid droplets in mammalian cells. J Biol Chem. 2018 Mar 09;: Authors: Crooks DR, Maio N, Lane AN, Jarnik M, Higashi RM, Haller RG, Yang Y, Fan TWM, Linehan M, Rouault TA Abstract Iron-sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant-negative variants of the primary Fe-S biogenesis scaffold protein iron-sulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming associated with loss of Fe-S-containing proteins in several major cellular compartments. Using multiple metabolomics platforms, we observed a ~12-fold increase in intracellular citrate content in Fe-S-deficient cells, a surge that was due to loss of aconitase activity. The excess citrate was generated from glucose-derived acetyl-CoA, and global analysis of cellular lipids revealed that fatty acid biosynthesis increased markedly relative to cellular proliferation rates in Fe-S-deficient cells. We also observed intracellular lipid droplet accumulation in both acutely Fe-S-deficient cells and iron-starved cells. We conclude that deficient Fe-S biogenesis and acute iron deficiency rapidly increase cellular citrate concentrations, leading to fatty acid synthesis and cytosolic lipid droplet formation. Our findings uncover a potential cause of cellular steatosis in non-adipose tissues. PMID: 29523684 [PubMed - as supplied by publisher]

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 2018/03/10PubMed 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 2018/03/10PubMed 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.