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Efectos hiperlipidémicos de las grasas saturadas de la dieta mediados por la coactivación PGC-1beta del SREBP
Jiandie Lin1, Ruojing Yang, Paul T Tarr
1Dana-Farber Cancer Institute and Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA.
Cell
|February 1, 2005
Resumen
Las dietas altas en grasas aumentan la expresión hepática de PGC-1beta y SREBP, promoviendo la hiperlipidemia. PGC-1beta reduce la grasa hepática pero aumenta los lípidos en la sangre, lo que contribuye a la atherogénesis.
Área de la Ciencia:
- Metabolismo y biología molecular.
- Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular Investigación Cardiovascular
Sus antecedentes:
- Los coactivadores de PGC-1 regulan los factores de transcripción y los receptores nucleares.
- Las proteínas de unión al elemento sensible al esterol (SREBPs) controlan los genes lipogénicos en el hígado.
Objetivo del estudio:
- Para investigar el papel de la PGC-1beta en la hiperlipidemia inducida por la dieta alta en grasas y la aterogénesis.
- Para aclarar el mecanismo por el cual PGC-1beta influye en el metabolismo de los lípidos hepáticos y el transporte de lipoproteínas.
Principales métodos:
- Análisis de la expresión génica (PGC-1beta, SREBP1c, SREBP1a) en el hígado después de una alimentación rica en grasas.
- Evaluación de la coactivación de SREBP por PGC-1beta y su papel en la expresión génica lipogénica.
- Evaluación del efecto de PGC-1beta en la acumulación de grasa hepática y los niveles de lípidos circulantes.
- Investigación de la interacción de PGC-1beta con el alfa del receptor X del hígado (LXRalpha).
Principales resultados:
- La alimentación con alto contenido de grasa aumentó la regulación de PGC-1beta y SREBP1c/1a en el hígado.
- PGC-1beta coactivó SREBPs, estimulando la expresión génica lipogénica y fue esencial para los efectos mediados por SREBP.
- PGC-1beta disminuyó la acumulación de grasa hepática pero aumentó los triglicéridos circulantes y el colesterol VLDL.
- PGC-1beta coactivó LXRalpha, mejorando el transporte de lipoproteínas.
Conclusiones:
- PGC-1beta juega un doble papel en el metabolismo de los lípidos hepáticos, reduciendo la grasa hepática y promoviendo la hiperlipidemia.
- Las grasas saturadas de la dieta pueden inducir hiperlipidemia y aterogénesis a través de la activación de PGC-1beta y SREBP.
- La coactivación de LXRalpha por PGC-1beta contribuye a alterar el metabolismo de las lipoproteínas.
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