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Iniciación del cambio del mioblasto a la grasa marrón por un complejo transcripcional PRDM16-C/EBP-beta
Shingo Kajimura1, Patrick Seale, Kazuishi Kubota
1Dana-Farber Cancer Institute, Harvard Medical School, 44 Binney Street, Boston, Massachusetts 02115, USA.
Nature
|July 31, 2009
Resumen
PRDM16 y C/EBP-beta forman un complejo que cambia el destino celular, creando células de grasa marrón de los precursores. Este descubrimiento ofrece nuevas terapias potenciales para la obesidad y la diabetes tipo 2.
Área de la Ciencia:
- Biología celular Biología celular.
- El metabolismo es el metabolismo.
- Biología Molecular Biología Molecular
Sus antecedentes:
- Las células adiposas marrones disipan energía en forma de calor, combatiendo el resfriado y la obesidad.
- Se sabe que la proteína PRDM16 induce la determinación y diferenciación de la grasa marrón.
- Los mecanismos moleculares precisos que controlan el interruptor de desarrollo de la grasa marrón siguen sin estar claros.
Objetivo del estudio:
- Para dilucidar los mecanismos moleculares por los cuales PRDM16 controla el destino celular cambiar a la grasa marrón.
- Investigar el papel de PRDM16 en la formación de un complejo transcripcional para el desarrollo de la grasa marrón.
- Evaluar el potencial de PRDM16 y C/EBP-beta para inducir la formación de grasa marrón en las células no grasas.
Principales métodos:
- Investigó la interacción entre PRDM16 y C/EBP-beta.
- Expresión forzada utilizada de PRDM16 y C/EBP-beta en células fibroblásticas.
- Transplantó fibroblastos diseñados en ratones para formar almohadillas de grasa ectópica.
- Evaluación de la absorción de glucosa en el tejido graso marrón sintético mediante tomografía por emisión de positrones (PET) con fluorodeoxiglucosa (FDG).
Principales resultados:
- PRDM16 forma un complejo de transcripción con la forma activa de C/EBP-beta (LAP).
- Este complejo PRDM16-C/EBP-beta es crítico para cambiar el destino celular de los precursores mioblásticos a las células de grasa marrón.
- La expresión forzada de PRDM16 y C/EBP-beta indujo un programa funcional de grasa marrón en fibroblastos de ratón y humanos.
- Los fibroblastos trasplantados formaron tejido graso marrón ectópico que exhibió una absorción de glucosa similar a la grasa marrón endógena.
Conclusiones:
- El complejo PRDM16-C/EBP-beta inicia la formación de grasa marrón a partir de los precursores mioblásticos.
- Este mecanismo proporciona una nueva vía para la generación de grasa marrón.
- Los hallazgos sugieren posibles estrategias terapéuticas para la obesidad y la diabetes tipo 2 mediante la manipulación de este complejo.
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