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Flexible Ignition System for a Gas TurbineBerg, Anton January 2012 (has links)
Siemens Industrial Turbomachinery AB produce five gas turbines models. The SGT-700 can currently only start on gases which contain low amounts of inert gases. It is therefore of interest to widen the fuel range which the SGT-700, as well as other gas turbines, can start on. This report investigates the maximum limit of inert gases the SGT-700 will be able to start on, but also investigates if it is possible to start on liquid fuel (diesel) by making a few modifications to the gas turbine. To investigate this, the atmospheric combustion rig available at Siemens in Finspång has been used with a standard burner, igniter and ignition unit for the SGT-700. For the liquid fuel, the igniter was replaced by a torch igniter specially made for liquid fuels. Four different gases were evaluated; methane, propane, CO2 and N2 in order to see the effect of both various hydrocarbons and various inert gases. A model was developed for the gaseous experiments to estimate the limit for the maximum amount of inert gases the gas turbine would be able to start on. The model suggested that CO2 would require a larger amount of energy than N2 for the same amount in the composition, but that varying hydrocarbons did not have any effect if looking at the mass % of inert gas in the composition. The model was also extended with ethane and hydrogen but no experiments were performed with these gases. The model gave satisfying results. It overestimated the maximum amount of inert gases which could be mixed with propane, but agreed well when comparing the two inert gases with each other. Other interesting results were that an increased fuel flow decreased the minimum ignition energy and that an increased air flow gave a minor decrease in the maximum amount of inert gases that was possible to ignite. The torch igniter for the liquid fuel worked in a satisfying way. The ignition energy was however too low, so the ignition reliability was low. A new ignition unit with larger energy output therefore needs to be implemented. The igniter was fairly insensitive to variations in burner air flow and the ignition delay was small enough to provide a sustainable flame.
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LIGHT ALKANE CONVERSION TO VALUABLE LIQUID HYDROCARBONS ON BIFUNCTIONAL CATALYSTS IN A SINGLE STEPChe-Wei Chang (12447201) 25 April 2022 (has links)
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<p>Cyclar process was previously developed to convert propane and butane into aromatics using gallium-promoted ZSM-5 zeolites (Ga/ZSM-5). However, it has two major limitations. Firstly, light gases (methane and ethane) limit the yield of higher molecular weight hydrocarbons for propane conversion. Secondly, ethane is unreactive on Ga/ZSM-5 catalysts. Relative rates and selectivity for propane conversion on two components, gallium (Ga/Al2O3) and acid ZSM-5 (H-ZSM-5) were investigated, and the results suggest that light gas was produced by propane monomolecular cracking on ZSM-5 due to the imbalance of alkane dehydrogenation and olefin conversion rates on two catalytic functions. A PtZn alloy catalyst, which has >99% propene selectivity and 30 times higher rate than Ga, was used for the dehydrogenation function. The bifunctional PtZn/SiO2+ZSM-5 catalyst has high yields of aromatics with low methane selectivity (<5%) at ~70% propane conversion. The results suggest methane can be minimized by utilizing the PtZn alloy and lowering the monomolecular cracking rate by ZSM-5. In addition, PtZn alloy increases aromatics selectivity. Aromatics formation pathway was investigated by studying the rate and selectivity of a model intermediate (cyclohexene) on ZSM-5, PtZn/SiO2 and Ga/Al2O3. Benzene is formed at similar rates on Ga/Al2O3 and ZSM-5 but cracking of cyclohexene on the latter is two orders of magnitude higher than the benzene formation rate, indicating cracking of cyclic hydrocarbons leads to low aromatization rate on Ga/ZSM-5. The benzene formation rate on the PtZn/SiO2 is 200 times higher than that on ZSM-5, suggesting aromatics are formed by the metal pathway on PtZn/SiO2+ZSM-5. </p>
