PubMed

Related Articles Gut microbiome-related metabolic changes in plasma of antibiotic-treated rats. Arch Toxicol. 2017 Mar 23;: Authors: Behr C, Kamp H, Fabian E, Krennrich G, Mellert W, Peter E, Strauss V, Walk T, Rietjens IM, van Ravenzwaay B Abstract The intestinal microbiota contributes to the metabolism of its host. Adequate identification of the microbiota's impact on the host plasma metabolites is lacking. As antibiotics have a profound effect on the microbial composition and hence on the mammalian-microbiota co-metabolism, we studied the effects of antibiotics on the "functionality of the microbiome"-defined as the production of metabolites absorbed by the host. This metabolomics study presents insights into the mammalian-microbiome co-metabolism of endogenous metabolites. To identify plasma metabolites related to microbiome changes due to antibiotic treatment, we have applied broad-spectrum antibiotics belonging to the class of aminoglycosides (neomycin, gentamicin), fluoroquinolones (moxifloxacin, levofloxacin) and tetracyclines (doxycycline, tetracycline). These were administered orally for 28 days to male rats including blood sampling for metabolic profiling after 7, 14 and 28 days. Fluoroquinolones and tetracyclines can be absorbed from the gut; whereas, aminoglycosides are poorly absorbed. Hippuric acid, indole-3-acetic acid and glycerol were identified as key metabolites affected by antibiotic treatment, beside changes mainly concerning amino acids and carbohydrates. Inter alia, effects on indole-3-propionic acid were found to be unique for aminoglycosides, and on 3-indoxylsulfate for tetracyclines. For each class of antibiotics, specific metabolome patterns could be established in the MetaMap®Tox data base, which contains metabolome data for more than 550 reference compounds. The results suggest that plasma-based metabolic profiling (metabolomics) could be a suitable tool to investigate the effect of antibiotics on the functionality of the microbiome and to obtain insight into the mammalian-microbiome co-metabolism. PMID: 28337503 [PubMed - as supplied by publisher]

Related Articles Changes in intestinal microbiota composition and metabolism coincide with increased intestinal permeability in young adults under prolonged physiologic stress. Am J Physiol Gastrointest Liver Physiol. 2017 Mar 23;:ajpgi.00066.2017 Authors: Karl JP, Margolis LM, Madslien EH, Murphy NE, Castellani JW, Gundersen Y, Hoke AV, Levangie MW, Kumar R, Chakraborty N, Gautam A, Hammamieh R, Martini S, Montain SJ, Pasiakos SM Abstract The magnitude, temporal dynamics, and physiologic effects of intestinal microbiome responses to physiologic stress are poorly characterized. This study used a systems biology approach and multiple-stressor military training environment to determine the effects of physiologic stress on intestinal microbiota composition and metabolic activity, and intestinal permeability (IP). 73 Soldiers were provided three rations/d with or without protein- or carbohydrate-based supplements during a four day cross-country ski march (STRESS). IP was measured before and during STRESS. Blood and stool samples were collected before and after STRESS to measure inflammation, stool microbiota, and stool and plasma global metabolite profiles. IP increased 62%±57% (mean±SD, P<0.001) during STRESS independent of diet group, and was associated with increased inflammation. Intestinal microbiota responses were characterized by increased α-diversity, and changes in the relative abundance of >50% of identified genera, including increased abundances of less dominant taxa at the expense of more dominant taxa such as Bacteroides. Changes in intestinal microbiota composition were linked to 23% of metabolites that were significantly altered in stool after STRESS. Pre-STRESS Actinobacteria relative abundance, and changes in serum IL-6 and stool cysteine concentrations, collectively, accounted for 84% of the variability in the change in IP. Findings demonstrate that a multiple-stressor military training environment induced increases in IP that were associated with alterations in markers of inflammation, and with intestinal microbiota composition and metabolism. Observed associations between IP, the pre-stress microbiota, and microbiota metabolites suggest targeting the intestinal microbiota could provide novel strategies for preserving IP during physiologic stress. PMID: 28336545 [PubMed - as supplied by publisher]

