A team co-headed by scientists has revealed the capacity of the CPEB4 protein to prevent fatty liver disease. The results have appeared in Nature Cell Biology.

Non-alcoholic fatty liver is characterised by the accumulation of fat deposits in hepatocytes. The development of this condition is determined by many factors that have not been well described to date. However, obesity and lifestyle, as well as aging, are associated with an increase in the incidence of this disease. Also, a number of large-scale genomics studies have linked variants of the CPEB4 gene with the impairment of fat metabolism.

The scientists depleted CPEB4 expression in mouse livers in order to study the function of this protein. They observed that the mice developed fatty liver as they aged. Furthermore, young CPEB4-depleted mice fed a high-fat diet also developed this condition in a more pronounced manner.

Under stress caused by uncontrolled ingestion of fats for example, the endoplasmic reticulum--a cell organelle associated with protein synthesis and folding and lipid metabolism--stops its activity in order to re-establish cell equilibrium. This "clean-up" mechanism is orchestrated by CPEB4 and varies in function of the time of day--being more active in humans during the day (when the liver has most work) and dropping off at night.

Without CPEB4, the endoplasmic reticulum is unable to activate the stress response, thus causing hepatocytes to accumulate the lipids produced by the fatty liver.

The researchers have managed to reverse fatty liver disease in mice by treatment with a drug called Tudca, which is currently used for other disorders. This drug exerts the same function as the proteins that are activated by CPEB4 and that are responsible for cleaning up the cell, namely chaperones. "In the future it may be possible to design molecules like Tudca that specifically target CPEB4, thus enhancing the liver clean-up process," proposes the author.

https://www.irbbarcelona.org/en/news/researchers-discover-a-protein-that-protects-against-fatty-liver