STUDY OF THE EFFECT OF QUERCETIN TREATMENT AND INTESTINAL MICROBIOTA TRANSPLANTATION ON EXPERIMENTAL MODELS OF NON-ALCOHOLIC FATTY LIVER (Q3167632): Difference between revisions
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(Created claim: summary (P836): NON-ALCOHOLIC LIVER DISEASE (NAFLD) INCLUDES FROM STEATOSIS TO NON-ALCOHOLIC STEATOHEPATITIS (NASH), CIRRHOSIS AND HEPATOCARCINOMA, AND IS RELATED TO OBESITY, INSULIN RESISTANCE AND TYPE 2 DIABETES MELLITUS, AMONG OTHER METABOLIC DISORDERS. IN DISEASE PATHOGENESIS INSULIN RESISTANCE INDUCES LIPID ACCUMULATION IN HEPATOCYTES AND THE DEVELOPMENT OF OXIDATIVE STRESS, WHICH TRIGGERS THE RELEASE OF PRO-INFLAMMATORY CYTOKINES. THE INTRACITOPLASMATIC A...) |
(Changed label, description and/or aliases in en: translated_label) |
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STUDY OF THE EFFECT OF QUERCETIN TREATMENT AND INTESTINAL MICROBIOTA TRANSPLANTATION ON EXPERIMENTAL MODELS OF NON-ALCOHOLIC FATTY LIVER | |||
Revision as of 17:32, 12 October 2021
Project Q3167632 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | STUDY OF THE EFFECT OF QUERCETIN TREATMENT AND INTESTINAL MICROBIOTA TRANSPLANTATION ON EXPERIMENTAL MODELS OF NON-ALCOHOLIC FATTY LIVER |
Project Q3167632 in Spain |
Statements
53,240.0 Euro
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106,480.0 Euro
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50.0 percent
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1 January 2014
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31 December 2016
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UNIVERSIDAD DE LEON
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42°38'2.94"N, 5°58'17.11"W
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24089
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LA ENFERMEDAD DEL HIGADO GRASO NO ALCOHOLICO (NAFLD) INCLUYE DESDE ESTEATOSIS A ESTEATOHEPATITIS NO ALCOHOLICA (NASH), CIRROSIS Y HEPATOCARCINOMA, Y SE RELACIONA CON OBESIDAD, RESISTENCIA A LA INSULINA Y DIABETES MELLITUS TIPO 2, ENTRE OTRAS ALTERACIONES METABOLICAS. EN LA PATOGENESIS DE LA ENFERMEDAD LA RESISTENCIA A LA INSULINA INDUCE EL ACUMULO LIPIDICO EN LOS HEPATOCITOS Y EL DESARROLLO DE ESTRES OXIDATIVO, LO QUE ACTIVA LA LIBERACION DE CITOQUINAS PROINFLAMATORIAS. EL ACUMULO INTRACITOPLASMATICO DE LIPIDOS SE ASOCIA A UNA ALTERACION DEL METABOLISMO LIPIDICO DEPENDIENTE DE FACTORES DE TRANSCRIPCION TALES COMO EL RECEPTOR NUCLEAR X DEL HIGADO (LXR)ALFA. ESTAN DESCRITOS LOS POSIBLES EFECTOS BENEFICIOSOS DE LOS FLAVONOIDES, INCLUYENDO LA QUERCITINA, SOBRE EL DESARROLLO Y EVOLUCION DE LA NAFLD, DADA SU CAPACIDAD ANTIOXIDANTE, ANTIINFLAMATORIA Y DE MODULAR EL METABOLISMO LIPOGENICO, LO CUAL LES CONFIERE UN GRAN POTENCIAL TERAPEUTICO. NO OBSTANTE, NO EXISTE INFORMACION SOBRE EL EFECTO DE LA QUERCETINA SOBRE LA EXPRESION DEL FACTOR NUCLEAR LXRALFA NI EN CONDICIONES BASALES NI EN MODELOS IN