Related Articles A Community Multi-Omics Approach towards the Assessment of Surface Water Quality in an Urban River System. Int J Environ Res Public Health. 2017 Mar 14;14(3): Authors: Beale DJ, Karpe AV, Ahmed W, Cook S, Morrison PD, Staley C, Sadowsky MJ, Palombo EA Abstract A multi-omics approach was applied to an urban river system (the Brisbane River (BR), Queensland, Australia) in order to investigate surface water quality and characterize the bacterial population with respect to water contaminants. To do this, bacterial metagenomic amplicon-sequencing using Illumina next-generation sequencing (NGS) of the V5-V6 hypervariable regions of the 16S rRNA gene and untargeted community metabolomics using gas chromatography coupled with mass spectrometry (GC-MS) were utilized. The multi-omics data, in combination with fecal indicator bacteria (FIB) counts, trace metal concentrations (by inductively coupled plasma mass spectrometry (ICP-MS)) and in-situ water quality measurements collected from various locations along the BR were then used to assess the health of the river ecosystem. Sites sampled represented the transition from less affected (upstream) to polluted (downstream) environments along the BR. Chemometric analysis of the combined datasets indicated a clear separation between the sampled environments. Burkholderiales and Cyanobacteria were common key factors for differentiation of pristine waters. Increased sugar alcohol and short-chain fatty acid production was observed by Actinomycetales and Rhodospirillaceae that are known to form biofilms in urban polluted and brackish waters. Results from this study indicate that a multi-omics approach enables a deep understanding of the health of an aquatic ecosystem, providing insight into the bacterial diversity present and the metabolic output of the population when exposed to environmental contaminants. PMID: 28335448 [PubMed - in process]

Related Articles Revisiting the Metabolism and Bioactivation of Ketoconazole in Human and Mouse Using Liquid Chromatography-Mass Spectrometry-Based Metabolomics. Int J Mol Sci. 2017 Mar 13;18(3): Authors: Kim JH, Choi WG, Lee S, Lee HS Abstract Although ketoconazole (KCZ) has been used worldwide for 30 years, its metabolic characteristics are poorly described. Moreover, the hepatotoxicity of KCZ limits its therapeutic use. In this study, we used liquid chromatography-mass spectrometry-based metabolomics to evaluate the metabolic profile of KCZ in mouse and human and identify the mechanisms underlying its hepatotoxicity. A total of 28 metabolites of KCZ, 11 of which were novel, were identified in this study. Newly identified metabolites were classified into three categories according to the metabolic positions of a piperazine ring, imidazole ring, and N-acetyl moiety. The metabolic characteristics of KCZ in human were comparable to those in mouse. Moreover, three cyanide adducts of KCZ were identified in mouse and human liver microsomal incubates as "flags" to trigger additional toxicity study. The oxidation of piperazine into iminium ion is suggested as a biotransformation responsible for bioactivation. In summary, the metabolic characteristics of KCZ, including reactive metabolites, were comprehensively understood using a metabolomics approach. PMID: 28335386 [PubMed - in process]

Related Articles Vitamin E Nicotinate. Antioxidants (Basel). 2017 Mar 13;6(1): Authors: Duncan KR, Suzuki YJ Abstract Vitamin E refers to a family of compounds that function as lipid-soluble antioxidants capable of preventing lipid peroxidation. Naturally occurring forms of vitamin E include tocopherols and tocotrienols. Vitamin E in dietary supplements and fortified foods is often an esterified form of α-tocopherol, the most common esters being acetate and succinate. The vitamin E esters are hydrolyzed and converted into free α-tocopherol prior to absorption in the intestinal tract. Because its functions are relevant to many chronic diseases, vitamin E has been extensively studied in respect to a variety of diseases as well as cosmetic applications. The forms of vitamin E most studied are natural α-tocopherol and the esters α-tocopheryl acetate and α-tocopheryl succinate. A small number of studies include or focus on another ester form, α-tocopheryl nicotinate, an ester of vitamin E and niacin. Some of these studies raise the possibility of differences in metabolism and in efficacy between vitamin E nicotinate and other forms of vitamin E. Recently, through metabolomics studies, we identified that α-tocopheryl nicotinate occurs endogenously in the heart and that its level is dramatically decreased in heart failure, indicating the possible biological importance of this vitamin E ester. Since knowledge about vitamin E nicotinate is not readily available in the literature, the purpose of this review is to summarize and evaluate published reports, specifically with respect to α-tocopheryl nicotinate with an emphasis on the differences from natural α-tocopherol or α-tocopheryl acetate. PMID: 28335380 [PubMed - in process]

