102 research outputs found
MetExploreViz: web component for interactive metabolic network visualization
Summary: MetExploreViz is an open source web component that can be easily embedded in any
web site. It provides features dedicated to the visualization of metabolic networks and pathways
and thus offers a flexible solution to analyse omics data in a biochemical context.
Availability and implementation: Documentation and link to GIT code repository (GPL 3.0 license)
are available at this URL: http://metexplore.toulouse.inra.fr/metexploreViz/doc
A computational solution to automatically map metabolite libraries in the context of genome scale metabolic networks
This article describes a generic programmatic method for mapping chemical compound libraries on organism-specific metabolic networks from various databases (KEGG, BioCyc) and flat file formats (SBML and Matlab files). We show how this pipeline was successfully applied to decipher the coverage of chemical libraries set up by two metabolomics facilities MetaboHub (French National infrastructure for metabolomics and fluxomics) and Glasgow Polyomics (GP) on the metabolic networks available in the MetExplore web server. The present generic protocol is designed to formalize and reduce the volume of information transfer between the library and the network database. Matching of metabolites between libraries and metabolic networks is based on InChIs or InChIKeys and therefore requires that these identifiers are specified in both libraries and networks. In addition to providing covering statistics, this pipeline also allows the visualization of mapping results in the context of metabolic networks. In order to achieve this goal, we tackled issues on programmatic interaction between two servers, improvement of metabolite annotation in metabolic networks and automatic loading of a mapping in genome scale metabolic network analysis tool MetExplore. It is important to note that this mapping can also be performed on a single or a selection of organisms of interest and is thus not limited to large facilities
The Dividing Line between Federal and State Promotion of Aeronautics
<p>The model xeno-estrogen bisphenol A (BPA) has been extensively studied over the past two decades, contributing to major advances in the field of endocrine disrupting chemicals research. Besides its well documented adverse effects on reproduction and development observed in rodents, latest studies strongly suggest that BPA disrupts several endogenous metabolic pathways, with suspected steatogenic and obesogenic effects. BPA's adverse effects on reproduction are attributed to its ability to activate estrogen receptors (ERs), but its effects on metabolism and its mechanism(s) of action at low doses are so far only marginally understood. Metabolomics based approaches are increasingly used in toxicology to investigate the biological changes induced by model toxicants and chemical mixtures, to identify markers of toxicity and biological effects. In this study, we used proton nuclear magnetic resonance (<sup>1</sup>H-NMR) based untargeted metabolite profiling, followed by multivariate statistics and computational analysis of metabolic networks to examine the metabolic modulation induced in human hepatic cells (HepG2) by an exposure to low and very low doses of BPA (10<sup>â6</sup>M, 10<sup>â9</sup>M, and 10<sup>â12</sup>M), vs. the female reference hormone 17ÎČ-estradiol (E2, 10<sup>â9</sup>M, 10<sup>â12</sup>M, and 10<sup>â15</sup>M). Metabolomic analysis combined to metabolic network reconstruction highlighted different mechanisms at lower doses of exposure. At the highest dose, our results evidence that BPA shares with E2 the capability to modulate several major metabolic routes that ensure cellular functions and detoxification processes, although the effects of the model xeno-estrogen and of the natural hormone can still be distinguished.</p
Challenges and perspectives for naming lipids in the context of lipidomics
Introduction: Lipids are key compounds in the study of metabolism and are increasingly studied in biology projects. It is a very broad family that encompasses many compounds, and the name of the same compound may vary depending on the community where they are studied. Objectives: In addition, their structures are varied and complex, which complicates their analysis. Indeed, the structural resolution does not always allow a complete level of annotation so the actual compound analysed will vary from study to study and should be clearly stated. For all these reasons the identification and naming of lipids is complicated and very variable from one study to another, it needs to be harmonized. Methods & Results: In this position paper we will present and discuss the different way to name lipids (with chemoinformatic and semantic identifiers) and their importance to share lipidomic results. Conclusion: Homogenising this identification and adopting the same rules is essential to be able to share data within the community and to map data on functional networks
