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Researchers discover a protein that protects against fatty liver

By 17 de January de 2017No Comments
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Staining of mouse liver sections showing steatosis of the liver (fatty liver), with accumulation of fat, lipid droplets (in red), within cells. Cell nuclei stain blue (C. Maíllo, IRB Barcelona).
 17.01.2017

Researchers discover a protein that protects against fatty liver

A team co-headed by scientists at the Institute for Research in Biomedicine (IRB Barcelona) and the IDIBAPS Biomedical Research Institute (part of the Hospital Clínic de Barcelona) has revealed the capacity of the CPEB4 protein to prevent fatty liver disease.This condition generally leads to chronic inflammation (non-alcoholic steatohepatitis), which can trigger fibrosis, cirrhosis and ultimately liver cancer. This study on the basic biology of the liver paves the way to examine therapeutic strategies to fight and prevent fatty liver disease. The results have appeared in Nature Cell Biology this week.

 

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 at IRB Barcelona 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.

Carlos Maíllo, first author of the article and PhD student at IRB Barcelona funded by a “la Caixa” grant, has described the molecular function of CPEB4. He reveals that this protein is essential to drive the liver stress response.

Specifically, 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.
 

• More information: IRB Barcelona website [+]