<p>Unlike Ga/ZSM-5 catalysts, PtZn/SiO2+ZSM-5 catalysts also convert propane to aromatics at low temperature (350 ℃). The temperature effect on propane dehydroaromatization pathways on the PtZn/SiO2+ZSM-5 bifunctional catalysts was investigated to develop strategies for propane conversion to valuable liquid hydrocarbons. At high temperature (550 ℃), high dehydrogenation rates and lower monomolecular cracking rates are required to minimize methane formation, leading to primarily propene and BTX (benzene, toluene, and xylenes). By recycling propene in the propane conversion range of 30-45%, >80% BTX yields is likely achievable at full recycle. At mid temperature (400-450 ℃), the product has high selectivity to gasoline-blending hydrocarbons (butanes, C5+ hydrocarbons, toluene, and xylenes) at 15-25% propane conversions because dehydrogenation rates are moderately high, and oligomerization is more favored than cracking. At low temperature (350℃), ~25% propane conversion is achieved and has high selectivity (~60%) to butanes, but the propane conversion rates are likely too low to be practical. While methane formation by monomolecular cracking limits liquid yields at high reaction temperature, at mid and low temperatures, hydrogen co-produced at high propane conversions saturates light olefins to make undesired ethane, which becomes major yield-loss reaction on the PtZn/SiO2+ZSM-5. </p>
<p>Finally, PtZn/SiO2+ZSM-5 catalysts can convert ethane to C3+ and aromatics but the methane selectivity increases rapidly at high ethane conversion. The roles of two catalytic function (Pt-Zn alloy and ZSM-5) in the dehydroaromatization pathways of ethane and propane will be further studied and their product distribution will be compared to have better understandings on the differences in the dominant yield-loss reaction and dehydroaromatization pathways. </p>
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The Effect of Nitrogen Surface Ligands on Propane Metathesis: Design and Characterizations of N-modified SBA15-Supported Schrock-type Tungsten AlkylidyneEid, Ahmed A. 04 1900 (has links)
Catalysis, which is primarily a molecular phenomenon, is an important field of chemistry because it requires the chemical conversion of molecules into other molecules. It also has an effect on many fields, including, but not limited to, industry, environment and life Science[1].
Surface Organometallic Chemistry is an effective methodology for Catalysis as it imports the concept and mechanism of organometallic chemistry, to surface science and heterogeneous catalysis. So, it bridges the gap between homogenous and heterogeneous catalysis[1].
The aim of the present research work is to study the effect of Nitrogen surface ligands on the activity of Alkane, Propane in particular, metathesis. Our approach is based on the preparation of selectively well-defined group (VI) transition metal complexes supported onto mesoporous materials, SBA15 and bearing amido and/or imido ligands. We choose nitrogen ligands because, according to the literature, they showed in some cases better catalytic properties in homogenous catalysis in comparison with their oxygen counterparts[2].
The first section covers the modification of a highly dehydroxylated SBA15 surface using a controlled ammonia treatment. These will result in the preparation of two kind of Nitrogen surface ligands:
- One with vicinal silylamine/silanol, (≡SiNH2)(≡SiOH), noted [N,O]SBA15 and,
- Another one with vicinal bis-silylamine moieties (≡SiNH2)2, noted [N,N]SBA15[3].
The second section covers the reaction of Schrock type Tungsten Carbyne [W(≡C- tBu)(CH2-tBu)3] with those N-surface ligands and their characterizations by FT-IR, multiple quantum solid state NMR (1H, 13C), elemental analysis and gas phase analysis.
The third section covers the generation of the active site, tungsten hydride species. Their performance toward propane metathesis reaction using the dynamic reactor technique PID compared toward previous well-known catalysts supported on silica oxide or mesoporous materials[4].
A fairly good turn over number (TON = 43) has been obtained following hydrogen treatment of tungsten alkylidyne supported on [N,O] SBA151100, in comparison with TON of zero in the obtained with [N,N] SBA15 and classical SiO2 silica support. Therefore, the cooperation between silylamine and silanol in close vicinity are required to improve the efficiency of the catalyst in the metathesis of propane.
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PCR Primers for the Detection of Propane and Butane-Oxidizing MicroorganismsChan, Brian Jeremy 01 March 2011 (has links) (PDF)
In an increasingly energy-hungry world, our capacity to meet the heightened energy demands of the future has become a pressing matter. The most urgent of these concerns are tied to the accessibility of petroleum. Various experts have proselytized both the imminent arrival of peak oil production rates and the ensuing decline of those rates thereafter. And to that end, the development of novel and advanced oil exploration methodologies has become almost as important as finding the sources of oil themselves.