The Nature of the Dietary Protein Impacts the Tissue-to-Diet 15N Discrimination Factors in Laboratory Rats
Due to the existence of isotope effects on some metabolic pathways of amino acid and protein metabolism, animal tissues are 15N-enriched relative to their dietary nitrogen sources and this 15N enrichment varies among different tissues and metabolic pools. The magnitude of the tissue-to-diet discrimination (Î15N) has also been shown to depend on dietary factors. Since dietary protein sources affect amino acid and protein metabolism, we hypothesized that they would impact this discrimination factor, with selective effects at the tissue level. To test this hypothesis, we investigated in rats the influence of a milk or soy protein-based diet on Î15N in various nitrogen fractions (urea, protein and non-protein fractions) of blood and tissues, focusing on visceral tissues. Regardless of the diet, the different protein fractions of blood and tissues were generally 15N-enriched relative to their non-protein fraction and to the diet (Î15N>0), with large variations in the Î15N between tissue proteins. Î15N values were markedly lower in tissue proteins of rats fed milk proteins compared to those fed soy proteins, in all sampled tissues except in the intestine, and the amplitude of Î15N differences between diets differed between tissues. Both between-tissue and between-diet Î15N differences are probably related to modulations of the relative orientation of dietary and endogenous amino acids in the different metabolic pathways. More specifically, the smaller Î15N values observed in tissue proteins with milk than soy dietary protein may be due to a slightly more direct channeling of dietary amino acids for tissue protein renewal and to a lower recycling of amino acids through fractionating pathways. In conclusion, the present data indicate that natural Î15N of tissue are sensitive markers of the specific subtle regional modifications of the protein and amino acid metabolism induced by the protein dietary source
Les abondances naturelles des isotopes stables de l'azote chez le rat : facteurs de variabilité et application pour l'étude des flux azotés et de l'impact métabolique de conditions nutritionnelles et physiopathologiques par modélisation compartimentale.
Natural abundances of stable nitrogen isotopes vary among tissues within an individual and among individuals within a population, and these differences are linked to the structural and functioning characteristics of the nitrogen metabolism and also to its modulations in response to variations in nutritional and physiological conditions. In this thesis, we developed an approach combining both experimentation and modeling, in order to better characterize and understand the modulations in the ÎŽ15N values of various nitrogen metabolic pools, and to show the capacity of the ÎŽ15N to provide information regarding the values and modulations of the body nitrogen fluxes, that are still poorly determined. We first measured the ÎŽ15N in various tissues (intestine, liver, plasma, muscle, kidney, skin ...) and in various nitrogen fractions (amino acids, proteins, urea, NH4) in rats, under different nutritional (i.e. in rats fed with P of distinct quality, that were milk and soy P) or pathophysiological (i.e. in rats that had or not become obese and insulin resistant after being fed a high-fat diet for 10 weeks). From these experimental data, we showed (i) that the tissue nitrogen discrimination (i.e., the difference between tissue and diet ÎŽ15N) is higher when the P is of lesser quality, and (ii) that, during the onset of a metabolic syndrome, in the presence of both insulin resistance and obesity, the ÎŽ15N differed in some nitrogen pools and thus constitute isotopic signatures of the metabolic impact of such conditions. In this thesis, we also measured the ÎŽ15N kinetics in the amino acid and protein fractions of several tissues after a shift in the diet ÎŽ15N. The analysis of these kinetics, using a compartimental modeling approach, enabled us to estimate tissue fractional turnover rates and to investigate the structure and the functioning of the protein synthesis and breakdown exchanges in some tissues and their level of compartmentation. Lastly, we developed a multi-compartmental model that describes the various body nitrogen transfers between and within tissues and accounts for the observed ÎŽ15N variability. This model of