PubMed

Metabolomics reveals defensive mechanisms adapted by maize on exposure to high molecular weight polycyclic aromatic hydrocarbons. Chemosphere. 2018 Oct 02;214:771-780 Authors: Sivaram AK, Subashchandrabose SR, Logeshwaran P, Lockington R, Naidu R, Megharaj M Abstract Polycyclic aromatic hydrocarbons are an important group of persistent organic pollutants. Using plants to remediate PAHs has been recognized as a cost-effective and environmentally friendly technique. However, the overall impact of PAHs on the regulation of plant metabolism has not yet been explored. In this study, we analyzed the alteration in the maize (Zea mays L.) metabolome on exposure to high molecular weight PAHs such as benzo[a]pyrene (BaP) and pyrene (PYR) in a hydroponic medium, individually and as a mixture (BaP + PYR) using GC-MS. The differences in the metabolites were analyzed using XCMS (an acronym for various forms (X) of chromatography-mass spectrometry), an online-based data analysis tool. A significant variation in metabolites was observed between treatment groups and the unspiked control group. The univariate, multivariate and pathway impact analysis showed there were more significant alterations in metabolic profiles between individual PAHs and the mixture of BaP and PYR. The marked changes in the metabolites of galactose metabolism and aminoacyl tRNA biosynthesis in PAHs treated maize leaves exhibit the adaptive defensive mechanisms for individual and PAHs mixture. Therefore, the metabolomics approach is essential for an understanding of the complex biochemical responses of plants to PAHs contaminants. This knowledge will shed new light in the field of phytoremediation, bio-monitoring, and environmental risk assessment. PMID: 30296765 [PubMed - as supplied by publisher]

Vitamin D C3-epimer levels are proportionally higher with oral vitamin D supplementation compared to ultraviolet irradiation of skin in mice but not humans. J Steroid Biochem Mol Biol. 2018 Oct 05;: Authors: Ghaly S, Bliuc D, Centre J, Clarke MW, Jones AP, Trend S, Kermode AG, Neale RE, Hart PH Abstract A proportion of circulating 25-hydroxy vitamin D3 (25(OH)D3)) undergoes epimerization to form C3-epi 25(OH)D3 and C3-epi 1,25(OH)2D3. These epimers have less calcaemic activity than non-epimerized metabolites and are not differentiated by many immunoassays when reporting total 25(OH)D3 levels. This study aimed to compare the effect of exposure to ultraviolet radiation (UVR) and oral vitamin D3 supplementation on vitamin D C3-epimer levels. C57Bl/6 female mice were fed either vitamin D-sufficient (vitamin D3 2000 IU/kg) or -deficient diets (no vitamin D3) for 4 weeks. Among the vitamin D-deficient group, the shaved backs of half were irradiated daily for 4 days with 1 kJ/m2 UVR, followed by twice weekly irradiation for 4 weeks. Despite similar 25(OH)D3 levels, the UV-irradiated group had a lower proportion of C3-epi 25(OH)D3 at week 7 (p < 0.05) and week 9 (p < 0.01). C3-epimer concentrations and %C3-epi 25(OH)D3 were also analysed in serum samples from two human clinical trials. These trials investigated the effect of high dose oral vitamin D3 supplementation and narrowband UVB phototherapy, respectively. Serum 25(OH)D3 and the %C3-epi 25(OH)D3 levels measured at 12 months after oral vitamin D3 supplementation were not significantly different to those measured at the time of maximal effect of phototherapy (2 months). Thus, the proportion of 25(OH)D3 that undergoes epimerization is greater with oral vitamin D3 supplementation than exposure to UVR in mice, but not in humans. This important difference between human and murine vitamin D metabolism warrants consideration when interpreting animal studies. PMID: 30296587 [PubMed - as supplied by publisher]

