PubMed

Related Articles Metabolite quantification of faecal extracts from colorectal cancer patients and healthy controls. Oncotarget. 2018 Sep 07;9(70):33278-33289 Authors: Le Gall G, Guttula K, Kellingray L, Tett AJ, Ten Hoopen R, Kemsley KE, Savva GM, Ibrahim A, Narbad A Abstract Colorectal cancer (CRC), a primary cause of morbidity and mortality worldwide is expected to rise in the coming years. A better understanding of the metabolic changes taking place during the disease progression is needed for effective improvements of screening strategies and treatments. In the present study, Nuclear Magnetic Resonance (NMR) metabolomics was used to quantify the absolute concentrations of metabolites in faecal extracts from two cohorts of CRC patients and healthy controls. The quantification of over 80 compounds revealed that patients with CRC had increased faecal concentrations of branched chain fatty acids (BCFA), isovalerate and isobutyrate plus valerate and phenylacetate but diminished concentrations of amino acids, sugars, methanol and bile acids (deoxycholate, lithodeoxycholate and cholate). These results suggest that alterations in microbial activity and composition could have triggered an increase in utilisation of host intestinal slough cells and mucins and led to an increase in BCFA, valerate and phenylacetate. Concurrently, a general reduction in the microbial metabolic function may have led to reduced levels of other components (amino acids, sugars and bile acids) normally produced under healthy conditions. This study provides a thorough listing of the most abundant compounds found in human faecal waters and presents a template for absolute quantification of metabolites. The production of BCFA and phenylacetate in colonic carcinogenesis warrants further investigations. PMID: 30279959 [PubMed]

Related Articles A Non-Targeted LC-MS Profiling Reveals Elevated Levels of Carnitine Precursors and Trimethylated Compounds in the Cord Plasma of Pre-Eclamptic Infants. Sci Rep. 2018 Oct 02;8(1):14616 Authors: Jääskeläinen T, Kärkkäinen O, Jokkala J, Litonius K, Heinonen S, Auriola S, Lehtonen M, Hanhineva K, Laivuori H, FINNPEC Abstract Preeclampsia (PE) is a complex pregnancy disorder. It is not extensively known how the metabolic alterations of PE women contribute to the metabolism of newborn. We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of plasma from umbilical cord differs between infants born to PE and non-PE pregnancies in the FINNPEC study. Cord plasma was available from 42 newborns born from PE and 53 from non-PE pregnancies. 133 molecular features differed between PE and non-PE newborns after correction for multiple testing. Decreased levels of 4-pyridoxic acid were observed in the cord plasma samples of PE newborns when compared to non-PE newborns. Compounds representing following areas of metabolism were increased in the cord plasma of PE newborns: urea and creatine metabolism; carnitine biosynthesis and acylcarnitines; putrescine metabolites; tryptophan metabolism and phosphatidylcholines. To our knowledge, this study is the first one to apply LC-MS based metabolomics in cord plasma of PE newborns. We demonstrate that this strategy provides a global picture of the widespread metabolic alterations associated with PE and particularly the elevated levels of carnitine precursors and trimethylated compounds appear to be associated with PE at birth. PMID: 30279541 [PubMed - in process]