The soils above petroleum reservoirs play host to various communities of alkane- oxidizing bacteria that can utilize the natural gas emitted by the reservoirs as a source of carbon and energy. While methane can originate from non-petroleum sources, the only natural sources of propane and butane are oil and gas fields. The increased presence of propane and butane-oxidizing bacteria in a given soil sample is used by oil prospectors as an accurate indicator of a proximal petroleum reservoirs.
For over a century, cell counts and hydrocarbon metabolic rates have been the metrics used to determine the presence of hydrocarbon-oxidizing microbes. These methods require weeks to complete. Here, we have developed a set of DNA primers for a much more rapid detection of hydrocarbon-oxidizing microbes through PCR amplification - for the chief purpose of petroleum exploration. Each primer’s design is based on a nucleotide sequence alignment of seven prmA and bmoX genes from seven organisms, which encode the large hydroxylase subunit of propane monooxygenase and the alpha hydroxylase subunit of butane monooxygenase respectively. These monooxygenases are the enzymes responsible for the initiation of propane and butane catabolism. Optimization of PCR with this primer set was accomplished using DNA extracted from known butane and propane oxidizers as positive controls, and methane and toluene oxidizers as negative controls. PCR products recovered from cultures of butane-oxidizing and propane-oxidizing bacteria, and soil samples, were sequenced. Phylogenetic trees were constructed from the sequencing data to confirm the accuracy of amplification. We demonstrate the use of PCR and agarose gel electrophoresis to detect hydrocarbon-oxidizing bacteria in culture and in complex microbial soil communities. Detection limits were elucidated through two different experiments. Potential avenues of advancements include narrowing specificity by selectively removing primer degeneracies, the use of additional positive and negative controls and the adaptation of the primers to a qPCR TaqMan assay.
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MOLECULAR STRUCTURE-REACTIVITY RELATIONSHIPS FOR PROPANE OXIDATION OVER MODEL MIXED OXIDE CATALYSTSAL-SAEEDI, JAMAL N. 07 July 2003 (has links)
No description available.
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Forcefield-Based Simulations of Bulk Structure of Mo-V-(Te, Nb)-O M1 Phase Catalysts for Selective Propane Ammoxidation to AcrylonitrileKapustin, Yaroslav A. 20 April 2011 (has links)
No description available.
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The spectroscopic and structural characterization of chlorine modification of MoOx catalysts supported over silica/titania mixed oxides for the oxidative dehydrogenation of ethane and propaneLiu, Chang 12 October 2004 (has links)
No description available.
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Reduction of convective heat transfer from reacting flows by application of electric fieldsOakes, Brian K. 04 August 2009 (has links)
The electric field-induced reduction of heat transfer from a rod-stabilized diffusion flame and a step-stabilized premixed flame was investigated. The fuel examined was propane. Inlet velocity for the diffusion mode was a nominal value of 3.4 m/s with nominal air/fuel ratios of 420, 320, and 270. Inlet velocities ranged from 4.5 to 9.9 m/s for the premixed mode with equivalence ratios of 0.65 to 1.03. Maximum applied voltages for the diffusion and premixed modes were 8.0 and 6.6 kVDC, respectively. The field was applied in a direction perpendicular to the flow.
Heat transfer amelioration was quantified using records of temperature versus downstream distance from the stabilizer acquired for the external surface of the heatloaded electrode which was exposed to the ambient environment. In addition, shadowgraphs and photographs were used to observe any alteration of flame position or of the bulk flowfield. These observations were used to investigate mechanisms potentially responsible for heat transfer reduction.
The rod-stabilized diffusion mode displayed some field-induced reduction in heat transfer. Both bulk flow alteration and reduction in radiation (associated with soot) were concluded to be responsible. Flame impingement on the heat-loaded electrode was reduced by a field-induced increase in flow along the surface. Flame luminosity was reduced by the electric field (presumably due to a field-induced modification of soot production and/or destruction). This caused a reduction in radiative heat transfer.