the nitrogen metabolism provides a new and systemic insight of the interactions and modulations of the various nitrogen fluxes, as opposed to the fragmented information available from the literature data. This model enabled us to reconstruct the mechanisms that caused the observed ÎŽ15N differences between nitrogen pools, to better understand how they vary, depending on which metabolic modulation and with which amplitude, and finally to hypothesize which nitrogen fluxes alterations are the more likely to be responsible for the ÎŽ15N variations that we observed in our experimentations. In conclusion, our experimental and modelling results show that it is feasible to gain information from the ÎŽ15N values regarding the metabolic nitrogen fluxes and their modulations, and highlight the interest of this new approach to get an integrated insight into the complex nitrogen metabolic system and a better understanding of the way the various between and within tissues nitrogen fluxes are regulated and altered.Les abondances relatives naturelles des diffĂ©rents isotopes stables de l'azote (ÎŽ15N) varient selon les tissus au sein d'un individu et selon les individus au sein d'une population, et ces diffĂ©rences reflĂštent Ă la fois les caractĂ©ristiques de structure et de fonctionnement du mĂ©tabolisme azotĂ© et ses modulations en lien avec des variations des conditions nutritionnelles et physio-pathologiques. Cette thĂšse vise, Ă travers une approche couplĂ©e d'expĂ©rimentation et de modĂ©lisation, Ă mieux caractĂ©riser et comprendre les modulations des ÎŽ15N des diffĂ©rents pools azotĂ©s et Ă dĂ©montrer la capacitĂ© des ÎŽ15N Ă fournir des informations sur les flux azotĂ©s de l'organisme, leurs valeurs et modulations, qui sont encore mal connus. Nous avons, dans un premier temps, mesurĂ© les ÎŽ15N dans plusieurs tissus (intestin, foie, plasma, muscles, rein, peau...) et dans diffĂ©rentes fractions azotĂ©es (acides aminĂ©s, protĂ©ines, urĂ©e, NH4) chez le rat, dans diffĂ©rentes conditions nutritionnelles (chez des rats nourris avec des P de qualitĂ© diffĂ©rente, les protĂ©ines de lait et de soja) ou physiopathologiques (chez des rats prĂ©sentant ou non un syndrome mĂ©tabolique, associant insulino-rĂ©sistance et obĂ©sitĂ©, aprĂšs avoir consommĂ© un mĂȘme rĂ©gime potentiellement obĂ©sogĂšne). Ces donnĂ©es expĂ©rimentales nous ont permis (i) de montrer que l'Ă©cart de ÎŽ15N entre les protĂ©ines tissulaires et le rĂ©gime est plus important lorsque la qualitĂ© protĂ©ique est moindre, et (ii) de mettre en Ă©vidence que, lors de l'initiation prĂ©coce d'un syndrome mĂ©tabolique associant insulino-rĂ©sistance et obĂ©sitĂ©, les ÎŽ15N de certains pools mĂ©taboliques sont modulĂ©s et constituent des signatures isotopiques des modulations mĂ©taboliques associĂ©es. Par ailleurs, grĂące Ă l'analyse par modĂ©lisation compartimentale des cinĂ©tiques de ÎŽ15N mesurĂ©es expĂ©rimentalement dans les fractions acides aminĂ©s et protĂ©ines de diffĂ©rents tissus aprĂšs augmentation du ÎŽ15N du rĂ©gime, nous avons pu estimer les taux de renouvellement protĂ©ique tissulaires et explorer la structure et le fonctionnement des Ă©changes entre acides aminĂ©s et protĂ©ines des diffĂ©rents tissus et comparer leur degrĂ© de compartimentation. Enfin, nous avons dĂ©veloppĂ© un modĂšle multi-compartimental reproduisant l'ensemble des flux azotĂ©s inter- et intra-organes de l'organisme et rendant compte des variations de ÎŽ15N observĂ©es. Cette reprĂ©sentation globale du mĂ©tabolisme azotĂ© fournit une vision novatrice du fonctionnement intĂ©grĂ© du mĂ©tabolisme azotĂ© dont les donnĂ©es Ă©parses de la littĂ©rature ne donnaient auparavant qu'une vision parcellaire et fragmentĂ©e. Le modĂšle a permis de reconstituer les mĂ©canismes qui conduisent Ă l'observation de diffĂ©rences de ÎŽ15N entre pools azotĂ©s, de mieux comprendre quelles modulations sont les plus susceptibles d'affecter les ÎŽ15N, avec quelle amplitude et dans quel sens, et finalement d'expliquer les variations de ÎŽ15N mises en Ă©vidence expĂ©rimentalement en terme de modulation des flux azotĂ©s. L'ensemble de nos rĂ©sultats d'expĂ©rimentation et de modĂ©lisation dĂ©montre la capacitĂ© des ÎŽ15N Ă apporter des informations sur les flux mĂ©taboliques azotĂ©s et souligne l'intĂ©rĂȘt prometteur de cette approche nouvelle pour acquĂ©rir une comprĂ©hension intĂ©grĂ©e du systĂšme complexe du mĂ©tabolisme azotĂ© inter- et intra-organes et des processus homĂ©ostatiques qui le rĂ©gulent et de ses dĂ©rĂ©gulations prĂ©-pathologiques
Natural abundances of stable nitrogen isotopes in rats : their variability and application for the study of body nitrogen fluxes and of the metabolic impact of nutritional and pathophysiological conditions using compartmental modeling.