Related Articles Pyrophosphate inhibits gluconeogenesis by restricting UDP-glucose formation in vivo. Sci Rep. 2018 Oct 02;8(1):14696 Authors: Ferjani A, Kawade K, Asaoka M, Oikawa A, Okada T, Mochizuki A, Maeshima M, Hirai MY, Saito K, Tsukaya H Abstract Pyrophosphate (PPi) is produced by anabolic reactions and serves as an energy donor in the cytosol of plant cells; however, its accumulation to toxic levels disrupts several common biosynthetic pathways and is lethal. Before acquiring photosynthetic capacity, young seedlings must endure a short but critical heterotrophic period, during which they are nourished solely by sugar produced from seed reserves by the anabolic process of gluconeogenesis. Previously, we reported that excess PPi in H+-PPase-knockout fugu5 mutants of Arabidopsis thaliana severely compromised gluconeogenesis. However, the precise metabolic target of PPi inhibition in vivo remained elusive. Here, CE-TOF MS analyses of major metabolites characteristic of gluconeogenesis from seed lipids showed that the Glc6P;Fru6P level significantly increased and that Glc1P level was consistently somewhat higher in fugu5 compared to wild type. In contrast, the UDP-Glc level decreased significantly in the mutants. Importantly, specific removal of PPi in fugu5, and thus in AVP1pro:IPP1 transgenic lines, restored the Glc1P and the Glc6P;Fru6P levels, increased the UDP-Glc level ~2.0-fold, and subsequently increased sucrose synthesis. Given the reversible nature of the Glc1P/UDP-Glc reaction, our results indicate that UGP-Glc pyrophosphorylase is the major target when excess PPi exerts inhibitory effects in vivo. To validate our findings, we analyzed metabolite responses using a mathematical theory called structural sensitivity analysis (SSA), in which the responses of concentrations in reaction systems to perturbations in enzyme activity are determined from the structure of the network alone. A comparison of our experimental data with the results of pure structural theory predicted the existence of unknown reactions as the necessary condition for the above metabolic profiles, and confirmed the above results. Our data support the notion that H+-PPase plays a pivotal role in cytosolic PPi homeostasis in plant cells. We propose that the combination of metabolomics and SSA is powerful when seeking to identify and predict metabolic targets in living cells. PMID: 30279540 [PubMed - in process]

Related Articles Diagnostic value of plasma tryptophan and symmetric dimethylarginine levels for acute kidney injury among tacrolimus-treated kidney transplant patients by targeted metabolomics analysis. Sci Rep. 2018 Oct 02;8(1):14688 Authors: Zhang F, Wang Q, Xia T, Fu S, Tao X, Wen Y, Chan S, Gao S, Xiong X, Chen W Abstract Few literatures have evaluated the exact role of metabolomics in the identification process of potential biomarkers for acute kidney injury among the patients receiving renal transplantation. On top of this, the success of metabolomics in biomarker translation seems to lie in the robust quantitative method. As such, a single-center retrospective observational study was conducted enrolling 42 patients underwent renal transplantation with/without acute kidney injury, as well as 24 healthy volunteers, in Shanghai Changzheng Hospital. Plasma amino acid metabolic patterns for the participants were investigated by targeted UHPLC-MS/MS metabolic profiling. The most significant changes of the explored metabolites were related to the disturbance of tryptophan metabolism and arginine metabolism. Abnormal circulating tryptophan and symmetric dimethylarginine were identified to be potential biomarkers of acute kidney injury, combination of which showed a higher area under receiver-operator curve value (AUC = 0.901), improved sensitivity (0.889) and specificity (0.831) compared with creatinine only. Overall, these results revealed that targeted metabolomics analysis would be a potent and promising strategy for identification and pre-validation of biomarkers of acute kidney injury in renal transplantation patients. PMID: 30279519 [PubMed - in process]

Related Articles Renoprotective effect of Zhenwu decoction against renal fibrosis by regulation of oxidative damage and energy metabolism disorder. Sci Rep. 2018 Oct 02;8(1):14627 Authors: Li S, Xiao X, Han L, Wang Y, Luo G Abstract Zhenwu decoction (ZWD) is a promising traditional Chinese prescription against renal fibrosis, while its underlying mechanism remains unclear. Rat model of renal fibrosis were established and divided into control group, model group, ZWD treatment group and enalapril maleate treatment group. Metabolic profiles on serum samples from each group were acquired by using ultra performance liquid chromatography coupled with quadrupole time-of-flight high-resolution mass spectrometry. Metabolomics combined with molecular biology were comparatively conducted on samples of various groups. Fifteen potential biomarkers were identified and these biomarkers are mainly phospholipids and fatty acids. The results showed renal fibrosis was associated with oxidative damage and energy metabolism disorder. The results of histopathology, biochemistry and metabolomics demonstrated that ZWD exhibited an efficient renoprotective effect by alleviating oxidative stress, increasing energy metabolism and regulating fibrotic cytokines. This study provided scientific support for the research and development of new drugs from traditional Chinese medicine. PMID: 30279506 [PubMed - in process]