Plasma metabolomic profiling distinguishes right-sided from left-sided colon cancer. Clin Chim Acta. 2018 Oct 05;: Authors: Deng K, Han P, Song W, Wang Z, Zhang F, Xie H, Zhao W, Xu H, Cai Y, Rong Z, Yu X, Cui BB, Li K Abstract BACKGROUND: Many studies have demonstrated that right-sided colon cancer (RCC) has a higher mortality rate and worse prognosis than left-sided colon cancer (LCC). However, the underlying biological mechanism that can account for these differences is unclear. METHODS: In this study, plasma metabolic profiles in 147 LCC patients and 105 RCC patients were systematically analyzed by the ultra high performance liquid chromatography quadruple time-of-flight mass spectrometry (UHPLC-QTOF/MS) platform in conjunction with univariate and multivariate statistical analysis. RESULTS: Metabolic signatures revealed considerable differences between patients with RCC and LCC, and clear separations were observed between the two groups in partial least-squares discriminant analysis score plots. In total, six metabolites were identified as potential metabolite markers for tumor location in RCC compared with LCC, including upregulated trimethylamine N-oxide and indoxyl sulfate, and downregulated anserine, L-targinine, gamma-glutamyl-gamma-aminobutyraldehyde and pyridoxal 5'-phosphate. These differences highlight that significant alternations occur in the pathways of methane metabolism, arginine and proline metabolism, histidine metabolism, beta-alanine metabolism and vitamin B6 metabolism in RCC compared with LCC. CONCLUSIONS: Identified biomarkers and metabolic pathways may facilate our understanding of the different mortality rates and prognoses between RCC and LCC. PMID: 30296444 [PubMed - as supplied by publisher]

Quantification of phenolic acid metabolites in humans by LC-MS: a structural and targeted metabolomics approach. Bioanalysis. 2018 Oct;10(19):1591-1608 Authors: Obrenovich ME, Donskey CJ, Schiefer IT, Bongiovanni R, Li L, Jaskiw GE Abstract AIM: Co-metabolism between a human host and the gastrointestinal microbiota generates many small phenolic molecules such as 3-hydroxy-3-(3-hydroxyphenyl)propanoic acid (3,3-HPHPA), which are reported to be elevated in schizophrenia and autism. Characterization of these chemicals, however, has been limited by analytic challenges. METHODOLOGY/RESULTS: We applied HPLC to separate and quantify over 50 analytes, including multiple structural isomers of 3,3-HPHPA in human cerebrospinal fluid, serum and urine. Confirmation of identity was provided by NMR, by MS and other detection methods. The highly selective methods support rapid quantification of multiple metabolites and exhibit superior chromatographic behavior. CONCLUSION: An improved ultra-HPLC-MS/MS and structural approaches can accurately quantify 3,3-HPHPA and related analytes in human biological matrices. PMID: 30295550 [PubMed - in process]

Incorporating in-source fragment information improves metabolite identification accuracy in untargeted LC-MS datasets. J Proteome Res. 2018 Oct 08;: Authors: Seitzer PM, Searle BC Abstract In-source fragmentation occurs as a byproduct of electrospray ionization. We find that ions produced as a result of in-source fragmentation often match fragment ions produced during MS/MS fragmentation and we take advantage of this phenomenon in a novel algorithm to analyze LC-MS metabolomics datasets. Our approach organizes co-eluting MS1 features into a single peak group and then identifies in-source fragments among co-eluting features using MS/MS spectral libraries. We tested our approach using previously published data of verified metabolites, and compared the results to features detected by other mainstream metabolomics tools. Our results indicate that considering in-source fragment information as a part of the identification process increases annotation quality, allowing us to leverage MS/MS data in spectrum libraries even if MS/MS scans were not collected. PMID: 30295490 [PubMed - as supplied by publisher]

