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Una señal del cerebro al intestino controla la absorción de grasa intestinal
Qianqian Lyu1,2, Wenzhi Xue1,3, Ruixin Liu1,2
1Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine (SJTUSM), Shanghai, China.
Nature
|September 11, 2024
Resumen
El cerebro
Área de la Ciencia:
- La neurociencia
- Gastroenterología
- Farmacología
Sus antecedentes:
- La grasa de la dieta es esencial para la energía, pero el exceso de ingesta causa obesidad.
- Se cree que la absorción de grasa intestinal se produce principalmente por difusión.
- El papel del eje cerebro-intestino en la absorción de grasa no se entiende bien.
Objetivo del estudio:
- Investigar el papel del núcleo motor dorsal del vago (DMV) en la regulación de la absorción de grasa intestinal.
- Identificar los mecanismos por los que el DMV influye en la absorción de grasa.
- Explorar el potencial terapéutico de dirigirse a la vía DMV-vagus para el control de peso.
Principales métodos:
- Inactivación y activación de las neuronas DMV en modelos animales.
- Análisis de la longitud de las microvillas jejunales y de la absorción de grasa.
- Identificación y análisis estructural de la unión de la puerarina a los receptores GABAA utilizando el etiquetado de fotoafinidad y la microscopía criolectrónica.
- El golpe condicional de Gabra1 en el DMV.
Principales resultados:
- La inactivación de la neurona DMV redujo la absorción de grasa intestinal y causó pérdida de peso.
- La activación de las neuronas DMV aumentó la absorción de grasa y el aumento de peso.
- Dirigirse a las neuronas DMV específicas que se proyectan hacia el yeyuno acortó los microvilli, disminuyendo la absorción de grasa.
- El compuesto natural puerarina suprimió la vía DMV-vagus, reduciendo la absorción de grasa.
- La puerarina se une a un sitio alostérico en los receptores GABA A.
- El nocaut condicional de Gabra1 en el DMV bloqueó en gran medida el efecto de la puerarina en la absorción de grasa.
Conclusiones:
- El núcleo motor dorsal del vago (DMV) es un regulador clave de la absorción de grasa intestinal a través del eje cerebro-intestino.
- La supresión del eje DMV-vagus-jejunum reduce la absorción de grasa al acortar las microvillas.
- La puerarina, que actúa a través de los receptores GABAA en el DMV, ofrece una estrategia terapéutica potencial para controlar la absorción de grasa y promover la pérdida de peso.
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