Related Articles Metabolic Alterations Associated with Atorvastatin/Fenofibric Acid Combination in Patients with Atherogenic Dyslipidaemia: A Randomized Trial for Comparison with Escalated-Dose Atorvastatin. Sci Rep. 2018 Oct 02;8(1):14642 Authors: Han JS, Kim K, Jung Y, Lee JH, Namgung J, Lee HY, Suh J, Hwang GS, Lee SH Abstract In the current study, the metabolic effects of atorvastatin dose escalation versus atorvastatin/fenofibric acid combination were compared using metabolomics analyses. Men and women with combined hyperlipidaemia were initially prescribed atorvastatin (10 mg, ≥4 weeks). Patients who reached low-density lipoprotein-cholesterol targets, but had triglyceride and high-density lipoprotein-cholesterol levels ≥150 mg/dL and <50 mg/dL, respectively, were randomized to receive atorvastatin 20 mg or atorvastatin 10 mg/fenofibric acid 135 mg for 12 weeks. Metabolite profiling of serum was performed and changes in metabolites after drug treatment in the two groups were compared. Analysis was performed using patients' samples obtained before and after treatment. Of 89 screened patients, 37 who met the inclusion criteria were randomized, and 34 completed the study. Unlike that in the dose-escalation group, distinct clustering of both lipid and aqueous metabolites was observed in the combination group after treatment. Most lipid metabolites of acylglycerols and many of ceramides decreased, while many of sphingomyelins increased in the combination group. Atorvastatin dose escalation modestly decreased lysophosphatidylcholines; however, the effect of combination therapy was variable. Most aqueous metabolites decreased, while L-carnitine remarkably increased in the combination group. In conclusion, the atorvastatin/fenofibric acid combination induced distinct metabolite clustering. Our results provide comprehensive information regarding metabolic changes beyond conventional lipid profiles for this combination therapy. PMID: 30279504 [PubMed - in process]

Related Articles Remodeling of the collagen matrix in aging skin promotes melanoma metastasis and affects immune cell motility. Cancer Discov. 2018 Oct 02;: Authors: Kaur A, Ecker BL, Douglass SM, Kugel CH, Webster MR, Almeida FV, Somasundaram R, Hayden J, Ban E, Ahmadzadeh H, Franco-Barraza J, Shah N, Mellis IA, Keeney F, Kossenkov A, Tang HY, Yin X, Liu Q, Xu X, Fane M, Brafford P, Herlyn M, Speicher DW, Wargo JA, Tetzlaff MT, Haydu LE, Raj A, Shenoy V, Cukierman E, Weeraratna AT Abstract Physical changes in skin are among the most visible signs of aging. We found that young dermal fibroblasts secrete high levels of extracellular matrix (ECM) constituents, including proteoglycans, glycoproteins and cartilage-linking proteins. The most abundantly secreted was HAPLN1, a hyaluronic and proteoglycan link protein. HAPLN1 was lost in aged fibroblasts, resulting in a more aligned ECM that promoted metastasis of melanoma cells. Reconstituting HAPLN1 inhibited metastasis in an aged microenvironment, in 3D skin reconstruction models, and in vivo. Intriguingly, aged fibroblast-derived matrices had the opposite effects on the migration of T-cells, inhibiting their motility. HAPLN1 treatment of aged fibroblasts restored motility of mononuclear immune cells, while impeding that of polymorphonuclear immune cells, which in turn affected Treg recruitment. These data suggest while age-related physical changes in the ECM can promote tumor cell motility, they may adversely impact the motility of some immune cells, resulting in an overall change in the immune microenvironment. Understanding the physical changes in aging skin may provide avenues for more effective therapy for older melanoma patients. PMID: 30279173 [PubMed - as supplied by publisher]