[Metabolomic Profiling of Patients With Cardiovascular Diseases]. Kardiologiia. 2018 Sep;(9):59-62 Authors: Belenkov YN, Privalova EV, Kozhevnikova MV, Korobkova EO, Ilgisonis IS, Kaplunova VY, SHakaryants GA, Appolonova SA, Kuharenko AV, Larcova EV, Mesonzhik NV Abstract Cardiovascular diseases (CVD) are the main cause of death worldwide. A broad study of the pathogenetic mechanisms of the CVD onset and progression has led to understanding of the importance of endothelial dysfunction (ED) in these processes. During recent years intensive work has been conducted in the direction of searching for markers of ED. Metabolomics is an intensively advancing approach to early diagnostics of diseases. Metabolomic analysis based on mass spectrometry allows to study complete metabolic profiles and their deviations resulting from changes in expression of genes and RNA, protein activity, or environmental factors. Metabolomic analysis has already demonstrated significant results in the solving of different scientific and clinical problems. It appears to be a promising method for detecting early biomarkers of CVD. Various aspects of application of metabolomic profiling in the field of cardiovascular diseases are discussed in this article. PMID: 30295200 [PubMed - in process]

Utilization of Analytical Omics Tools in the Molecular Diagnostics of Multiple Myeloma. Curr Mol Med. 2018 Oct 08;: Authors: Kovacs Z, Guttman A Abstract Multiple myeloma (MM) is characterized as the clonal proliferation of malignant plasma B-lymphocytes and even as of today, it is an incurable disease. MM accounts for approximately 10% of all hematologic cancers. Its molecular pathogenesis is poorly understood, but the bone marrow microenvironment of tumor cells and genetic factors have apparent roles in the process. Accurate diagnosis is important to properly identify and stratify the disease, however, MM identification steps are time-consuming and expensive. Thus, development of early molecular diagnostic methods are of high importance in order to start proper therapies as early in the disease progression as possible, given the nature of the poor survival rates/remission periods. Molecular diagnostics via analytical omics represents one of the promising toolsets to speed up the diagnostic process. In this paper, we critically review the utilization of state of the art, high sensitivity analytical omics approaches (genomics, proteomics, metabolomics, lipidomics and glycomics) in MM diagnostics at the molecular level. PMID: 30295190 [PubMed - as supplied by publisher]

Metabolomics of exhaled breath condensate by nuclear magnetic resonance spectroscopy and mass spectrometry: a methodological approach. Curr Med Chem. 2018 Oct 08;: Authors: Maniscalco M, Cutignano A, Paris D, Melck DJ, Molino A, Fuschillo S, Motta A Abstract Respiratory diseases present a very high prevalence in the general population, with an increase in morbidity, mortality and health-care expenses worldwide. They are complex and heterogeneous pathologies that may present different pathological facets in different subjects, often with personal evolution. Therefore, there is a need to identify patients with similar characteristics, prognosis or treatment, defining the so-called phenotype, but also to mark specific differences within each phenotype, defining the endotypes. Biomarkers are very useful to study respiratory phenotypes and endotypes. Metabolomics, one of the recently introduced "omics", is becoming a leading technique for biomarker discovery. For the airways, metabolomics appears to be well suited as the respiratory tract offers a natural matrix, the exhaled breath condensate (EBC), in which several biomarkers can be measured. In this review, we will discuss the main methodological issues related to the application of nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS) to EBC metabolomics for investigating respiratory diseases. PMID: 30295185 [PubMed - as supplied by publisher]

Related Articles The impact of culture conditions on growth and metabolomic profiles of freshwater cyanobacteria. J Appl Phycol. 2018 Feb;30(1):375-384 Authors: Crnkovic CM, May DS, Orjala J Abstract Cultured cyanobacteria produce secondary metabolites with a wide range of biological activities and are an important source of natural products. In the context of secondary metabolite discovery, microbial culture conditions are expected to support optimum growth, induce maximum chemical diversity, and be suitable for the majority of cyanobacterial strains. We investigated the effect of nitrate and phosphate on biomass production and metabolomic profiles of three filamentous freshwater cyanobacterial strains: cf. Oscillatoria sp. UIC 10045, Scytonema sp. UIC 10036, and Nostoc sp. UIC 10110. A standardized inoculation procedure allowed for the assessment of cell mass production. Dried cyanobacterial cell mass was extracted and analyzed by liquid chromatography coupled with high resolution mass spectrometry (UPLC-HRMS), followed by comparative metabolomics analysis using XCMS Online. Results showed that low nitrate media significantly reduced cell mass production for all three strains. Low nitrate also induced production of primary metabolites (heterocyst glycolipids) in strains UIC 10036 and UIC 10110. Changes in phosphate levels affected each strain differently. Strain UIC 10110 showed a significant increase in production of merocyclophane C when cultivated in low phosphate, while strain UIC 10036 displayed higher production of tolytoxin under high phosphate. Additionally, these experiments led to the identification of a potentially new peptide produced by strain UIC 10036. PMID: 30294068 [PubMed]