Related Articles Strategies for metabolite profiling based on liquid chromatography. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Feb 15;1044-1045:103-111 Authors: Saurina J, Sentellas S Abstract This paper aims at covering the principal strategies based on liquid chromatography (LC) for metabolite profiling in the field of drug discovery and development. The identification of metabolites generated in the organism is an important task during the early stages of preclinical research to define the most proper strategy for optimizing, adjusting metabolic clearance and minimizing bioactivation. An early assessment of the metabolite profile may be critical since metabolites can contribute to pharmacological and/or toxicological effects. The study of metabolites first involves their synthesis/generation and their further characterization and structural elucidation. For such a purpose, both in vitro and in vivo methods are commonly used for the generation of the corresponding metabolites. Next, analytical methods are used to tackle identification and characterization studies. Among the arsenal of techniques available in our labs, we will focus on LC, especially coupled to mass spectrometry (LC-MS), as one of the most powerful approaches for metabolite identification, characterization and quantification. Here, the topic of metabolite profiling based on LC will be addressed and representative examples of different possibilities will be discussed. PMID: 28088042 [PubMed - indexed for MEDLINE]

Related Articles Metabonomics study of the therapeutic mechanism of fenugreek galactomannan on diabetic hyperglycemia in rats, by ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Feb 15;1044-1045:8-16 Authors: Jiang W, Gao L, Li P, Kan H, Qu J, Men L, Liu Z, Liu Z Abstract Fenugreek is a traditional plant for the treatment of diabetes. Galactomannan, an active major component in fenugreek seeds, has shown hypoglycemic activity. The present study was performed to investigate the therapeutic mechanism underlying fenugreek galactomannan (F-GAL) in treating diabetes, using a metabonomics approach based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS). The F-GAL used for study was highly purified, and its yield, purity, and galactose/mannose ratio were characterized by capillary zone electrophoresis (CZE) and a modified phenol-sulfuric acid method. After treatment of streptozotocin (STZ)-induced diabetic rats with F-GAL for 28days, urine and serum samples were analyzed by UPLC-QTOF/MS. Multivariate statistical approaches such as principal component analysis (PCA) and orthogonal projection to latent structures squares-discriminant analysis (OPLS-DA) were applied to distinguish the non-diabetic/untreated, diabetic/untreated, and diabetic/F-GAL-treated groups. Then, potential biomarkers were identified that may help elucidate the underlying therapeutic mechanism of F-GAL in diabetes. The results demonstrated that there was a clear separation among the three groups in the PCA model. Fourteen potential biomarkers were identified by OPLS-DA, and they were determined to be produced in response to the therapeutic effects of F-GAL. These biomarkers were involved in histidine metabolism, tryptophan metabolism, energy metabolism, phenylalanine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, and arachidonic acid metabolism. In conclusion, our study demonstrates that a metabonomics approach is a powerful, novel tool that can be used to evaluate the underlying therapeutic mechanisms of herb extracts. PMID: 28063302 [PubMed - indexed for MEDLINE]

Related Articles Anti-Inflammation Effects and Potential Mechanism of Saikosaponins by Regulating Nicotinate and Nicotinamide Metabolism and Arachidonic Acid Metabolism. Inflammation. 2016 Aug;39(4):1453-61 Authors: Ma Y, Bao Y, Wang S, Li T, Chang X, Yang G, Meng X Abstract Inflammation is an important immune response; however, excessive inflammation causes severe tissue damages and secondary inflammatory injuries. The long-term and ongoing uses of routinely used drugs such as non-steroidal anti-inflammatory drugs (NSAIDS) are associated with serious adverse reactions, and not all patients have a well response to them. Consequently, therapeutic products with more safer and less adverse reaction are constantly being sought. Radix Bupleuri, a well-known traditional Chinese medicine (TCM), has been reported to have anti-inflammatory effects. However, saikosaponins (SS) as the main pharmacodynamic active ingredient, their pharmacological effects and action mechanism in anti-inflammation have not been reported frequently. This study aimed to explore the anti-inflammatory activity of SS and clarify the potential mechanism in acute inflammatory mice induced by subcutaneous injection of formalin in hind paws. Paw edema was detected as an index to evaluate the anti-inflammatory efficacy of SS. Then, a metabolomic method was used to investigate the changed metabolites and potential mechanism of SS. Metabolite profiling was performed by high-performance liquid chromatography combined with quadrupole time-of-flight mass spectrometry (HPLC-Q-TOF-MS). The detection and identification of the changed metabolites were systematically analyzed by multivariate data and pathway analysis. As a result, 12 different potential biomarkers associated with SS in anti-inflammation were identified, including nicotinate, niacinamide, arachidonic acid (AA), and 20-carboxy-leukotriene B4, which are associated with nicotinate and nicotinamide metabolism and arachidonic acid metabolism. The expression levels of biomarkers were effectively modulated towards the normal range by SS. It indicated that SS show their effective anti-inflammatory effects through regulating nicotinate and nicotinamide metabolism and arachidonic acid metabolism. PMID: 27251379 [PubMed - indexed for MEDLINE]

