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Sihao Liu¹, Jonathan D Brown, Kristopher J Stanya

¹1] Department of Genetics and Complex Diseases, Division of Biological Sciences, Harvard School of Public Health, 665 Huntington Avenue, Boston, Massachusetts 02115, USA [2].

|October 25, 2013

Resumen

Los investigadores descubrieron una nueva vía en la que el PPARδ del hígado controla el uso de grasa en los músculos a través de un lípido específico, PC ((18:0/18:1). Este hallazgo vincula la lipogénesis hepática con el uso de energía muscular y puede afectar a trastornos metabólicos como la obesidad.

Área de la Ciencia:

Regulación del metabolismo.
Los ritmos circadianos son el ritmo circadiano.
El metabolismo de los lípidos.

Sus antecedentes:

La lipogénesis hepática de novo convierte la glucosa en grasa, siguiendo ritmos circadianos y regulados por factores como Rev-erbα/β.
Las alteraciones en la lipogénesis hepática están vinculadas a problemas metabólicos sistémicos, lo que sugiere la comunicación entre órganos.

Objetivo del estudio:

Identificar los activadores transcripcionales de la síntesis rítmica de lípidos durante el ciclo oscuro.
Para aclarar el papel del hígado en la comunicación con los tejidos periféricos para la homeostasis energética.
Para definir una vía dependiente de PPARδ que vincula la lipogénesis hepática a la utilización de la grasa muscular.

Principales métodos:

Investigó el papel de PPARδ en la expresión génica lipogénica diurna en el hígado.
Se utilizaron modelos de activación de PPARδ específicos del hígado y de eliminación de hepatocitos-Ppard en ratones.
Se empleó un perfil de metabolito imparcial para identificar los lípidos circulantes clave.
PC administrado ((18:0/18:1) en modelos de ratón de obesidad inducida por la dieta y db/db.

Principales resultados:

PPARδ controla la expresión diurna de los genes lipogénicos hepáticos durante la alimentación.
La activación del PPARδ en el hígado aumenta la absorción de ácidos grasos musculares; su deleción la reduce.
Identificó la fosfatidilcolina 18:0/18:1 (PC(18:0/18:1)) como un lípido sérico regulado por el PPARδ hepático diurno.
PC(18:0/18:1) reduce los lípidos postprandiales y aumenta el uso de ácidos grasos musculares a través de PPARα.
La alimentación con alto contenido de grasa interrumpe la producción rítmica de PC ((18:0/18:1)); la administración mejora la homeostasis metabólica en ratones db/db.

Conclusiones:

Un eje de señalización PPARδ-PC(18:0/18:1) en el hígado regula la utilización de lípidos musculares.
Esta vía integra la síntesis de lípidos hepáticos con el gasto energético periférico.
La desregulación de esta señalización diurna puede contribuir a trastornos metabólicos como la obesidad.

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