VIVO E IN VITRO DE NAFLD. POR OTRA PARTE, EXISTEN NUMEROSAS EVIDENCIAS QUE IDENTIFICAN A LA MICROBIOTA INTESTINAL COMO UN FACTOR CLAVE EN EL DESARROLLO DE OBESIDAD, SINDROME METABOLICO E HIGADO GRASO NO ALCOHOLICO. DE HECHO, LA ENFERMEDAD DE HIGADO GRASO NO ALCOHOLICO Y SU EVOLUCION A NASH SE ASOCIAN CON UNA DISBIOSIS Y UN INCREMENTO DE LA PERMEABILIDAD INTESTINAL. A ESTE RESPECTO, TANTO BACTERIAS COMO PRODUCTOS BACTERIANOS PARECEN INICIAR UNA RESPUESTA INMUNE E INFLAMATORIA, RESULTANDO DICHA ENDOTOXEMIA CRONICA EN UNA HEPATOTOXICIDAD CLAVE EN EL DESARROLLO DE LA NAFLD. DICHOS HALLAZGOS PLANTEAN LA POSIBLE UTILIDAD DE NUEVAS APROXIMACIONES TERAPEUTICAS BASADAS EN LA MODIFICACION DEL MICROBIOMA INTESTINAL. ASI, RECIENTEMENTE SE HA PROPUESTO LA UTILIDAD DEL TRASPLANTE DE MICROBIOTA INTESTINAL COMO MECANISMO TERAPEUTICO EN EL TRATAMIENTO DE LA NAFLD. ADEMAS, SE HA SUGERIDO LA CAPACIDAD DE LA QUERCETINA DE ACTUAR COMO AGENTE PREBIOTICO, SI BIEN NO EXISTE NINGUN ESTUDIO QUE LO CORROBORE EN MODELOS EXPERIMENTALES IN VIVO. POR ELLO, COMO OBJETIVO GENERAL DEL PROYECTO NOS PROPONEMOS ESTUDIAR LOS EFECTOS DEL TRATAMIENTO EXPERIMENTAL CON QUERCETINA Y DEL TRASPLANTE DE MICROBIOTA INTESTINAL PROCEDENTE DE RATONES TRAS LA INDUCCION DE ENFERMEDAD DE HIGADO GRASO NO ALCOHOLICO (DIETA RICA EN GRASA, HFD) EN PRESENCIA O AUSENCIA DE QUERCETINA, A RATONES LIBRES DE GERMENES A LOS QUE SE LES SOMETERA A SU VEZ AL MISMO PROTOCOLO DE INDUCCION DE NAFLD Y TRATAMIENTO CON EL FLAVONOL. SE ESTUDIARA EL EFECTO DEL TRATAMIENTO CON QUERCETINA Y DEL TRASPLANTE DE MICROBIOTA Y DE LA COMBINACION DE DICHOS TRATAMIENTOS SOBRE EL PESO CORPORAL E INDICADORES EXTRAHEPATICOS DEL SINDROME METABOLICO, LA COMPOSICION DE LA MICROBIOTA INTESTINAL, ASI COMO DE LOS MECANISMOS PATOGENICOS A NIVEL HEPATICO QUE INVOLUCRAN FUNDAMENTALMENTE AL ESTRES OXIDATIVO, LA INFLAMACION, EL DESARROLLO DE ESTRES DEL RETICULO ENDOPLASMICO Y LAS VIAS DE SEÑALIZACION CELULAR RELACIONADAS CON LA ALTERACION DEL METABOLISMO LIPIDICO DEPENDIENTE DE LXRALFA EN NUESTROS MODELOS EXPERIMENTALES IN VIVO E IN VITRO DE NAFLD. EL ESTUDIO INTENTARA PROFUNDIZAR EN EL POTENCIAL PAPEL DE LA ADMINISTRACION DE FLAVONOIDES COMO ANTIOXIDANTES NATURALES CON POSIBLE CAPACIDAD PREBIOTICA Y DEL TRASPLANTE DE MICROBIOTA INTESTINAL EN EL MANEJO DE LA ENFERMEDAD DE HIGADO GRASO NO ALCOHOLICO. (Spanish)
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NON-ALCOHOLIC LIVER DISEASE (NAFLD) INCLUDES FROM STEATOSIS TO NON-ALCOHOLIC STEATOHEPATITIS (NASH), CIRRHOSIS AND HEPATOCARCINOMA, AND IS RELATED TO OBESITY, INSULIN RESISTANCE AND TYPE 2 DIABETES MELLITUS, AMONG OTHER METABOLIC DISORDERS. IN DISEASE PATHOGENESIS INSULIN RESISTANCE INDUCES LIPID ACCUMULATION IN HEPATOCYTES AND THE DEVELOPMENT OF OXIDATIVE STRESS, WHICH TRIGGERS THE RELEASE OF PRO-INFLAMMATORY CYTOKINES. THE INTRACITOPLASMATIC ACCUMULATION OF LIPIDS IS ASSOCIATED WITH AN ALTERATION OF LIPID METABOLISM