Related Articles HvPap-1 C1A Protease and HvCPI-2 Cystatin Contribute to Barley Grain Filling and Germination. Plant Physiol. 2016 04;170(4):2511-24 Authors: Diaz-Mendoza M, Dominguez-Figueroa JD, Velasco-Arroyo B, Cambra I, Gonzalez-Melendi P, Lopez-Gonzalvez A, Garcia A, Hensel G, Kumlehn J, Diaz I, Martinez M Abstract Proteolysis is an essential process throughout the mobilization of storage proteins in barley (Hordeum vulgare) grains during germination. It involves numerous types of enzymes, with C1A Cys proteases the most abundant key players. Manipulation of the proteolytic machinery is a potential way to enhance grain yield and quality, and it could influence the mobilization of storage compounds along germination. Transgenic barley plants silencing or over-expressing the cathepsin F-like HvPap-1 Cys protease show differential accumulation of storage molecules such as starch, proteins, and free amino acids in the grain. It is particularly striking that the HvPap-1 artificial microRNA lines phenotype show a drastic delay in the grain germination process. Alterations to the proteolytic activities in the over-expressing and knock-down grains associated with changes in the level of expression of several C1A peptidases were also detected. Similarly, down-regulating cystatin Icy-2, one of the proteinaceous inhibitors of the cathepsin F-like protease, also has important effects on grain filling. However, the ultimate physiological influence of manipulating a peptidase or an inhibitor cannot be always predicted, since the plant tries to compensate the modified proteolytic effects by modulating the expression of some other peptidases or their inhibitors. PMID: 26912343 [PubMed - indexed for MEDLINE]

Novel UCHL1 mutations reveal new insights into ubiquitin processing. Hum Mol Genet. 2017 Mar 09;: Authors: Rydning SL, Backe PH, Sousa MM, Iqbal Z, Øye AM, Sheng Y, Yang M, Lin X, Slupphaug G, Nordenmark TH, Vigeland MD, Bjørås M, Tallaksen CM, Selmer KK PMID: 28334853 [PubMed - as supplied by publisher]

Metabolomics of Pichia pastoris: Impact of buffering conditions on the kinetics and nature of metabolite loss during quenching. FEMS Yeast Res. 2017 Mar 15;: Authors: Mattanovich M, Rußmayer H, Scharl-Hirsch T, Puxbaum V, Burgard J, Mattanovich D, Hann S Abstract Mass spectrometry based metabolomic profiling is a powerful strategy to quantify the concentrations of numerous primary metabolites in parallel. To avoid distortion of metabolite concentrations, quenching is applied to stop the cellular metabolism instantly. For yeasts, cold methanol quenching is accepted to be the most suitable method to stop metabolism, while keeping the cells intact for separation from the supernatant. During this treatment, metabolite loss may occur while the cells are suspended in the quenching solution. An experiment for measuring the time dependent loss of selected primary metabolites in differently buffered quenching solutions was conducted to study pH and salt concentration dependent effects. Molecular properties of the observed metabolites were correlated with the kinetics of loss to gain insight into the mechanisms of metabolite leakage. Size and charge related properties play a major role in controlling metabolite loss. We found evidence that interaction with the cell wall is the main determinant to retain a molecule inside the cell. Besides suggesting an improved quenching protocol to keep loss at a minimum, we could establish a more general understanding of the process of metabolite loss during quenching, which will allow to predict optimal conditions for hitherto not analysed metabolites. PMID: 28334329 [PubMed - as supplied by publisher]

