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Mfsd2a es un transportador para el ácido graso esencial omega-3 ácido docosahexaenoico

Long N Nguyen¹, Dongliang Ma², Guanghou Shui³

¹Signature Research Program in Cardiovascular and Metabolic Disorders, Duke-NUS Graduate Medical School Singapore, 8 College Road, 169857 Singapore.

|May 16, 2014

Resumen

El dominio de la superfamilia principal de facilitadores que contiene la proteína 2a (Mfsd2a) se identifica como el transportador primario para la absorción de ácido docosahexaenoico (DHA) en el cerebro. Este descubrimiento revela el papel crucial de Mfsd2a en el desarrollo y la función del cerebro.

Área de la Ciencia:

La neurociencia es la neurociencia.
Biología Molecular Biología Molecular
La bioquímica es la bioquímica.

Sus antecedentes:

El ácido docosahexaenoico (DHA), un ácido graso omega-3, es vital para el crecimiento del cerebro y la función cognitiva.
El DHA está altamente concentrado en los fosfolípidos cerebrales, pero no puede sintetizarse de novo en el cerebro, lo que requiere transporte a través de la barrera hematoencefálica.
Los mecanismos que gobiernan la absorción de DHA en el cerebro han permanecido en gran parte desconocidos.

Objetivo del estudio:

Para identificar el transportador clave responsable de la absorción de ácido docosahexaenoico (DHA) en el cerebro.
Aclarar el mecanismo y la importancia fisiológica del transporte de DHA a través de la barrera hematoencefálica.

Principales métodos:

Identificación de Mfsd2a como un transportador potencial utilizando la bioinformática y el análisis de la expresión.
Generación y análisis de ratones Mfsd2a-knockout para evaluar los niveles de DHA y la función neurológica.
Ensayos in vitro basados en células para determinar el sustrato de transporte y el mecanismo de Mfsd2a.
Análisis lipidómico del tejido cerebral de ratones tipo salvaje y tipo knockout.

Principales resultados:

Mfsd2a fue identificado como el principal transportador para la absorción de DHA en el cerebro, expresado exclusivamente en el endotelio de la barrera hematoencefálica.
Los ratones Mfsd2a knockout exhibieron niveles significativamente reducidos de DHA en el cerebro, pérdida neuronal, déficits cognitivos y microcefalia.
Se encontró que Mfsd2a transporta DHA en forma de lisofosfatidilcolina (LPC), específicamente LPC con cadenas acilo de 14 carbonos o más, de una manera dependiente del sodio.
El grupo de cabeza fosforo-zwitteriónico de LPC fue crítico para el transporte mediado por Mfsd2a.

Conclusiones:

Mfsd2a es el transportador esencial que media la absorción de DHA ligado a la lisofosfatidilcolina en el cerebro.
Mfsd2a juega un papel crítico en el desarrollo del cerebro, la integridad neuronal y la función cognitiva.
Las lisofosfatidilcolinas derivadas del plasma son cruciales para el crecimiento y la función del cerebro, siendo Mfsd2a el mediador clave.

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