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Identificación de un receptor nuclear para los ácidos biliares

M Makishima¹, A Y Okamoto, J J Repa

¹Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235-9050, USA.

Science (New York, N.Y.)

|May 21, 1999

Resumen

Los ácidos biliares son ligandos fisiológicos para el receptor farnesoide X (FXR). Los ácidos biliares controlan su propia síntesis y transporte mediante la regulación de la transcripción génica a través de la FXR.

Área de la Ciencia:

La bioquímica es la bioquímica.
Biología Molecular Biología Molecular
Endocrinología Endocrinología.

Sus antecedentes:

Los ácidos biliares son cruciales para la digestión y absorción de los lípidos de la dieta.
Son los principales productos finales de la descomposición del colesterol en el cuerpo.
Comprender la regulación de los ácidos biliares es clave para la salud metabólica.

Objetivo del estudio:

Para identificar los ligandos fisiológicos para el receptor nuclear huérfano FXR.
Para aclarar el mecanismo regulador de la síntesis y el transporte de ácido biliar.

Principales métodos:

Investigó la interacción entre los ácidos biliares y FXR.
Analizó los efectos transcripcionales de la activación de FXR en los genes objetivo.
Utilizó el análisis de la expresión génica para evaluar los impactos regulatorios.

Principales resultados:

Los ácidos biliares fueron identificados como ligandos naturales para FXR.
La activación de la FXR por los ácidos biliares reprimió el gen para el colesterol 7alfa-hidroxilasa, una enzima clave en la síntesis de ácidos biliares.
La activación de la FXR regulaba al alza el gen de la proteína de unión de ácido biliar intestinal, un transportador.

Conclusiones:

Los ácidos biliares actúan como moléculas de señalización que regulan sus propias vías metabólicas.
FXR es un mediador central en el control transcripcional de la homeostasis del ácido biliar.
Este descubrimiento revela un mecanismo de retroalimentación para la biosíntesis de ácidos biliares y la circulación enterohepática.

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