at the CNIC

Tag: obesity (Page 1 of 10)

JNK-mediated disruption of bile acid homeostasis promotes intrahepatic cholangiocarcinoma

Elisa Manieri, Cintia Folgueira, María Elena Rodríguez, Luis Leiva-Vega, Laura Esteban-Lafuente, Chaobo Chen, Francisco Javier Cubero, Tamera Barrett, Julie Cavanagh-Kyros, Davide Seruggia, Alejandro Rosell, Fátima Sanchez-Cabo, Manuel Jose Gómez, Maria J. Monte, Jose J. G. Marin, Roger J. Davis, Alfonso Mora & Guadalupe Sabio.

Obesity is associated with hepatic steatosis and activation of the cJun NH2-terminal kinase (JNK) stress-signaling pathway. Studies in mice demonstrate that JNK deficiency in the liver prevents the development of hepatic steatosis. This observation suggests that inhibition of JNK signaling may represent a possible treatment for hepatic steatosis. However, the long-term consequences of JNK inhibition are poorly understood.

Liver cholangiocarcinoma (Photo: Chaobo Chen).

Here we demonstrate that loss of JNK causes changes in cholesterol and bile acid metabolism that promote cholestasis, bile duct proliferation, and intrahepatic cholangiocarcinoma. We identify PPARα activation as the molecular mechanism that accounts for this phenotype .

Our analysis has important implications for the long-term use of JNK inhibitors for the treatment of obesity.

¿De qué mueren los extremeños?

«Aunque la supervivencia del cáncer ha aumentado hasta superar el 50% de forma global, la incidencia y la mortalidad siguen al alza por el envejecimiento de la población», explica Guadalupe Sabio, científica del Centro Nacional de Investigaciones Cardiovasculares Carlos III (CNIC), que incide también en que «los tratamientos de las afecciones circulatorias cada vez son mejores y se está consiguiendo aumentar la supervivencia de los pacientes tras, por ejemplo, un ataque de miocardio».

[Read more in El Periódico Extremadura]

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