Relevance of dihydroceramide desaturase activity in the progression of the fatty liver and its pharmacological modulation. (Q3150050): Difference between revisions
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(Created claim: summary (P836): The general objective is to investigate the relevance of the metabolism of ceramides, a group of lipid modulators of many cell processes, in the etiopathogeny of non-alcoholic fatty liver disease. In particular, we propose to investigate: 1) The effect of pharmacological modulation of the enzyme dihydroceramide desaturase-1 on the progression of the fatty liver (objective 1), 2) The participation of ceramide metabolism in the regulation of intra...) |
(Changed label, description and/or aliases in en: translated_label) |
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Relevance of dihydroceramide desaturase activity in the progression of the fatty liver and its pharmacological modulation. | |||
Revision as of 14:45, 12 October 2021
Project Q3150050 in Spain
| Language | Label | Description | Also known as |
|---|---|---|---|
| English | Relevance of dihydroceramide desaturase activity in the progression of the fatty liver and its pharmacological modulation. |
Project Q3150050 in Spain |
Statements
33,500.0 Euro
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67,000.0 Euro
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50.0 percent
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1 January 2019
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31 March 2022
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FUNDACION INVESTIGACION BIOMEDICA HOSPITAL RAMON Y CAJAL
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40°25'0.12"N, 3°42'12.89"W
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28079
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El objetivo general es investigar la relevancia del metabolismo de las ceramidas, un grupo de lípidos moduladores de muchos procesos celulares, en la etiopatogenia de la enfermedad por hígado graso no alcohólico. En concreto, proponemos investigar: 1) El efecto de la modulación farmacológica de la enzima dihidroceramida desaturasa-1 en la progresión del hígado graso (objetivo 1), 2) La participación del metabolismo de ceramidas en la regulación de los depósitos intracelulares de lípidos y el efecto de la actividad desaturasa (objetivo 2) y 3) La patocronía de las alteraciones del metabolismo de ceramidas y su relación con los estadios y progresión de la enfermedad (objetivos 1 y 3). Nuestro diseño combina modelos experimentales animales y células en cultivo (objetivos 1 y 2) con estudios en pacientes con hígado graso (objetivo 3). El abordaje metodológico comprende la realización de estudios lipidómicos, el empleo de trazadores metabólicos para el seguimiento de intermediarios de la síntesis de ceramidas, estudios histológicos e inmunocitoquímicos para caracterizar el depósito de lípidos y la fibrogénesis en células y tejidos, el aislamiento de subfracciones celulares y extracelulares para estudiar los su composición, la realización de diversos marcadores proteicos por western-blot y el estudio de la expresión de las enzimas implicadas en la regulación del metabolismo de ceramidas y otros lípidos. De comprobarse la hipótesis, la utilización de inhibidores del metabolismo de las ceramidas abrirá nuevas posibilidades de tratamiento de esta enfermedad. (Spanish)
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The general objective is to investigate the relevance of the metabolism of ceramides, a group of lipid modulators of many cell processes, in the etiopathogeny of non-alcoholic fatty liver disease. In particular, we propose to investigate: 1) The effect of pharmacological modulation of the enzyme dihydroceramide desaturase-1 on the progression of the fatty liver (objective 1), 2) The participation of ceramide metabolism in the regulation of intracellular lipid deposits and the effect of desaturase activity (objectives 2) and (3) The pathochrony of alterations in ceramide metabolism and their relationship with stages and progression of the disease (objectives 1 and 3). Our design combines experimental animal models and cultured cells (Objectives 1 and 2) with studies in fatty liver patients (Objective 3). The methodological approach includes the performance of lipid studies, the use of metabolic tracers for the monitoring of ceramide synthesis intermediaries, histological and immunocytochemical studies to characterise lipid deposit and fibrogenesis in cells and tissues, the isolation of cell and extracellular subfractions to study their composition, the performance of various protein markers by western-blot and the study of the expression of enzymes involved in the regulation of ceramide and other lipid metabolism. If the hypothesis is tested, the use of ceramide metabolism inhibitors will open up new treatment possibilities for this disease. (English)
12 October 2021
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Madrid
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Identifiers
PI18_01152
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