Related Articles Red blood cells as an organ? How deep omics characterization of the most abundant cell in the human body highlights other systemic metabolic functions beyond oxygen transport. Expert Rev Proteomics. 2018 Oct 02;: Authors: Nemkov T, Reisz JA, Xia Y, Zimring JC, D'Alessandro A Abstract INTRODUCTION: Recently, the classification of two "novel" organs, the mesentere and interstitium, was saluted as a scientific breakthrough and disseminated into mainstream media. The novelty of these findings did not pertain to the characterization of some previously unexplored phenomena, rather to the appreciation that well-established tissues may play some hitherto unexplored functions critical to system homeostasis. Areas covered: Here we provocatively comment on the potential classification of red blood cells - by far the most abundant host cell in the human body (~83% of the total cells) - as an organ involved in many functions beyond gas transport. In this perspective article, we describe some of these functions with a special emphasis on the role erythrocytes play with respect to systemic metabolic homeostasis. We thus focus on how these functions modulate the cross-talk of red blood cells among each other and with other cell types including immune cells. Expert commentary: The appreciation of RBCs as an organ impacting systemic metabolic homeostasis and other cell functions while engaging in complex metabolic activity beyond oxygen transport can foster the development of novel therapeutic interventions in pathologic hypoxemia, inflammation, neurodgenerative diseases, aging and cancer. PMID: 30278801 [PubMed - as supplied by publisher]

Related Articles Use of 5-azacytidine in a proof-of-concept study to evaluate the impact of pre-natal and post-natal exposures, as well as within generation persistent DNA methylation changes in Daphnia. Ecotoxicology. 2018 Jul;27(5):556-568 Authors: Athanasio CG, Sommer U, Viant MR, Chipman JK, Mirbahai L Abstract Short-term exposures at critical stages of development can lead to delayed adverse effects long after the initial stressor has been removed, a concept referred to as developmental origin of adult disease. This indicates that organisms' phenotypes may epigenetically reflect their past exposure history as well as reflecting chemicals currently present in their environment. This concept has significant implications for environmental monitoring. However, there is as yet little or no implementation of epigenetics in environmental risk assessment. In a proof-of-principle study we exposed Daphnia magna to 5-azacytidine, a known DNA de-methylating agent. Exposures covered combinations of prenatal and postnatal exposures as well as different exposure durations and recovery stages. Growth, the transcription of genes and levels of metabolites involved in regulating DNA methylation, and methylation levels of several genes were measured. Our data shows that prenatal exposures caused significant changes in the methylome of target genes, indicating that prenatal stages of Daphnia are also susceptible to same level of change as post-natal stages of Daphnia. While the combination of pre- and postnatal exposures caused the most extreme reduction in DNA methylation compared to the control group. Furthermore, some of the changes in the methylation patterns were persistent even after the initial stressor was removed. Our results suggest that epigenetic biomarkers have the potential to be used as indicators of past chemical exposure history of organisms and provide strong support for implementing changes to the current regimes for chemical risk assessment to mimic realistic environmental scenarios. PMID: 29623456 [PubMed - indexed for MEDLINE]

49 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 2018/10/03PubMed 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.

49 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 2018/10/03PubMed 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.

29 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 2018/10/02PubMed 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.

