Medical Research Council - London Institute of Medical Sciences

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A Different Death

Understanding more about the mechanisms underlying non-alcoholic fatty liver disease

27 October 2022

A Different Death

Liver diseases are a significant health concern, with non-alcoholic fatty liver disease (NAFLD) estimated to affect around 30% of the global population, across multiple conditions associated with excess fat deposits. Necroptosis, a type of programmed cell death that activates the immune system and causes inflammation, was thought to be generally involved in liver disease, but recent evidence refutes this idea. In mice, disease triggers like viral infection, malarial parasites or high-fat diets still lead to liver disease, progressing as expected, even when the mice lack MLKL, a protein necessary for necroptosis; in the liver tissue pictured, collagen build-up (in red) reveals signs of NAFLD, without necroptosis. Scientists also found that another protein required for necroptosis, RIPK3, is silenced in the liver cells, of both mice and humans, suggesting this process cannot occur there. Together, these findings should shift the focus of research into the mechanisms behind liver disease.

Written by Emmanuelle Briolat

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