No heat-transfer amelioration was noted for the premixed step-stabilized mode. This was attributed primarily to a geometry not accommodating to field-induced heat transfer reduction. Higher velocities and a lower presence of soot than the diffusion mode and problems associated with flame impingement on both electrodes (reduces maximum voltages and distorts field), also contributed to the negative result. Limited displacement of the luminous portion of the reaction zone was noted. / Master of Science
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High capacity heat pump development for sanitary hot water productionPitarch i Mocholí, Miquel 29 May 2017 (has links)
Heat pumps have been identified as an efficient alternative to traditional boilers for the production of sanitary hot water (SHW). The high water temperature lift (usually from 10ºC to 60ºC) involved in this application has conditioned the type of used solutions. On the one hand, transcritical cycles have been considered as one of the most suitable solutions to overcome the high water temperature lift. Nevertheless, the performance of the transcritical CO2 heat pump is quite dependent on the water inlet temperature, which in many cases is above 10ºC. Furthermore, performance highly depends on the rejection pressure, which needs to be controlled to work at the optimum point in any condition. On the other hand, for the subcritical systems, subcooling seems to be critical for the heat pump performance when working at high temperature lifts, but there is not any published work that optimizes subcooling in the SHW application for these systems. Therefore, the subcritical cycle should require a systematic study on the subcooling that optimizes COP depending on the external conditions, in the same way as it has been done for the rejection pressure in the transcritical cycle.
The aim of this thesis is to investigate the role of subcooling in the performance of a Propane water-to-water heat pump for SHW production, in the application of heat recovery from any water source. Two different approaches to overcome the high degree of subcooling were designed and built to test them in the laboratory:
1) Subcooling is made at the condenser: The active refrigerant charge of the system is controlled by a throttling valve. Subcooling is controlled independently at any external condition.
2) Subcooling is made in a separate heat exchanger, the subcooler. Subcooling is not controlled, it depends on the external condition and the heat transfer at the subcooler.
The heat pumps were tested at different water temperatures at the evaporator inlet (10ºC to 35ºC) and condenser inlet (10ºC to 55ºC), while the water production temperature was usually fixed to 60¿C. The obtained results have shown that COP depends strongly on subcooling. In the nominal condition (20¿C/15¿C for the inlet/outlet water temperature at the evaporator and 10ºC/60ºC for the inlet/outlet water temperature in the heat sink), the optimum subcooling was about 43 K with a heating COP of 5.61, which is about 31% higher than the same cycle working without subcooling. Furthermore, the system with subcooling has been proved experimentally as being capable of producing water up to 90¿C and has shown a higher COP than some CO2 commercial products (catalog data reference). / Las bombas de calor han sido identificadas como una alternativa eficaz a las calderas tradicionales para la producción de agua caliente sanitaria (ACS). El elevado salto de temperatura del agua que normalmente tiene lugar en esta aplicación (por lo general de 10ºC a 60ºC) ha condicionado el tipo de soluciones que se utilizan. Por un lado, los ciclos transcríticos han sido considerados como una de las mejores soluciones para trabajar con los elevados saltos de temperatura del agua. Sin embargo, el rendimiento de la bomba de calor transcrítica con CO2 es bastante dependiente de la temperatura de entrada del agua, que en muchos casos está por encima de los 10¿C. Además, el rendimiento depende en gran medida de la presión de descarga, la cual necesita ser controlada con el fin de trabajar en el punto óptimo en cualquier condición externa. Por otra parte, para los sistemas subcríticos, el subenfriamiento parece ser crítico para el buen funcionamiento de la bomba de calor cuando se trabaja con elevados saltos de temperatura del agua, pero no hay ningún trabajo publicado en el que optimicen el subenfriamiento para la aplicación de ACS en estos sistemas. Por lo tanto, los sistemas subcríticos requieren de un estudio sistemático para buscar el subcooling óptimo y maximizar el COP en función de las condiciones externas, de la misma forma que se ha hecho para la presión de descarga en los ciclos transcríticos.
El objetivo de esta tesis es investigar el papel del subenfriamiento en el rendimiento de una bomba de calor trabajando con Propano para la producción de ACS, en la aplicación de recuperación de calor de cualquier fuente de agua (agua- agua). Dos enfoques diferentes para superar el alto grado de subenfriamiento fueron diseñados y construidos para ponerlos a prueba en el laboratorio:
1) El subenfriamiento se hace en el condensador: La carga activa de refrigerante del sistema se controla con una válvula de estrangulación. De esta manera, el subenfriamiento puede ser controlado de forma independiente a cualquier condición externa.