Assessment of penconazole exposure in winegrowers using urinary biomarkers. Environ Res. 2018 Sep 13;168:54-61 Authors: Mercadante R, Polledri E, Rubino FM, Mandic-Rajcevic S, Vaiani A, Colosio C, Moretto A, Fustinoni S Abstract Penconazole (PEN) is a fungicide used in agriculture. The aim of this work was to evaluate the exposure to PEN in vineyard workers focusing on urinary biomarkers. Twenty-two agricultural workers were involved in the study; they were investigated during PEN applications and re-entry work, performed for 1-4 consecutive working days, for a total of 42 mixing and applications and 12 re-entries. Potential and actual dermal exposure, including hand exposure, were measured using pads and hand washes. Urine samples were collected starting before the first application, continuing during the work shift, and ending 48 h after the last shift. The determination of PEN in dermal samples and PEN metabolites in urine was performed by liquid chromatography tandem mass spectrometry. Dermal potential body exposure and actual total exposure showed median levels ranging from 18 to 3356µg and from 21 to 111 µg, respectively. Urinary monohydroxyl-derivative PEN-OH was the most abundant metabolite; its excretion rate peaked within 24 h after the work shift. In this period, median concentrations of PEN-OH and the carboxyl-derivative PEN-COOH ranged from 15.6 to 27.6 µg/L and from 2.5 to 10.2 µg/L, respectively. The concentration of PEN-OH during the work shift, in the 24 h after and in the 25-48 h after the work shift were correlated with actual body and total dermal exposure (Pearson's r from 0.279 to 0.562). Our results suggest that PEN-OH in the 24 h post-exposure urine is a promising candidate for biomonitoring PEN exposure in agricultural workers. PMID: 30268961 [PubMed - as supplied by publisher]

Antidepressant-like effect of salidroside and curcumin on the immunoreactivity of rats subjected to a chronic mild stress model. Food Chem Toxicol. 2018 Sep 27;: Authors: Vasileva LV, Saracheva KE, Ivanovska MV, Petrova AP, Marchev AS, Georgiev MI, Murdjeva MA, Getova DP Abstract Deregulated cytokines' production is found in depressed patients. Salidroside and curcumin both have been described with potential antidepressant-like activities. The present study investigated the effect of pure salidroside, curcumin and their combination on the immunoreactivity of animals, subjected to a chronic mild stress (CMS) model, followed by lipopolysaccharide (LPS)-induced inflammation. Wistar male rats were separated in the following six groups: control, CMS model, fluoxetine (2.5 mg/kg, oral), salidroside (5 mg/kg, oral), curcumin (20 mg/kg, oral) and salidroside + curcumin (5 mg/kg + 20 mg/kg, oral). Changes in glucose preference, spatial learning and exploratory behavior were recorded. The IL-6 levels in the rats' sera and of the TNF-α levels in the rats' sera and the brain tissue homogenate were evaluated. The groups exposed to stress and treated with fluoxetine, salidroside, curcumin or salidroside + curcumin showed increase in the glucose preference and locomotor activity, as well as, decrease in the escape latency and the cytokines' levels compared to the CMS model group. The chronic stress induced behavioral alternations and increased cytokines' levels in rats which were reversed by administration of salidroside and curcumin, suggesting antidepressant-like effects comparable to that of fluoxetine and potential synergistic interaction regarding the anti-inflammatory and anti-stress effects. PMID: 30268794 [PubMed - as supplied by publisher]

Hepatoprotection of Herpetospermum caudigerum Wall. against CCl4-induced liver fibrosis on rats. J Ethnopharmacol. 2018 Sep 27;: Authors: Li MH, Feng X, Deng Ba DJ, Chen C, Ruan LY, Xing YX, Chen LY, Zhong GJ, Wang JS Abstract ETHNOPHARMACOLOGICAL RELEVANCE: Herpetospermum caudigerum Wall. (HCW) is a traditional Tibetan medicine, which has been used to ameliorate liver injuries in the folk. AIM OF THE STUDY: Liver fibrosis has been recognized as a major lesion of the liver that leads to liver cirrhosis/hepatocarcinoma and even to death in the end. This study aims to demonstrate the protective effect of HCW against CCl4-induced liver injury in rats and to explore the underlying mechanisms. MATERIALS AND METHODS: Hepatic fibrosis was induced by intraperitoneal injection of CCl4. Liver function markers, fibrosis markers, serum anti-oxidation enzymes as well as elements levels were determined. Serum and liver tissues were subjected to NMR-based metabolomics and multivariate statistical analysis. RESULTS: HCW could significantly reduce the elevated levels of fibrosis markers such as hyaluronidase, laminin, Type III procollagen and Type IV collagen in the serum, improve the activities of the antioxidant enzymes, and effectively reverse the abnormal levels of elements in liver fibrosis rats. Correlation network analysis revealed that HCW could treat liver fibrosis by ameliorating oxidative stress, repairing the impaired energy metabolisms and reversing the disturbed amino acids and nucleic acids metabolisms. CONCLUSION: This integrated metabolomics approach confirmed the validity of the traditional use of HCW in the treatment of liber fibrosis, providing new insights into the underlying mechanisms. PMID: 30268654 [PubMed - as supplied by publisher]