DEPENDENT ON TRANSCRIPTION FACTORS SUCH AS THE NUCLEAR X LIVER RECEPTOR (LXR)ALPHA. THE POSSIBLE BENEFICIAL EFFECTS OF FLAVONOIDS, INCLUDING QUERCITHIN, ON THE DEVELOPMENT AND EVOLUTION OF NAFLD ARE DESCRIBED, GIVEN ITS ANTIOXIDANT, ANTI-INFLAMMATORY AND MODULATION CAPACITY OF LIPOGENICO METABOLISM, WHICH GIVES THEM GREAT THERAPEUTIC POTENTIAL. HOWEVER, THERE IS NO INFORMATION ON THE EFFECT OF QUERCETIN ON THE EXPRESSION OF THE NUCLEAR FACTOR LXRALFA UNDER BASELINE CONDITIONS OR IN VIVO AND IN VITRO MODELS OF NAFLD. ON THE OTHER HAND, THERE IS NUMEROUS EVIDENCE THAT IDENTIFIES THE INTESTINAL MICROBIOTA AS A KEY FACTOR IN THE DEVELOPMENT OF OBESITY, METABOLIC SYNDROME AND NON-ALCOHOLIC FATTY LIVER. IN FACT, NON-ALCOHOLIC LIVER DISEASE AND ITS EVOLUTION TO NASH ARE ASSOCIATED WITH DYSBIOSIS AND INCREASED INTESTINAL PERMEABILITY. IN THIS RESPECT, BOTH BACTERIA AND BACTERIAL PRODUCTS APPEAR TO INITIATE AN IMMUNE AND INFLAMMATORY RESPONSE, RESULTING IN THIS CHRONIC ENDOTOXAEMIA IN A KEY HEPATOTOXICITY IN THE DEVELOPMENT OF NAFLD. THESE FINDINGS RAISE THE POSSIBLE USEFULNESS OF NEW THERAPEUTIC APPROACHES BASED ON THE MODIFICATION OF THE INTESTINAL MICROBIOME. THUS, RECENTLY IT HAS BEEN PROPOSED THE USEFULNESS OF INTESTINAL MICROBIOTA TRANSPLANTATION AS A THERAPEUTIC MECHANISM IN THE TREATMENT OF NAFLD. IN ADDITION, THE ABILITY OF QUERCETIN TO ACT AS A PREBIOTIC AGENT HAS BEEN SUGGESTED, ALTHOUGH THERE IS NO STUDY TO CORROBORATE IT IN EXPERIMENTAL MODELS IN VIVO. FOR THIS REASON, AS A GENERAL OBJECTIVE OF THE PROJECT WE PROPOSE TO STUDY THE EFFECTS OF THE EXPERIMENTAL TREATMENT WITH QUERCETIN AND THE TRANSPLANTATION OF INTESTINAL MICROBIOTA FROM MICE FOLLOWING THE INDUCTION OF NON-ALCOHOLIC FATTY LIVER DISEASE (RICH DIET IN FAT, HFD) IN THE PRESENCE OR ABSENCE OF QUERCETIN, TO MICE FREE OF GERMS TO WHICH IN TURN WERE SUBJECTED TO THE SAME PROTOCOL OF NAFLD INDUCTION AND TREATMENT WITH FLAVONOL. WE WILL STUDY THE EFFECT OF QUERCETIN TREATMENT AND MICROBIOTA TRANSPLANTATION AND THE COMBINATION OF THESE TREATMENTS ON BODY WEIGHT AND EXTRAHEPATIC INDICATORS OF METABOLIC SYNDROME, THE COMPOSITION OF THE INTESTINAL MICROBIOTA, AS WELL AS THE HEPATIC PATOGENICAL MECHANISMS THAT MAINLY INVOLVE OXIDATIVE STRESS, INFLAMMATION, THE DEVELOPMENT OF STRESS FROM ENDOPLASMICO RETICULUM AND CELLULAR SIGNALING PATHWAYS RELATED TO THE ALTERATION OF LIPID METABOLISM DEPENDENT ON LXRALFA IN OUR IN VIVO AND IN VITRO NAFLD EXPERIMENTAL MODELS. THE STUDY WILL ATTEMPT TO DEEPEN THE POTENTIAL ROLE OF THE ADMINISTRATION OF FLAVONOIDS AS NATURAL ANTIOXIDANTS WITH POSSIBLE PREBIOTICA CAPACITY AND OF INTESTINAL MICROBIOTA TRANSPLANTATION IN THE MANAGEMENT OF NON-ALCOHOLIC FATTY LIVER DISEASE. (English)
12 October 2021
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León
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Identifiers
BFU2013-48141-R
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