2) El subenfriamiento se hace en un intercambiador de calor separado, el subenfriadador. El subenfriamiento no se controla, este depende de la condición externa y de la transferencia de calor en el subenfriadador.
Las bombas de calor se ensayaron a diferentes temperaturas del agua a la entrada del evaporador (10ºC a 35ºC) y entrada del condensador (10ºC a 55ºC), mientras que la temperatura de producción de agua, normalmente, se fija a 60¿C. Los resultados obtenidos han demostrado que el COP depende mucho del subenfriamiento. En las condiciones nominales (20ºC/15ºC para la temperatura del agua de entrada/salida en el evaporador y 10ºC/60ºC para la temperatura del agua de entrada/salida en el condensador), el subenfriamiento óptimo fue aproximadamente de 43 K con un COP de calentamiento de 5,61, que es alrededor del 31% más alto que el mismo ciclo trabajando sin subenfriamiento. Además, el sistema con subenfriamiento ha probado de forma experimental, que es capaz de producir agua hasta los 90ºC, y ha mostrado un COP más alto que algunos productos comerciales que trabajan con CO2 (datos de referencia del catálogo). / Les bombes de calor han estat identificades com una alternativa eficaç a les calderes tradicionals per a la producció d'aigua calenta sanitària (ACS). L'elevat salt de temperatura de l'aigua que normalment té lloc en aquesta aplicació (en general de 10ºC a 60ºC) ha condicionat el tipus de solucions que s'utilitzen. Per una banda, els cicles transcrítics s'han considerat com una de les millors solucions per tal de treballar amb els elevats salts de temperatura de l'aigua. No obstant això, el rendiment de la bomba de calor transcrítica amb CO2 és bastant dependent de la temperatura d'entrada de l'aigua, que en molts casos està per damunt de 10¿C. A més, el rendiment depèn en gran mesura de la pressió de descarrega, la qual necessita ser controlada per tal de treballar en el punt òptim a qualsevol condició externa. Per altra banda, per als sistemes subcrítics, el sub-refredament sembla ser crític per al funcionament de la bomba de calor quan es treballa amb elevats salts de temperatura de l'aigua, però no hi ha cap treball publicat en el qual optimitzen el sub-refredament per a l'aplicació d'ACS en aquests sistemes. Per tant, els sistemes subcrítics requereixen d'un estudi sistemàtic per tal de buscar el subcooling òptim i maximitzar el COP en funció de les condicions externes, en la mateixa forma que s'ha fet per la pressió de descarrega en els cicles transcrítics.
L'objectiu d'aquesta tesi és investigar el paper del sub-refredament en el rendiment d'una bomba de calor treballant amb Propà per a la producció d'ACS, en l'aplicació de recuperació de calor de qualsevol font d'aigua (aigua-aigua). Dos enfocaments diferents per tal de superar l'alt grau de sub-refredament van ser dissenyats i construïts per posar-los a prova en el laboratori:
1) El sub-refredament es fa en el condensador: La càrrega activa de refrigerant del sistema es controla amb una vàlvula d'estrangulació. D'aquesta manera, el sub-refredament pot ser controlat de forma independent en qualsevol condició externa.
2) El sub-refredament es fa en un intercanviador de calor separat, el sub-refredador. El sub-refredament no es controla, este depèn de la condició externa i de la transferència de calor al sub-refredador.
