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La acumulación de succinato controla la activación de la termogénesis del tejido adiposo
Evanna L Mills1,2, Kerry A Pierce3, Mark P Jedrychowski1,2
1Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
Nature
|July 20, 2018
Resumen
La acumulación de succinato en el tejido adiposo desencadena la termogénesis independientemente de las vías tradicionales. Este descubrimiento revela un nuevo método para combatir la obesidad y mejorar la salud metabólica.
Área de la Ciencia:
- Las vías metabólicas
- Biología del tejido adiposo
- Termogénesis
Sus antecedentes:
- La termogénesis del tejido adiposo marrón y beige combate la enfermedad metabólica.
- La señalización adrenérgica a través de la AMP-proteína quinasa A cíclica inicia la termogénesis.
- Esta vía ha sido un foco de investigación clínica.
Objetivo del estudio:
- Identificar nuevas vías metabólicas que controlan la termogénesis del tejido adiposo.
- Investigar el papel del succinato en la termogénesis.
- Explorar el succinato como objetivo terapéutico para los trastornos metabólicos.
Principales métodos:
- Enfoque metabolómico comparado.
- Estudios in vivo en ratones.
- Análisis de la producción de especies reactivas de oxígeno y termogénesis dependiente de la UCP1.
Principales resultados:
- La acumulación de succinato es una firma de la termogénesis del tejido adiposo.
- El succinato activa la respiración termogénica independientemente de la señalización adrenérgica.
- La administración sistémica de succinato inicia la termogénesis y protege contra la obesidad.
- La oxidación del succinato a través de la succinato deshidrogenasa es crucial para la termogénesis.
Conclusiones:
- El succinato es un regulador metabólico independiente de la termogénesis del tejido adiposo.
- El succinato actúa como una molécula termogénica derivada sistémicamente.
- La elevación farmacológica del succinato ofrece una estrategia potencial para tratar la obesidad y la disfunción metabólica.
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