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El metabolito microbiano intestinal inducido por la obesidad promueve el cáncer de hígado a través de la secretoma de
Shin Yoshimoto1, Tze Mun Loo, Koji Atarashi
1Division of Cancer Biology, Cancer Institute, Japanese Foundation for Cancer Research, Koto-ku, Tokyo 135-8550, Japan.
Nature
|June 28, 2013
Resumen
La obesidad promueve el cáncer de hígado a través de las bacterias intestinales que producen ácido desoxicólico (DCA), que desencadena el fenotipo secretor asociado a la senescencia (SASP) en las células hepáticas. El bloqueo de DCA o SASP previene el desarrollo de cáncer en ratones obesos.
Área de la Ciencia:
- Hepatología Hepatología.
- Oncología Oncología.
- Microbiología Microbiología.
Sus antecedentes:
- La obesidad es un creciente problema de salud mundial y un factor de riesgo significativo para varios tipos de cáncer, incluido el carcinoma hepatocelular (HCC).
- Los mecanismos moleculares precisos que vinculan la obesidad al desarrollo del cáncer siguen siendo incompletamente entendidos.
- Comprender estos mecanismos es crucial para desarrollar estrategias efectivas de prevención y tratamiento del cáncer.
Objetivo del estudio:
- Investigar el papel del fenotipo secretor asociado a la senescencia (SASP) en el desarrollo del carcinoma hepatocelular asociado a la obesidad (CCH).
- Para dilucidar las vías moleculares que conectan la obesidad, la microbiota intestinal y HCC.
- Identificar posibles objetivos terapéuticos para la prevención del CHC impulsado por la obesidad.
Principales métodos:
- Se utilizaron modelos de ratón de obesidad dietética y genética.
- Investigó el impacto de las alteraciones de la microbiota intestinal y los niveles de ácido desoxicólico (DCA).
- Evaluó el papel de las células esteladas hepáticas (HSC) y SASP en el desarrollo de HCC.
- Se examinaron tejidos humanos de HCC de pacientes con esteatohepatitis no alcohólica.
Principales resultados:
- La obesidad altera la microbiota intestinal, aumentando los niveles de ácido desoxicólico (DCA), que daña el ADN.
- El DCA desencadena SASP en las células estelares hepáticas (HSC), promoviendo el desarrollo de HCC en ratones obesos.
- El bloqueo de la producción de DCA o la reducción de las bacterias intestinales previene el HCC en ratones obesos.
- La inhibición de SASP o el agotamiento de las HSC senescentes también suprimió el desarrollo de HCC.
- SASP se observó en HSCs dentro de los tejidos humanos de HCC de pacientes con esteatohepatitis no alcohólica.
Conclusiones:
- El eje ácido desoxicólico (DCA) -SASP en las células esteladas hepáticas (HSC) juega un papel crítico en el desarrollo de HCC asociado a la obesidad.
- Dirigirse a la microbiota intestinal, DCA o SASP presenta una estrategia prometedora para controlar el cáncer de hígado impulsado por la obesidad.
- Los hallazgos sugieren una vía conservada que contribuye al HCC humano en el contexto de la obesidad y la esteatohepatitis no alcohólica.
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