Les bombes de calor es van assajar a diferents temperatures de l'aigua a l'entrada de l'evaporador (10ºC a 35ºC) i a l'entrada del condensador (10ºC a 55ºC), mentre que la temperatura de producció d'aigua, normalment, es fixa a 60¿C. Els resultats obtinguts han demostrat que el COP depèn molt del sub-refredament. En les condicions nominals (20ºC/15ºC per a la temperatura de l'aigua d'entrada/eixida a l'evaporador i 10ºC/60ºC per a la temperatura de l'aigua d'entrada/eixida en el condensador), el sub-refredament òptim és aproximadament de 43 K amb un COP d'escalfament de 5,61, que és al voltant del 31% més alt que el mateix cicle treballant sense sub-refredament. A més, el sistema amb sub-refredament ha provat de forma experimental, que és capaç de produir aigua fins als 90ºC, i ha mostrat un COP més alt que alguns productes comercials que treballen amb CO2 (dades de referència del catàleg). / Pitarch I Mocholí, M. (2017). High capacity heat pump development for sanitary hot water production [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/81858
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Effect and Mechanisms of Action of Intestinal Bacteria and Bioactive Compounds on the Immune System and Metabolism in Obesity ModelsLiébana García, Rebeca 01 December 2025 (has links)
Tesis por compendio / [ES] La obesidad representa un importante reto para la salud pública debido a su elevada prevalencia y a las comorbilidades asociadas. Las dietas hipercalóricas activan el sistema inmunitario intestinal y alteran la microbiota intestinal causando daños metabólicos en el organismo. De hecho, la pérdida de homeostasis inmunológica intestinal se considera un evento que precede a la aparición de la inflamación sistémica de bajo grado asociada a la obesidad. Dado que la microbiota intestinal es un factor modificable, su modulación puede convertirse en una oportunidad para reducir el impacto de la obesidad. Por ello la identificación de los factores que participan en la respuesta inflamatoria a las dietas obesogénicas y la búsqueda de alternativas terapéuticas basadas en la microbiota constituyen una vía de investigación prometedora para combatir la obesidad. Esta Tesis Doctoral evalúa el potencial de nuevos probióticos y estrategias dietéticas para combatir la obesidad basadas en sus propiedades inmunomoduladoras.
En el Primer Capítulo investigamos el potencial anti-obesogénico del propil propano tiosulfinato (PTS), un compuesto organosulfurado derivado de la especie Allium, en dos dosis diferentes (0,1 o 1 mg/kg/día) utilizando un modelo murino de obesidad inducida por la dieta (DIO). Nuestros hallazgos demostraron los efectos protectores de PTS frente a la obesidad, ya que su administración redujo el peso corporal y mejoró la homeostasis de glucosa. En el tejido adiposo y el hígado, PTS redujo la inflamación y el metabolismo lipídico aberrante causado por la dieta obesogénica. Además, PTS incrementó la actividad termogénica en el tejido adiposo marrón y reforzó la función barrera intestinal. En vista de los modestos cambios en el ecosistema microbiano intestinal, concluimos que estos efectos no eran mediados por la microbiota.
En el Segundo Capítulo evaluamos el potencial anti-obesogénico y el mecanismo de acción de una nueva bacteria llamada Phascolarctobacterium faecium DSM 32890. Para ello, realizamos diferentes experimentos in vitro e in vivo usando diferentes cultivos celulares (macrófagos derivados de médula ósea y células linfoides innatas intestinales del grupo 1 (LC1s)) y modelos murinos DIO (ratones C57BL/6J y Rag1-/-). El tratamiento de ratones alimentados con una dieta hipercalórica con P. faecium incrementó la proporción de los macrófagos M2 en el intestino, lo que contrarrestó el aumento de ILC1s y, en última instancia, mitigó la intolerancia a la glucosa y el aumento de peso corporal, independientemente de la viabilidad de la bacteria. Además, P. faecium reforzó la función barrera intestinal y evitó la inflamación sistémica causada por la dieta hipercalórica. Estos beneficios metabólicos se mantuvieron en ausencia de inmunidad adaptativa, pero se perdieron cuando la bacteria se coadministró con un inhibidor (GW2580) de la polarización de macrófagos M2. Por último, realizamos un amplio estudio con datos metagenómicos de 6.361 personas que mostró una relación inversa entre P. faecium y la obesidad, independientemente de la nacionalidad, el sexo o la edad, lo que sugiere la asociación de esta bacteria con la salud metabólica.