Les abondances relatives naturelles des diffĂ©rents isotopes stables de l'azote (ÎŽ15N) varient selon les tissus au sein d'un individu et selon les individus au sein d'une population, et ces diffĂ©rences reflĂštent Ă la fois les caractĂ©ristiques de structure et de fonctionnement du mĂ©tabolisme azotĂ© et ses modulations en lien avec des variations des conditions nutritionnelles et physio-pathologiques. Cette thĂšse vise, Ă travers une approche couplĂ©e d'expĂ©rimentation et de modĂ©lisation, Ă mieux caractĂ©riser et comprendre les modulations des ÎŽ15N des diffĂ©rents pools azotĂ©s et Ă dĂ©montrer la capacitĂ© des ÎŽ15N Ă fournir des informations sur les flux azotĂ©s de l'organisme, leurs valeurs et modulations, qui sont encore mal connus. Nous avons, dans un premier temps, mesurĂ© les ÎŽ15N dans plusieurs tissus (intestin, foie, plasma, muscles, rein, peau...) et dans diffĂ©rentes fractions azotĂ©es (acides aminĂ©s, protĂ©ines, urĂ©e, NH4) chez le rat, dans diffĂ©rentes conditions nutritionnelles (chez des rats nourris avec des P de qualitĂ© diffĂ©rente, les protĂ©ines de lait et de soja) ou physiopathologiques (chez des rats prĂ©sentant ou non un syndrome mĂ©tabolique, associant insulino-rĂ©sistance et obĂ©sitĂ©, aprĂšs avoir consommĂ© un mĂȘme rĂ©gime potentiellement obĂ©sogĂšne). Ces donnĂ©es expĂ©rimentales nous ont permis (i) de montrer que l'Ă©cart de ÎŽ15N entre les protĂ©ines tissulaires et le rĂ©gime est plus important lorsque la qualitĂ© protĂ©ique est moindre, et (ii) de mettre en Ă©vidence que, lors de l'initiation prĂ©coce d'un syndrome mĂ©tabolique associant insulino-rĂ©sistance et obĂ©sitĂ©, les ÎŽ15N de certains pools mĂ©taboliques sont modulĂ©s et constituent des signatures isotopiques des modulations mĂ©taboliques associĂ©es. Par ailleurs, grĂące Ă l'analyse par modĂ©lisation compartimentale des cinĂ©tiques de ÎŽ15N mesurĂ©es expĂ©rimentalement dans les fractions acides aminĂ©s et protĂ©ines de diffĂ©rents tissus aprĂšs augmentation du ÎŽ15N du rĂ©gime, nous avons pu estimer les taux de renouvellement protĂ©ique tissulaires et explorer la structure et le fonctionnement des Ă©changes entre acides aminĂ©s et protĂ©ines des diffĂ©rents tissus et comparer leur degrĂ© de compartimentation. Enfin, nous avons dĂ©veloppĂ© un modĂšle multi-compartimental reproduisant l'ensemble des flux azotĂ©s inter- et intra-organes de l'organisme et rendant compte des variations de ÎŽ15N observĂ©es. Cette reprĂ©sentation globale du mĂ©tabolisme azotĂ© fournit une vision novatrice du fonctionnement intĂ©grĂ© du mĂ©tabolisme azotĂ© dont les donnĂ©es Ă©parses de la littĂ©rature ne donnaient auparavant qu'une vision parcellaire et fragmentĂ©e. Le modĂšle a permis de reconstituer les mĂ©canismes qui conduisent Ă l'observation de diffĂ©rences de ÎŽ15N entre pools azotĂ©s, de mieux comprendre quelles modulations sont les plus susceptibles d'affecter les ÎŽ15N, avec quelle amplitude et dans quel sens, et finalement d'expliquer les variations de ÎŽ15N mises en Ă©vidence expĂ©rimentalement en terme de modulation des flux azotĂ©s. L'ensemble de nos rĂ©sultats d'expĂ©rimentation et de modĂ©lisation dĂ©montre la capacitĂ© des ÎŽ15N Ă apporter des informations sur les flux mĂ©taboliques azotĂ©s et souligne l'intĂ©rĂȘt prometteur de cette approche nouvelle pour acquĂ©rir une comprĂ©hension intĂ©grĂ©e du systĂšme complexe du mĂ©tabolisme azotĂ© inter- et intra-organes et des processus homĂ©ostatiques qui le rĂ©gulent et de ses dĂ©rĂ©gulations prĂ©-pathologiques.Natural abundances of stable nitrogen isotopes vary among tissues within an individual and among individuals within a population, and these differences are linked to the structural and functioning characteristics of the nitrogen metabolism and also to its modulations in response to variations in nutritional and physiological conditions. In