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A team co-led by scientists at IRB Barcelona and IDIBAPS Hospital Clinic have published a study in Nature Cell Biology revealing the role the CPEB4 protein plays in protecting against non-alcoholic fatty liver disease. This condition, which is becoming increasingly common in western countries, is caused by excessive buildup of fat in hepatic cells and can lead to fibrosis, cirrhosis and liver cancer.

This work opens the doors for studying new therapeutic strategies to prevent and fight this condition, although as it is basic research there is no immediate clinical application. “An increase in those affected by non-alcoholic fatty liver disease is expected in the coming decades and a fundamental understanding of this medical problem is therefore essential for development of novel treatment strategies,” explains co-leader of the study Mercedes Fernández (IDIBAPS). Obesity, lifestyle and ageing are associated with the increased prevalence of this disease.


Results of the study

The scientists eliminated the CPEB4 protein from the livers of mice and observed that, as they aged, the mice developed fatty liver disease. Moreover, young mice that were fed a high-fat diet and depleted of CPEB4 also developed this condition, and in a more pronounced manner.

CPEB4 is essential in driving liver stress response. Under stress caused, for example, by uncontrolled ingestion of fats, the endoplasmic reticulum stops its activity in order to re-establish cell equilibrium. This “clean-up” response is orchestrated by CPEB4 and varies depending on the time of day. In humans, it is more active during the day. However, without CPEB4, the endoplasmic reticulum can’t activate this stress response and the hepatocytes accumulate lipids, leading to fatty liver.

According to co-leader of the study and ICREA researcher at IRB Barcelona Raúl Méndez, understanding how CPEB4 works in the liver could be useful as a predictive marker for those with variants of this protein, helping prevent them from developing fatty liver through better diet and eating times, for example. “Such knowledge could also contribute to the development of treatments that boost the clean-up process,” explains Méndez.

This study has received funding from the Worldwide Cancer Research Foundation in the United Kingdom, Spanish Association Against Cancer, Botín Foundation / Banco Santander Universities, Ministry of Economy and Competitiveness / ERDF funds and the Government of Catalonia.


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