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El alto nivel de fructosa en los primeros años de vida afecta a la fagocitosis microglial y al desarrollo neurológico
Zhaoquan Wang1,2, Allie Lipshutz1, Celia Martínez de la Torre3,4
1Immunology Program, Sloan Kettering Institute, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|June 11, 2025
Resumen
El alto consumo de fructosa perjudica la fagocitosis microglial, crucial para el desarrollo del cerebro. El bloqueo de la absorción de fructosa a través de GLUT5 en la microglía previene esta disfunción y rescata comportamientos similares a la ansiedad en ratones adolescentes.
Área de la Ciencia:
- La neurociencia
- Biología del desarrollo
- Investigación metabólica
Sus antecedentes:
- El alto consumo de fructosa está relacionado con problemas de desarrollo neurológico.
- La fagocitosis microglial es esencial para el correcto desarrollo del cerebro.
- Se desconoce el impacto de la exposición temprana a la fructosa en la función microglial.
Objetivo del estudio:
- Investigar cómo el alto consumo de fructosa afecta a la fagocitosis microglial en los primeros años de vida.
- Determinar el papel del transportador de fructosa GLUT5 en la mediación de estos efectos.
- Explorar el vínculo mecánico entre la fructosa, la función microglial y la ansiedad adolescente.
Principales métodos:
- Los ratones fueron alimentados con dietas altas en fructosa durante el embarazo y neonatalmente.
- Se evaluó la actividad fagocítica microglial in vivo e in vitro.
- Se realizó una deleción genética de GLUT5 en la microglía neonatal.
- Se analizaron las vías metabólicas y la localización de la enzima (hexokinasa 2).
- Se evaluaron comportamientos similares a la ansiedad en la descendencia adolescente.
Principales resultados:
- La alta exposición a la fructosa disminuyó la actividad fagocítica microglial en ratones neonatales.
- La eliminación de GLUT5 en la microglía normalizó la función fagocítica.
- El alto contenido de fructosa aumentó la absorción de fructosa dependiente de GLUT5 y alteró el metabolismo microglial.
- Los ratones expuestos a altos niveles de fructosa mostraron comportamientos similares a la ansiedad, que fueron rescatados en ratones con deficiencia de GLUT5.
Conclusiones:
- El alto contenido de fructosa afecta directamente la fagocitosis microglial neonatal a través de la absorción mediada por GLUT5.
- El metabolismo microglial alterado contribuye a la disfunción fagocítica.
- La exposición temprana a la fructosa puede conducir a la ansiedad adolescente, mediada por GLUT5 y la función microglial.
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