Tuesday, 16 January 2024 16:03

Un estudio liderado por el CNB-CSIC identifica una proteína esencial en la regulación de la obesidad

Imagen en la que se observan diferencias en el desarrollo de los adipocitos (fluorescencia verde) en tejido adiposo procedente de un ratón sano o con mutaciones en la proteína Dido. Imagen en la que se observan diferencias en el desarrollo de los adipocitos (fluorescencia verde) en tejido adiposo procedente de un ratón sano o con mutaciones en la proteína Dido. María Ángeles García - CNB-CSIC
  • La proteína Dido1, conocida por su papel en la diferenciación de las células madre, tiene una función clave en el desarrollo del tejido adiposo
  • Este hallazgo abre nuevas vías de investigación y desarrollo de terapias dirigidas a la obesidad

La obesidad es una patología que afecta a más de mil millones de personas en el mundo y está considerada por la Organización Mundial de la Salud como una prioridad en el ámbito de la salud pública. Además, constituye un factor de riesgo para diferentes enfermedades lo que supone limitaciones en la expectativa y calidad de vida de las personas afectadas. Identificar los factores moleculares implicados es esencial de cara al desarrollo de terapias que permitan su regulación y control. Un estudio liderado por el Consejo Superior de Investigaciones Científicas (CSIC) ha descubierto que la proteína Dido1 es clave en el desarrollo del tejido adiposo y tiene capacidad de prevenir la obesidad incluso en situaciones de alimentación con dietas enriquecidas en grasas. El trabajo, que describe las funciones de Dido1 en el desarrollo del tejido adiposo, se publica en la revista Proceedings of the National Academy of Sciences (PNAS).

Mediante la generación de ratones genéticamente modificados, los autores identifican la capacidad de este gen para prevenir la obesidad. Thierry Fischer, investigador del CSIC en el Centro Nacional de Biotecnología (CNB-CSIC), da las claves del estudio. “El foco de nuestro laboratorio -señala- es el desarrollo de células madre y en los trabajos previos sobre la función de Dido1 habíamos observado que los ratones con mutaciones en el extremo amino terminal de la proteína presentaban un fenotipo diferencial: eran más delgados que los ratones silvestres”. “Por este motivo decidimos comprobar cuales eran las diferencias en su metabolismo”, continua Fischer.

El tejido adiposo es el principal órgano de almacenamiento de grasa y desempeña un papel fundamental en la regulación del metabolismo sistémico y en las enfermedades relacionadas con la obesidad. “Un tejido adiposo disfuncional puede inducir un exceso o una reducción de la grasa corporal (también llamada lipodistrofia). En este estudio, identificamos que la delgadez de los ratones mutantes se debe a una disminución del tejido adiposo y baja presencia de lípidos en sangre, incluso cuando sus condiciones de alimentación incluyen una dieta rica en grasas”, explica el investigador del CSIC.

Además, Gema Medina-Gómez, científica de la Universidad Rey Juan Carlos comenta: Hemos visto que cuando se realizan estudios del gasto energético e ingesta de los animales en jaulas metabólicas, los ratones mutados tienen más dificultades para utilizar los lípidos de la dieta de forma eficiente. Prefieren utilizar hidratos de carbono”. Otro de los interesantes hallazgos del estudio para Guadalupe Sabio, investigadora del Centro Nacional de Investigaciones Cardiovasculares (CNIC) es que “la alteración de la grasa, además de provocar delgadez, resulta en una ligera hipotermia en estos animales”.

Estos resultados, si bien se han obtenido en ratones experimentales, pueden tener importantes implicaciones terapéuticas en patologías metabólicas. Este modelo difiere de otros modelos de ratones lipodistróficos previamente publicados y podría constituir un nuevo sistema para la investigación y desarrollo de intervenciones terapéuticas dirigidas. “El desarrollo de este modelo puede ser muy útil para entender mejor la regulación del almacenamiento y la distribución de la grasa", explica María Ángeles García-López, también investigadora del CNB-CSIC y primera autora de la investigación.

La obtención de estos datos se ha logrado mediante la combinación de diferentes tecnologías punteras, y la colaboración con los grupos de investigación de Guadalupe Sabio en el Centro Nacional de Investigaciones Cardiovasculares y de Gema Medina-Gómez en la Universidad Rey Juan Carlos de Alcorcón.

Más información

María Ángeles García-López, Alfonso Mora, Patricia Corrales, Tirso Pons, Ainhoa, Sánchez de Diego, Amaia Talavera Gutiérrez, Karel H. M. van Wely, Gema Medina-Gómez, Guadalupe Sabio, Carlos Martínez-A, Thierry Fischer. DIDO is necessary for the adipogenesis that promotes diet-induced obesity. Proceedings of the National Academy of Sciences (PNAS)DOI: 10.1073/pnas.230009612

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