En el Tercer Capítulo, investigamos la implicación de las ILC1s intestinales en la progresión de la obesidad y las alteraciones metabólicas asociadas. Para ello, evaluamos longitudinalmente la respuesta de las ILC1s y las consecuencias su depleción de ILC1s en un modelo murino DIO. En el intestino, el bloqueo de ILC1s evitó el aumento de macrófagos M1 e ILC2s y promovió la activación de la vía ILC3-IL22, aumentando la producción de mucina, la expresión de péptidos antimicrobianos y el número de células neuroendocrinas. Además, el bloqueo de ILC1s restableció el perfil microbiano y el metaboloma, acercándose al perfil asociado con la salud metabólica. En última instancia, estas mejoras se asociaron con una mayor secreción de hormonas intestinales, y una reducción de la insulinemia y la adiposidad. / [CA] L'obesitat és un repte per a la salut pública degut a la elevada prevalença i les comorbiditats. Les dietes hipercalòriques activen el sistema immunitari intestinal i alteren la microbiota intestinal causant danys metabòlics en l'organisme. De fet, la pèrdua d'homeòstasi immunològica a escala intestinal es considera un esdeveniment primerenc que precedeix l'aparició de la inflamació sistèmica de baix grau associada a l'obesitat. Atés que la microbiota intestinal és un factor modificable, la seua modulació pot convertir-se en una oportunitat per a reduir l'impacte de l'obesitat. Per això, la identificació dels factors que participen en la resposta inflamatòria a les dietes obesogèniques i la recerca d'alternatives terapèutiques basades en la microbiota son una via d'investigació prometedora per a combatre l'obesitat. Aquesta Tesi Doctoral avalua el potencial de nous probiòtics i estratègies dietètiques per a combatre l'obesitat basada en propietats immunomoduladores.
En el Primer Capítol investiguem el potencial anti-obesogènic del propil propà tiosulfat (PTS), un compost organosulfurat derivat de l'espècie Allium, en dues dosis diferents (0,1 o 1 mg/kg/dia) utilitzant un model murí d'obesitat induïda per la dieta. Els resultats demostren els efectes protectors de PTS enfront a l'obesitat, ja que la seua administració va reduir el pes corporal i va millorar l'homeòstasi de glucosa. En el teixit adipós i el fetge, PTS va prevenir l'augment de la resposta inflamatòria i les alteracions del metabolisme lipídic causades per la dieta hipercalòrica. A més, PTS va incrementar l'activitat termogènica en el teixit adipós marró i millorà la funció barrera intestinal alterats per la dieta. Observàrem canvis modestos en la microbiota intestinal, concloent que els efectes no estan mediats de manera significativa per la microbiota.
En el Segon Capítol avaluem el potencial anti-obesogènic i el mecanisme d'acció d'un nou bacteri Phascolarctobacterium faecium DSM 32890. Hem realitzat experiments in vitro i in vivo utilitzant diferents cultius cel·lulars (macròfags derivats de medul·la òssia i de cèl·lules limfoides innates intestinals del grup 1 (LC1s) i models murins d'obesitat induïda per la dieta (ratolins C57BL/6J, i Rag1-/- ). El tractament de ratolins alimentats amb una dieta hipercalòrica amb P. faecium incrementà la proporció dels macròfags M2 a l'intestí, contrarestant l'augment d'ILC1s i en última instància, mitigà la intolerància a la glucosa i l'augment del pes corporal, independentment de la viabilitat del bacteri. A més, P. faecium reforçà la funció bacterial intestinal i evità la inflamació sistèmica causada per la dieta hipercalòrica. Aquests beneficis metabòlics es mantenien en absència d'immunitat adaptativa, però es perderen quan el bacteri es coadministrà amb un inhibidor (GW2580) de la polarització de macròfags M2. Finalment, realitzàrem un ampli estudi amb dades metagenòmiques de 6.361 persones que mostrà una relació inversa entre P. faecium i l'obesitat, independentment de la nacionalitat, el sexe o l'edat, suggerint l'associació d'aquest bacteri amb la salut metabòlica.
En el Tercer Capítol, investiguem la implicació de les ILC1s residents en l'intestí en la progressió de l'obesitat i les alteracions metabòliques associades. Evaluàrem longitudinalment la resposta de les ILC1s i les conseqüències de la depleció de ILC1s en un model murí d'obesitat. A l'intestí, el bloqueig de ILC1s va evitar l'augment de macròfags M1 i ILC2s, i va promoure l'activació de la via ILC3-IL22, augmentant la producció de mucina, l'expressió de pèptids antimicrobians i el nombre de cèl·lules neuroendocrines. El bloqueig de ILC1s va restablir la microbiota i el seu metaboloma, similar a l'estat saludable. Aquestes millores es van associar amb una major secreció d'hormones intestinals, i una reducció de la insulinèmia i l'adipositat. / [EN] Obesity is a major public health challenge due to its high prevalence, and association with metabolic comorbidities. Hypercaloric diets are known to overactivate the intestinal immune system and disrupt the microbiome, ultimately causing detrimental metabolic effects. The loss of intestinal immune homeostasis is considered an early step preceding the development of systemic low-grade inflammation associated with obesity and metabolic complications. In this regard, extensive evidence supports that the gut microbiome may be modified favorable and, thus, help to ameliorate these conditions. Hence, identifying factors triggering the low-grade inflammation and microbiome-base solutions to reduce the obesity burden represent promising avenues of research.