Related Articles Tumor-Stroma Mechanics Coordinate Amino Acid Availability to Sustain Tumor Growth and Malignancy. Cell Metab. 2018 Sep 28;: Authors: Bertero T, Oldham WM, Grasset EM, Bourget I, Boulter E, Pisano S, Hofman P, Bellvert F, Meneguzzi G, Bulavin DV, Estrach S, Feral CC, Chan SY, Bozec A, Gaggioli C Abstract Dysregulation of extracellular matrix (ECM) deposition and cellular metabolism promotes tumor aggressiveness by sustaining the activity of key growth, invasion, and survival pathways. Yet mechanisms by which biophysical properties of ECM relate to metabolic processes and tumor progression remain undefined. In both cancer cells and carcinoma-associated fibroblasts (CAFs), we found that ECM stiffening mechanoactivates glycolysis and glutamine metabolism and thus coordinates non-essential amino acid flux within the tumor niche. Specifically, we demonstrate a metabolic crosstalk between CAF and cancer cells in which CAF-derived aspartate sustains cancer cell proliferation, while cancer cell-derived glutamate balances the redox state of CAFs to promote ECM remodeling. Collectively, our findings link mechanical stimuli to dysregulated tumor metabolism and thereby highlight a new metabolic network within tumors in which diverse fuel sources are used to promote growth and aggressiveness. Furthermore, this study identifies potential metabolic drug targets for therapeutic development in cancer. PMID: 30293773 [PubMed - as supplied by publisher]

Related Articles Human metabolomics reveal daily variations under nutritional challenges specific to serum and skeletal muscle. Mol Metab. 2018 Oct;16:1-11 Authors: Sato S, Parr EB, Devlin BL, Hawley JA, Sassone-Corsi P Abstract OBJECTIVE: Advances in the field of metabolomics and the concomitant development of bioinformatics tools constitute a promising avenue towards the development of precision medicine and personalized profiling for numerous disease states. Studies in animal models have strengthened this concept, but the application in human subjects is scarce. METHODS: Utilizing high-throughput metabolomics, we have analyzed the metabolome levels of human serum and skeletal muscle in the morning and evening in response to divergent nutritional challenges in order to identify unique signatures present in serum and muscle. RESULTS: We reveal dynamic daily variation of human metabolome unique to serum and muscle. The overall effect of nutritional challenges on the serum and muscle metabolome results in a profound rewiring of morning-evening metabolic profiles in human participants in response to the timing and type of dietary challenge. CONCLUSION: We highlight time-of-day and meal-composition dependence of reprogramming of human metabolome by nutritional challenges. PMID: 30293576 [PubMed - in process]