MetCCS Predictor: a web server for predicting collision cross-section values of metabolites in ion mobility-mass spectrometry based metabolomics. Bioinformatics. 2017 Mar 11;: Authors: Zhou Z, Xiong X, Zhu ZJ Abstract Summary: In metabolomics, rigorous structural identification of metabolites presents a challenge for bioinformatics. The use of collision cross-section (CCS) values of metabolites derived from ion mobility-mass spectrometry effectively increases the confidence of metabolite identification, but this technique suffers from the limit number of available CCS values. Currently, there is no software available for rapidly generating the metabolites' CCS values. Here, we developed the first web server, namely, MetCCS Predictor, for predicting CCS values. It can predict the CCS values of metabolites using molecular descriptors within a few seconds. Common users with limited background on bioinformatics can benefit from this software and effectively improve the metabolite identification in metabolomics. Availability: The web server is freely available at: http://www.metabolomics-shanghai.org/MetCCS. Contact: jiangzhu@sioc.ac.cn. Supplementary information: Supplementary data are available at Bioinformatics online. PMID: 28334295 [PubMed - as supplied by publisher]

Coordinated nitrogen and carbon remobilization for nitrate assimilation in leaf, sheath and root and associated cytokinin signals during early regrowth of Lolium perenne. Ann Bot. 2017 Mar 14;: Authors: Roche J, Turnbull MH, Guo Q, Novák O, Späth J, Gieseg SP, Jameson PE, Love J Abstract Background and Aims: The efficiency of N assimilation in response to defoliation is a critical component of plant regrowth and forage production. The aim of this research was to test the effect of the internal C/N balance on NO3- assimilation and to estimate the associated cytokinin signals following defoliation of perennial ryegrass ( Lolium perenne L. 'Grasslands Nui') plants. Methods: Plants, manipulated to have contrasting internal N content and contrasting availability of water soluble carbohydrates (WSCs), were obtained by exposure to either continuous light or short days (8:16 h light-dark), and watered with modified N-free Hoagland medium containing either high (5 m m ) or low (50 μ m ) NO3- as sole N source. Half of the plants were defoliated and the root, sheath and leaf tissue were harvested at 8, 24 and 168 h after cutting. The spatiotemporal changes in WSCs, synthesis of amino acids and associated cytokinin content were recorded after cutting. Key Results: Leaf regrowth following defoliation involved changes in the low- and high-molecular weight WSCs. The extent of the changes and the partitioning of the WSC following defoliation were dependant on the initial WSC levels and the C and N availability. Cytokinin levels varied in the sheath and root as early as 8 h following defoliation and preceded an overall increase in amino acids at 24 h. Subsequently, negative feedback brought the amino acid response back towards pre-defoliation levels within 168 h after cutting, a response that was under control of the C/N ratio. Conclusions: WSC remobilization in the leaf is coordinated with N availability to the root, potentially via a systemic cytokinin signal, leading to efficient N assimilation in the leaf and the sheath tissues and to early leaf regrowth following defoliation. PMID: 28334245 [PubMed - as supplied by publisher]

Bioenergetics-based modeling of Plasmodium falciparum metabolism reveals its essential genes, nutritional requirements, and thermodynamic bottlenecks. PLoS Comput Biol. 2017 Mar;13(3):e1005397 Authors: Chiappino-Pepe A, Tymoshenko S, Ataman M, Soldati-Favre D, Hatzimanikatis V Abstract Novel antimalarial therapies are urgently needed for the fight against drug-resistant parasites. The metabolism of malaria parasites in infected cells is an attractive source of drug targets but is rather complex. Computational methods can handle this complexity and allow integrative analyses of cell metabolism. In this study, we present a genome-scale metabolic model (iPfa) of the deadliest malaria parasite, Plasmodium falciparum, and its thermodynamics-based flux analysis (TFA). Using previous absolute concentration data of the intraerythrocytic parasite, we applied TFA to iPfa and predicted up to 63 essential genes and 26 essential pairs of genes. Of the 63 genes, 35 have been experimentally validated and reported in the literature, and 28 have not been experimentally tested and include previously hypothesized or novel predictions of essential metabolic capabilities. Without metabolomics data, four of the genes would have been incorrectly predicted to be non-essential. TFA also indicated that substrate channeling should exist in two metabolic pathways to ensure the thermodynamic feasibility of the flux. Finally, analysis of the metabolic capabilities of P. falciparum led to the identification of both the minimal nutritional requirements and the genes that can become indispensable upon substrate inaccessibility. This model provides novel insight into the metabolic needs and capabilities of the malaria parasite and highlights metabolites and pathways that should be measured and characterized to identify potential thermodynamic bottlenecks and substrate channeling. The hypotheses presented seek to guide experimental studies to facilitate a better understanding of the parasite metabolism and the identification of targets for more efficient intervention. PMID: 28333921 [PubMed - in process]