This Doctoral Thesis aims to advance the knowledge and provide novel probiotics and dietary strategies to combat the burden of obesity based on their immunomodulatory properties to shape the metabolic response to the diet.
In the First Chapter, we have investigated the anti-obesogenic potential of propyl propane thiosulfinate (PTS), an organo-sulfur compound derived from Allium species, at two different doses (0.1 or 1 mg/kg/day) using a murine model of diet-induced obesity (DIO). Our preclinical findings showed the protective effects of PTS against obesity, reducing body weight gain and maintaining glucose homeostasis, thus suggesting its potential to ameliorate the impact of the HFHSD. In the adipose tissue and the liver, PTS reduced inflammation and the aberrant lipid metabolism caused by the obesogenic diet. Additionally, PTS promoted thermogenic activity in the brown adipose tissue and enhance intestinal gut barrier defense. In view of the modest changes in the microbial ecosystem, we concluded that the effects of PTS were not mediated by the gut microbiota.
In the Second Chapter, we have evaluated the anti-obesogenic potential and the mechanism of action of the new intestinal strain, Phascolarctobacterium faecium DSM 32890, isolated in our laboratory from a healthy volunteer. To that aim, we have performed different in vitro and in vivo experiments, including the use of different types of cell cultures (bone marrow-derived macrophages and group 1 of innate lymphoid cells (ILC1s)) and DIO murine models (wild-type C57BL/6J and Rag1-/- mice). Treatment of HFHSD-fed mice with P. faecium, regardless of its viability, shifted the macrophage phenotype towards an M2-type, which counteracted the obesity-induced increase in gut-resident ILC1s and ultimately mitigated glucose intolerance and body weight gain. Moreover, P. faecium treatment prevented systemic inflammation, boosted secretory immunoglobulin A production and induced antimicrobial peptide and interleukin 22 expression. These metabolic benefits were maintained in the absence of an adaptive immune system but were lost when the bacterium was co-administered with an inhibitor (GW2580) of M2 macrophage polarization. We confirmed that P. faecium was more prevalent in the gut metagenomes of non-obese adults regardless of nationality, sex or age, suggesting that it might contribute to safeguard metabolic health in humans.
In the Third Chapter, we have investigated the involvement of gut-resident ILC1s in obesity progression and metabolic disruption. To address this goal, we evaluated longitudinally, in a DIO murine model, the ILC1s response to an obesogenic diet and the consequences of the ILC1s depletion. In the intestine, ILC1s depletion blunted the increases in M1 macrophages and ILC2s. Additionally, ILC1s depletion promoted the ILC3-IL22 pathway, increasing mucin production, the expression of antimicrobial gut peptides, and the number of neuroendocrine cells. Moreover, ILC1s depletion restored microbial and metabolomic profiles, resembling those associated with a healthy symbiotic state. The improvements in gut homeostasis were linked to a higher gut hormone secretion, and reduced insulinemia and adiposity. / Rebeca Liébana García has been beneficiary of an FPU contract (FPU 18/02026)
and a mobility grant (EST22/00430) from Spanish Ministry of Universities.
The experimental work conduced in this Doctoral Thesis has been funded by the
Spanish Ministry of Science and Innovation (MICINN AGL2017-88801-P,
PID2020-119536RB-I00), the Centre for the Development of Industrial
Technology (CDTI, Ref 20170847), and the EU H2020 Marie Sklodowska Curie
Actions (MSCA-IF “MicroILCs, GA: 8905454). / Liébana García, R. (2023). Effect and Mechanisms of Action of Intestinal Bacteria and Bioactive Compounds on the Immune System and Metabolism in Obesity Models [Tesis doctoral]. Universitat Politècnica de València. https://doi.org/10.4995/Thesis/10251/201910 / Compendio
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