Related Articles Evaluation of cardiac arrhythmic risks using a rabbit model of left ventricular systolic dysfunction. Eur J Pharmacol. 2018 Aug 05;832:145-155 Authors: Hemmeryckx B, Feng Y, Frederix L, Lox M, Trenson S, Vreeken R, Lu HR, Gallacher D, Ni Y, Lijnen HR Abstract Patients with heart disease have a higher risk to develop cardiac arrhythmias, either spontaneously or drug-induced. In this study, we have used a rabbit model of myocardial infarction (MI) with severe left ventricular systolic dysfunction (LVSD) to study potential drug-induced cardiac risks with N-(piperidin-2-ylmethyl)-2,5-bis(2,2,2-trifluoroethoxy)benzamide (flecainide). Upon ligation of the left circumflex arteries, male New Zealand White rabbits developed a large MI and moderate or severe LVSD 7 weeks after surgery, in comparison to SHAM-operated animals. Subsequently, animals were exposed to escalating doses of flecainide (0.25-4 mg/kg) or solvent. Electrocardiograms (ECG) were recorded before surgery, 1 and 7 weeks after surgery and continuously during the drug protocol. The ECG biomarker iCEB (index of Cardio-Electrophysiological Balance = QT/QRS ratio) was calculated. During the ECG recording at week 1 and week 7 post MI, rabbits had no spontaneous cardiac arrhythmias. When rabbits were exposed to escalating doses of flecainide, 2 out of 5 rabbits with MI and moderate LVSD versus 0 out of 5 solvent-treated rabbits developed arrhythmias, such as ventricular tachycardia/ventricular fibrillation. These were preceded by a marked decrease of iCEB just before the onset (from 4.09 to 2.42 and from 5.56 to 2.25, respectively). Furthermore, 1 out of 5 MI rabbits with moderate LVSD and 1 out of 7 MI rabbits with severe LVSD developed total atrioventricular block after flecainide infusion and died. This rabbit model of MI and severe LVSD may be useful for preclinical evaluation of drug (similar mechanism as flecainide)-induced arrhythmic risks, which might be predicted by iCEB. PMID: 29782862 [PubMed - indexed for MEDLINE]

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 2018/10/08PubMed 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 2018/10/08PubMed 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.

Mutations of Mycobacterium tuberculosis induced by anti-tuberculosis treatment result in metabolism changes and elevation of ethambutol resistance. Infect Genet Evol. 2018 Oct 03;: Authors: Sun L, Zhang L, Wang T, Jiao W, Li Q, Yin Q, Li J, Qi H, Xu F, Shen C, Xiao J, Liu S, Mokrousov I, Huang H, Shen A Abstract Selective pressure from antibiotic use is one of the most important risk factors associated with the development of drug resistance in Mycobacterium tuberculosis (MTB). However, the mechanisms underlying drug resistance at the molecular level remain partly unclear. Therefore, the purpose of this study was to investigate the potential functional effect of novel mutations arising from anti-tuberculosis treatment. We analyzed two multidrug-resistant TB (MDR-TB) isolates from the same patient; one collected before and one almost a year after commencing MDR-TB treatment. The post-treatment isolate exhibited elevated ethambutol resistance. We sequenced the whole genomes of the two clinical isolates and detected six novel polymorphisms affecting the genes Rv1026, nc0021, Rv2155c, Rv2437, and Rv3696c, and the intergenic region between Rv2764c and Rv2765. Metabolomics approach was used to reveal the effect of the found variation on the metabolic pathways of MTB. Partial least squares-discriminant analysis showed a clear differentiation between the two isolates, involving a total of 175 metabolites. Pathway analysis showed that these metabolites are mainly involved in amino sugar and nucleotide sugar metabolism, β-alanine metabolism, sulfur metabolism, and galactose metabolism. The increased ethambutol resistance exhibited by the post-treatment MDR-TB strain could speculatively be linked to the identified genetic variations, which affected the synthesis of a number of metabolites associated with sources of carbon and energy. This may have been the main factor underlying the increased ethambutol resistance of this isolate. PMID: 30292007 [PubMed - as supplied by publisher]

Multi-omics analysis: Repeated exposure of a 3D bronchial tissue culture to whole-cigarette smoke. Toxicol In Vitro. 2018 Oct 03;: Authors: Ishikawa S, Matsumura K, Kitamura N, Takanami Y, Ito S Abstract Cigarette smoke (CS) is a major risk factor in the development of chronic inflammatory lung diseases such as chronic obstructive pulmonary disease. A comprehensive investigation of the biological impacts of chronic CS exposure on lung tissue is therefore important for understanding the pathogenesis of lung disease. We used three-dimensional (3D) organotypic human bronchial tissue cultures and metabolomics, transcriptomics, and proteomics to investigate changes in biological processes affected by repeated whole-CS exposure. We found that CS perturbed central carbon metabolism in relation with oxidative stress responses. Epidermal growth factor receptor, which is involved in the early-stage pathogenesis of airway diseases, was identified as a key regulator of the perturbed processes. Proteomic analysis of proteins in the apical surface liquid of the 3D bronchial tissue cultures indicated that repeated whole-CS exposure induced alterations in the secretion of several known biomarkers of airway diseases, including mucins and matrix metalloproteinases. These findings are consistent with observations from lung disease patients. Overall, our results suggest that 3D bronchial tissue cultures can provide valuable information on tissue-specific alterations in biological processes induced by chronic exposure to CS. PMID: 30291989 [PubMed - as supplied by publisher]

