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NCoR1 es un modulador fisiológico conservado de la masa muscular y la función oxidativa
Hiroyasu Yamamoto1, Evan G Williams, Laurent Mouchiroud
1Laboratory of Integrative and Systems Physiology, École Polytechnique Fédérale de Lausanne, CH-1015 Lausanne, Switzerland.
Cell
|November 15, 2011
Resumen
La pérdida del receptor nuclear corepressor 1 (NCoR1) mejora la resistencia al ejercicio al aumentar la masa muscular y la función mitocondrial. Esto sugiere que la interferencia de NCoR1 podría mejorar la fisiología y el rendimiento muscular.
Área de la Ciencia:
- Fisiología muscular La fisiología muscular.
- Reglamento de transcripción por escrito.
- La biogénesis mitocondrial es la biogénesis mitocondrial.
Sus antecedentes:
- Los correguladores de transcripción modulan la expresión génica mediante el control de la actividad del factor de transcripción.
- El corepresor 1 del receptor nuclear (NCoR1) es un coreregulador transcripcional clave.
- Comprender el papel de NCoR1 en el músculo es crucial para obtener información sobre el metabolismo y el rendimiento.
Objetivo del estudio:
- Para investigar el papel de NCoR1 en la fisiología muscular y el rendimiento del ejercicio.
- Para determinar los mecanismos moleculares subyacentes a los efectos de NCoR1 en el músculo.
- Explorar el potencial de dirigirse a NCoR1 para obtener beneficios terapéuticos.
Principales métodos:
- Se generaron ratones con pérdida de NCoR1 específica del músculo.
- Evaluación de la resistencia al ejercicio, la masa muscular y el contenido/actividad mitocondrial.
- Se analizó la activación de los principales factores de transcripción relacionados con el músculo (MEF2, PPARβ/δ, ERR).
- Se utilizaron modelos de *C. elegans* para estudiar la función del homólogo de NCoR (gei-8).
Principales resultados:
- La pérdida de NCoR1 específica del músculo mejoró significativamente la resistencia al ejercicio en ratones.
- La deficiencia de NCoR1 condujo a un aumento de la masa muscular y el número/actividad mitocondrial.
- La activación de MEF2, PPARβ/δ y ERRs se correlacionó con una mejor función muscular.
- Los niveles reducidos de NCoR1 promueven la oxidación de las grasas y aumentan el metabolismo oxidativo.
- La reducción del homólogo NCoR en *C. elegans* también aumentó la respiración mitocondrial.
Conclusiones:
- NCoR1 juega un papel adaptativo en la regulación de la fisiología muscular y el metabolismo energético.
- La deficiencia de NCoR1 mejora la capacidad oxidativa y el rendimiento del ejercicio.
- Dirigirse a NCoR1 presenta una estrategia potencial para mejorar la función muscular y la salud metabólica.
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