Exploring the human microbiome from multiple perspectives: factors altering its composition and function. FEMS Microbiol Rev. 2017 Feb 25;: Authors: Rojo D, Méndez-García C, Raczkowska BA, Bargiela R, Moya A, Ferrer M, Barbas C Abstract Our microbiota presents peculiarities and characteristics that may be altered by multiple factors. The degree and consequences of these alterations depend on the nature, strength and duration of the perturbations as well as the structure and stability of each microbiota. The aim of this review is to sketch a very broad picture of the factors commonly influencing different body sites, and which have been associated with alterations in the human microbiota in terms of composition and function. To do so, first, a graphical representation of bacterial, fungal and archaeal genera reveals possible associations among genera affected by different factors. Then, the revision of sequence-based predictions provides associations with functions that become part of the active metabolism. Finally, examination of microbial metabolite contents and fluxes reveals whether metabolic alterations are a reflection of the differences observed at the level of population structure, and in the last step, link microorganisms to functions under perturbations that differ in nature and aetiology. The utilisation of complementary technologies and methods, with a special focus on metabolomics research, is thoroughly discussed to obtain a global picture of microbiota composition and microbiome function and to convey the urgent need for the standardisation of protocols. PMID: 28333226 [PubMed - as supplied by publisher]

Effects of diet quality and psychosocial stress on the metabolic profiles of mice. J Proteome Res. 2017 Mar 23;: Authors: Goto T, Tomonaga S, Toyoda A Abstract There has been an increasing interest in relationship between stress and diet. To address this relationship, we evaluated an animal model of depression: male C57BL/6J mice subjected to subchronic mild social defeat stress (sCSDS) for 10 consecutive days using male ICR mice under two different calorie-adjusted diets conditions-non-purified (MF) and semi-purified (AIN) diets made from natural and chemical ingredients mainly, respectively. Our previous study indicates diet quality and purity affect stress susceptibility in sCSDS mice. We therefore hypothesized there are some key peripheral metabolites to change stress susceptible behavior. GC/MS metabolomics of plasma, liver, and cecal content were performed on four test groups: sCSDS + AIN diet (n = 7), sCSDS + MF diet (n = 6), control (no sCSDS) + AIN diet (n = 8), and control + MF diet (n = 8). Metabolome analyses revealed the number of metabolites changed by food was larger than the number changed by stress in all tissues. Enrichment analysis of the liver metabolite set altered by food implies that stress susceptible mice show increased glycolysis-related substrates in the liver. We found metabolites that were affected by stress (e.g., plasma and liver 4-hydroxyproline and plasma beta-alanine are higher in sCSDS than in control) and a stress × food interaction (e.g., plasma GABA is lower in sCSDS + AIN than in sCSDS + MF). Because functional compounds were altered by both stress and food, diet may be able to attenuate various stress-induced symptoms by changing metabolites in peripheral tissues. PMID: 28332841 [PubMed - as supplied by publisher]