Related Articles Lipid profile perturbations in the plasma and lungs of mice with LPS-induced acute lung injury revealed by UHPLC-ESI-Q Exactive HF MS analysis. J Pharm Biomed Anal. 2018 Sep 19;162:242-248 Authors: Shan J, Qian W, Kang A, Peng L, Xie T, Lin L, Di L, Xiao P, Zhou W Abstract An UHPLC-ESI-Q Exactive HF MS-based lipidomics method was successfully applied to profile various lipids from the plasma and lungs of mice intranasally challenged with lipopolysaccaride (LPS). Response trends of lipids to LPS were graphically represented by variable importance in projection (VIP) plot, heat map, and bar plot. As a result, 77 differential lipids in the lung and 13 differential lipids in the plasma were identified by comparison between healthy and LPS- induced mice. These results revealed the correlation between inflammation and lipids metabolism. The differentially regulated lipids could also be potentially used as biomarkers for inflammation. PMID: 30268025 [PubMed - as supplied by publisher]

Related Articles Fasting serum α‑hydroxybutyrate and pyroglutamic acid as important metabolites for detecting isolated post-challenge diabetes based on organic acid profiles. J Chromatogr B Analyt Technol Biomed Life Sci. 2018 Sep 04;1100-1101:6-16 Authors: Chou J, Liu R, Yu J, Liu X, Zhao X, Li Y, Liu L, Sun C Abstract The aim of this study was to develop a method to detect serum organic acid profiles in patients with isolated post-challenge diabetes (IPD) and to compare the metabolites between IPD patients, type 2 diabetes mellitus (T2DM) and healthy controls. We developed a gas chromatography-mass spectrometry method to detect serum organic acids and validated it using serum from 40 patients with IPD, 47 with newly diagnosed T2DM, and 48 healthy controls. We then analyzed the organic acid profiles by multivariate analysis to identify potential metabolites. This method allowed the fast and accurate measurement of 27 organic acids in serum. Serum organic acid profiles differed significantly among IPD patients, T2DM patients, and healthy controls. IPD samples had significantly higher concentrations of α‑hydroxybutyrate and β‑hydroxybutyrate (P < 0.05) and lower pyroglutamic acid concentration (P < 0.05) compared with the healthy controls, and the area under the curve for the combination of α‑hydroxybutyrate and pyroglutamic acid was 0.863 for the IPD group. These results provide useful information regarding the changes in organic acid metabolism associated with IPD. Measurement of these metabolites in fasting serum from IPD patients may provide useful diagnostic and/or prognostic biomarkers, as well as helpful markers for the therapeutic monitoring of IPD patients. PMID: 30267980 [PubMed - as supplied by publisher]