Related Articles Comparative cardio and developmental toxicity induced by the popular medicinal extract of Sutherlandia frutescens (L.) R.Br. detected using a zebrafish Tuebingen embryo model. BMC Complement Altern Med. 2018 Oct 05;18(1):273 Authors: Chen L, Xu M, Gong Z, Zonyane S, Xu S, Makunga NP Abstract BACKGROUND: Sutherlandia frutescens is one of the most promising commercialized, indigenous and medicinal plants of South Africa that is used as an immune-booster, and a traditional treatment for cancer. However, few studies report on its toxicology and dosage in vivo. There is still room to better understand its cytotoxicity effects in animal systems. METHODS: We prepared two extracts, one with 80% (v/v) ethanol, and the other, with water. Both were studied to determine the maximum tolerable concentration when extracts were applied at 0 to 200 μg/ml to a Tuebingen zebrafish embryo line. The development of zebrafish embryos after 24 h post fertilization (hpf) was studied. A concentration range of 5 μg/ml to 50 μg/ml was then chosen to monitor the ontological development of cultured embryos. A liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method was used to study the differences of the two experimental extracts. Chemical variation between the extracts was illustrated using chemometrics. RESULTS: Both extracts led to bleeding and pericardial cyst formation when applied at high concentrations to the zebrafish embryo culture. Chronic teratogenic toxicities, leading to pericardial edema, yolk sac swelling, and other abnormal developmental characteristics, were detected. The aqueous extracts of S. frutescens were less toxic to the larvae than the ethanol extracts, validating preference for aqueous preparations when used in traditional medicine. Chemical differences between the water extracts and alcoholic extracts were analysed using LC-MS/MS. A supervised metabolomics approach, targeting the sutherlandiosides and sutherlandins using orthogonal partial least squares-discriminant analysis (OPLS-DA), illustrated that sutherlandiosides were the main chemical features that can be used to distinguish between the two extracts, despite the extracts being highly similar in their chemical constituents. CONCLUSION: The water extract caused less cytotoxic and abnormal developmental effects compared to the ethanolic extract, and, this is likely due to differences in concentrations of extracted chemicals rather than the chemical profile per se. This study provides more evidence of cytotoxicity effects linked to S. frutescens using the zebrafish embryo bioassay as a study tool. PMID: 30290800 [PubMed - in process]

Related Articles Update on: proteome analysis in thyroid pathology - part II: overview of technical and clinical enhancement of proteomic investigation of the thyroid lesions. Expert Rev Proteomics. 2018 Oct 05;: Authors: Piga I, Casano S, Smith A, Tettamanti S, Leni D, Capitoli G, Pincelli AI, Scardilli M, Galimberti S, Magni F, Pagni F Abstract INTRODUCTION: An accurate diagnostic classification of thyroid lesions remains an important clinical aspect that needs to be addressed in order to avoid "diagnostic" thyroidectomies. Among the several "omics" techniques, proteomics is playing a pivotal role in the search for diagnostic markers. In recent years, different approaches have been used, taking advantage of the technical improvements related to mass spectrometry that have occurred. Areas covered: The review provides an update of the recent findings in diagnostic classification, in genetic definition and in the investigation of thyroid lesions based on different proteomics approaches and on different type of specimens: cytological, surgical and biofluid samples. A brief section will discuss how these findings can be integrated with those obtained by metabolomics investigations. Expert commentary: Among the several proteomics approaches able to deepen our knowledge of the molecular alterations of the different thyroid lesions, MALDI-MSI is strongly emerging above all. In fact, MS-imaging has also been demonstrated to be capable of distinguishing thyroid lesions, based on their different molecular signatures, using cytological specimens. The possibility to use the material obtained by the fine needle aspiration makes MALDI-MSI a highly promising technology that could be implemented into the clinical and pathological units. PMID: 30290700 [PubMed - as supplied by publisher]