Odd Chain Fatty Acids; New Insights of the Relationship Between the Gut Microbiota, Dietary Intake, Biosynthesis and Glucose Intolerance. Sci Rep. 2017 Mar 23;7:44845 Authors: Jenkins BJ, Seyssel K, Chiu S, Pan PH, Lin SY, Stanley E, Ament Z, West JA, Summerhill K, Griffin JL, Vetter W, Autio KJ, Hiltunen K, Hazebrouck S, Stepankova R, Chen CJ, Alligier M, Laville M, Moore M, Kraft G, Cherrington A, King S, Krauss RM, de Schryver E, Van Veldhoven PP, Ronis M, Koulman A Abstract Recent findings have shown an inverse association between circulating C15:0/C17:0 fatty acids with disease risk, therefore, their origin needs to be determined to understanding their role in these pathologies. Through combinations of both animal and human intervention studies, we comprehensively investigated all possible contributions of these fatty acids from the gut-microbiota, the diet, and novel endogenous biosynthesis. Investigations included an intestinal germ-free study and a C15:0/C17:0 diet dose response study. Endogenous production was assessed through: a stearic acid infusion, phytol supplementation, and a Hacl1(-/-) mouse model. Two human dietary intervention studies were used to translate the results. Finally, a study comparing baseline C15:0/C17:0 with the prognosis of glucose intolerance. We found that circulating C15:0/C17:0 levels were not influenced by the gut-microbiota. The dose response study showed C15:0 had a linear response, however C17:0 was not directly correlated. The phytol supplementation only decreased C17:0. Stearic acid infusion only increased C17:0. Hacl1(-/-) only decreased C17:0. The glucose intolerance study showed only C17:0 correlated with prognosis. To summarise, circulating C15:0 and C17:0 are independently derived; C15:0 correlates directly with dietary intake, while C17:0 is substantially biosynthesized, therefore, they are not homologous in the aetiology of metabolic disease. Our findings emphasize the importance of the biosynthesis of C17:0 and recognizing its link with metabolic disease. PMID: 28332596 [PubMed - in process]

Related Articles The use of on-line SFE-SFC/MS/MS to analyze disease biomarkers in dried serum spots compared with serum analysis using LC/MS/MS. Rapid Commun Mass Spectrom. 2017 Mar 23;: Authors: Suzuki M, Nishiumi S, Kobayashi T, Sakai A, Iwata Y, Uchikata T, Izumi Y, Azuma T, Bamba T, Yoshida M Abstract RATIONALE: The analytical stability and throughput of biomarker assays based on dried serum spots (DSS) are strongly dependent on the extraction process and determination method. In the present study, an on-line system based on supercritical fluid extraction-supercritical fluid chromatography coupled with tandem mass spectrometry (SFE-SFC/MS/MS) was established for analyzing the levels of disease biomarkers in DSS. METHODS: The chromatographic conditions were investigated using the ODS-EP, diol, and SIL-100A columns. Then, we optimized the SFE-SFC/MS/MS method using the diol column, focusing on candidate biomarkers of oral, colorectal, and pancreatic cancer that were identified using liquid chromatography (LC)/MS/MS. RESULTS: By using this system, 4 hydrophilic metabolites and 17 hydrophobic metabolites were simultaneously detected within 15 min. In an experiment involving clinical samples, PC 16:0-18:2/16:1-18:1 exhibited 93.8% sensitivity and 64.3% specificity, whereas PC 17:1-18:1/17:0-18:2 showed 81.3% sensitivity and 92.9% specificity for detecting oral cancer. In addition, assessments of the creatine levels demonstrated 92.3% sensitivity and 78.6% specificity for detecting colorectal cancer. CONCLUSIONS: The results of this study indicate that our method has great potential for clinical diagnosis and would be suitable for large-scale screening. PMID: 28332299 [PubMed - as supplied by publisher]

Related Articles Corrigendum: Chronic Pyruvate Supplementation Increases Exploratory Activity and Brain Energy Reserves in Young and Middle-Aged Mice. Front Aging Neurosci. 2017;9:67 Authors: Koivisto H, Leinonen H, Puurula M, Hafez HS, Alquicer Barrera G, Stridh MH, Waagepetersen HS, Tiainen M, Soininen P, Zilberter Y, Tanila H Abstract [This corrects the article on p. 41 in vol. 8, PMID: 27014054.]. PMID: 28331485 [PubMed - in process]

Related Articles Erratum to 'Cessation of biomechanical stretch model of C2C12 cells modelsmyocyte atrophy and anaplerotic changes in metabolism usingnon-targeted metabolomics analysisAmro' [Int. J. Biochem. Cell Biol. (2016) 80-92]. Int J Biochem Cell Biol. 2017 Mar 19;: Authors: Ilaiwy A, Quintana MT, Bain JR, Muehlbauer MJ, Brown DI, Stansfield WE, Willis MS PMID: 28330772 [PubMed - as supplied by publisher]