Related Articles Trans-omic Analysis Reveals Selective Responses to Induced and Basal Insulin across Signaling, Transcriptional, and Metabolic Networks. iScience. 2018 Sep 28;7:212-229 Authors: Kawata K, Hatano A, Yugi K, Kubota H, Sano T, Fujii M, Tomizawa Y, Kokaji T, Tanaka KY, Uda S, Suzuki Y, Matsumoto M, Nakayama KI, Saitoh K, Kato K, Ueno A, Ohishi M, Hirayama A, Soga T, Kuroda S Abstract The concentrations of insulin selectively regulate multiple cellular functions. To understand how insulin concentrations are interpreted by cells, we constructed a trans-omic network of insulin action in FAO hepatoma cells using transcriptomic data, western blotting analysis of signaling proteins, and metabolomic data. By integrating sensitivity into the trans-omic network, we identified the selective trans-omic networks stimulated by high and low doses of insulin, denoted as induced and basal insulin signals, respectively. The induced insulin signal was selectively transmitted through the pathway involving Erk to an increase in the expression of immediate-early and upregulated genes, whereas the basal insulin signal was selectively transmitted through a pathway involving Akt and an increase of Foxo phosphorylation and a reduction of downregulated gene expression. We validated the selective trans-omic network in vivo by analysis of the insulin-clamped rat liver. This integrated analysis enabled molecular insight into how liver cells interpret physiological insulin signals to regulate cellular functions. PMID: 30267682 [PubMed]

Related Articles Fermentation performance and metabolomic analysis of an engineered high-yield PUFA-producing strain of Schizochytrium sp. Bioprocess Biosyst Eng. 2018 Sep 28;: Authors: Geng L, Chen S, Sun X, Hu X, Ji X, Huang H, Ren L Abstract The ω-3/long-chain polyunsaturated fatty acids (LC-PUFAs) play an important role in human health, but they cannot be synthesized in sufficient amounts by the human body. In a previous study, we obtained an engineered Schizochytrium sp. strain (HX-RS) by exchanging the acyltransferase (AT) gene, and it was able to co-produce docosahexaenoic acid and eicosapentaenoic acid. To investigate the mechanism underlying the increase of PUFA content in HX-RS, the discrepancies of fermentation performance, key enzyme activities and intracellular metabolites between HX-RS and its wild-type parent strain (WTS) were analyzed via fed-batch fermentation in 5-L bioreactors. The results showed that the cell dry weight (CDW) of HX-RS was higher than that of the WTS. Metabolomics combined with multivariate analysis showed that 4-aminobutyric acid, proline and glutamine are potential biomarkers associated with cell growth and lipid accumulation of HX-RS. Additionally, the shift of metabolic flux including a decrease of glyceraldehyde-3-phosphate content, high flux from pyruvate to acetyl-CoA, and a highly active glycolysis pathway were also found to be closely related to the high PUFA yield of the engineered strain. These findings provide new insights into the effects of exogenous AT gene expression on cell proliferation and fatty acid metabolism. PMID: 30267145 [PubMed - as supplied by publisher]

Related Articles Use of Plasma Metabolomics to Analyze Phenotype-Genotype Relationships in Young Hypercholesterolemic Females. J Lipid Res. 2018 Sep 28;: Authors: Zhang X, Rimbert A, Balder W, Zwinderman AH, Kuivenhoven JA, Dallinga-Thie GM, Groen AK Abstract Hypercholesterolemia is characterized by high plasma low density lipoprotein (LDL) cholesterol and often caused by genetic mutations in LDLR, APOB or PCSK9. However, a substantial proportion of hypercholesterolemic subjects do not have any mutations in these canonical genes, leaving the underlying pathobiology to be determined. In this study, we investigated whether combining plasma metabolomics with genetic information increases insight in the biology of hypercholesterolemia. For this proof of concept study, we combined plasma metabolites from 119 hypercholesterolemic females with genetic information on the LDL canonical genes. Using hierarchical clustering we identified four subtypes of hypercholesterolemia, which could be distinguished along two axes represented by triglyceride and large LDL particle concentration. Subjects with mutations in LDLR or APOB preferentially clustered together suggesting that patients with defects in the LDL receptor pathway show a distinctive metabolomics profile. In conclusion, we show the potential of using metabolomics to segregate hypercholesterolemic subjects in different clusters, which may help in targeting genetic analysis. PMID: 30266833 [PubMed - as supplied by publisher]