Related Articles Normal pregnancy induced glucose metabolic stress in a longitudinal cohort of healthy women: Novel insights generated from a urine metabolomics study. Medicine (Baltimore). 2018 Oct;97(40):e12417 Authors: Wang M, Xia W, Li H, Liu F, Li Y, Sun X, Lu S, Xu S Abstract During normal pregnancy, mothers face a unique physiological challenge in the adaptation of glucose metabolism in preparation for the metabolic stress presented by fetal development. However, the responsible mechanism remains elusive. The purpose of this study is to investigate the mechanism of the metabolic stress of glucose metabolism in pregnant women using metabolomics method.A Ultra Performance Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometer-based untargeted metabolomics study was performed to investigate the dynamic urinary signature of the intermediates of glucose metabolism in a longitudinal cohort of 232 healthy pregnant women in their first, second, and third trimesters.Twelve glucose metabolic intermediates were screened out from hundreds of candidate metabolites using partial least squares discriminant analysis models. These 12 markers were mainly involved in the metabolic pathways of insulin resistance, glycolysis/gluconeogenesis, tricarboxylic acid cycle, nonabsorbable carbohydrate metabolism, and N-glycan biosynthesis. In particular, L-acetylcarnitine, a metabolite that is beneficial for the amelioration of insulin resistance, decreased in a time-dependent manner during normal pregnancy. Moreover, thiamine pyrophosphate, an intermediate product of glycolysis/gluconeogenesis, significantly increased in the second trimester, and argininosuccinic acid and oxalosuccinic acid, intermediates involved in the tricarboxylic acid cycle, significantly decreased in the third trimester, suggesting an increased glucose demand in the maternal body during fetal development.These findings provide novel insight into the normal pregnancy-induced elevation of insulin resistance and glycolysis/gluconeogenesis, as well as the observed reduction in the aerobic oxidation of glucose. PMID: 30290597 [PubMed - in process]

Methionine supplementation stimulates mitochondrial respiration. Biochim Biophys Acta Mol Cell Res. 2018 Oct 02;: Authors: Tripodi F, Castoldi A, Nicastro R, Reghellin V, Lombardi L, Airoldi C, Falletta E, Maffioli E, Scarcia P, Palmieri L, Alberghina L, Agrimi G, Tedeschi G, Coccetti P Abstract Mitochondria play essential metabolic functions in eukaryotes. Although their major role is the generation of energy in the form of ATP, they are also involved in maintenance of cellular redox state, conversion and biosynthesis of metabolites and signal transduction. Most mitochondrial functions are conserved in eukaryotic systems and mitochondrial dysfunctions trigger several human diseases. By using multi-omics approach, we investigate the effect of methionine supplementation on yeast cellular metabolism, considering its role in the regulation of key cellular processes. Methionine supplementation induces an up-regulation of proteins related to mitochondrial functions such as TCA cycle, electron transport chain and respiration, combined with an enhancement of mitochondrial pyruvate uptake and TCA cycle activity. This metabolic signature is more noticeable in cells lacking Snf1/AMPK, the conserved signalling regulator of energy homeostasis. Remarkably, snf1Δ cells strongly depend on mitochondrial respiration and suppression of pyruvate transport is detrimental for these cells in methionine condition, indicating that respiration mostly relies on pyruvate flux into mitochondrial pathways. These data provide new insights into the regulation of mitochondrial metabolism and extends our understanding on the role of methionine in regulating energy signalling pathways. PMID: 30290237 [PubMed - as supplied by publisher]