this thesis, we developed an approach combining both experimentation and modeling, in order to better characterize and understand the modulations in the ÎŽ15N values of various nitrogen metabolic pools, and to show the capacity of the ÎŽ15N to provide information regarding the values and modulations of the body nitrogen fluxes, that are still poorly determined. We first measured the ÎŽ15N in various tissues (intestine, liver, plasma, muscle, kidney, skin âŠ) and in various nitrogen fractions (amino acids, proteins, urea, NH4) in rats, under different nutritional (i.e. in rats fed with P of distinct quality, that were milk and soy P) or pathophysiological (i.e. in rats that had or not become obese and insulin resistant after being fed a high-fat diet for 10 weeks). From these experimental data, we showed (i) that the tissue nitrogen discrimination (i.e., the difference between tissue and diet ÎŽ15N) is higher when the P is of lesser quality, and (ii) that, during the onset of a metabolic syndrome, in the presence of both insulin resistance and obesity, the ÎŽ15N differed in some nitrogen pools and thus constitute isotopic signatures of the metabolic impact of such conditions. In this thesis, we also measured the ÎŽ15N kinetics in the amino acid and protein fractions of several tissues after a shift in the diet ÎŽ15N. The analysis of these kinetics, using a compartimental modeling approach, enabled us to estimate tissue fractional turnover rates and to investigate the structure and the functioning of the protein synthesis and breakdown exchanges in some tissues and their level of compartmentation. Lastly, we developed a multi-compartmental model that describes the various body nitrogen transfers between and within tissues and accounts for the observed ÎŽ15N variability. This model of the nitrogen metabolism provides a new and systemic insight of the interactions and modulations of the various nitrogen fluxes, as opposed to the fragmented information available from the literature data. This model enabled us to reconstruct the mechanisms that caused the observed ÎŽ15N differences between nitrogen pools, to better understand how they vary, depending on which metabolic modulation and with which amplitude, and finally to hypothesize which nitrogen fluxes alterations are the more likely to be responsible for the ÎŽ15N variations that we observed in our experimentations. In conclusion, our experimental and modelling results show that it is feasible to gain information from the ÎŽ15N values regarding the metabolic nitrogen fluxes and their modulations, and highlight the interest of this new approach to get an integrated insight into the complex nitrogen metabolic system and a better understanding of the way the various between and within tissues nitrogen fluxes are regulated and altered
How Does Your Body Deal With Fast-Food Meals?
International audienceEating a less-than-healthy diet can increase the chances of becoming obese, which usually happens when body organs have difficulties using or storing the excess fat and sugar that we eat. To better understand how what we eat affects the functioning of our organs, we measured substances called metabolites, which come from food, in the blood of obese minipigs. We then used computers to figure out what happens to these metabolites inside the liver following normal meals or a fast-food meal. We found that the liver fights against unhealthy food by finding ways to use or remove the excess fat and sugar. However, some of the paths normally followed by healthy food might become blocked when we eat too much unhealthy food. Our work showed that a better understanding of how the liver processes the metabolites from unhealthy diets could help people suffering from the effects of obesity
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