Steatosis, the excessive accumulation of fat in the liver, is one of the most common diseases in developed societies, affecting almost 30% of the adult population. The disease is sometimes caused by obesity, diabetes, or excessive alcohol intake. The consequences can be serious: fatty liver can trigger cirrhosis and hepatic failure, contributes to the development of diabetes, and can lead to liver cancer. There are currently few treatment options for this disease.
Steatosis begins with an excessive accumulation in the liver of triglycerides, which stimulates an inflammatory response. Inflammation in many diseases involves contributions from p38 gamma and p38 delta, and the CNIC team discovered that the livers of obese patients express higher than normal levels of these proteins.
Using mice unable to express p38 gamma and p38 delta in neutrophils, a type of inflammatory cell, the research team showed that these two proteins control the migration of neutrophils to the liver. As the authors explain, "the arrival of these cells is necessary for the accumulation of fat in this tissue."
Therefore, inhibition of neutrophil migration in animals lacking p38 gamma and p38 delta would be enough to protect them from the development of fatty liver, thus preventing inflammation, liver damage, and even diabetes linked to obesity.
The only way to test for hepatic neutrophil recruitment in obese individuals is to take a liver biopsy. With the new discovery, it may become possible to prevent neutrophil infiltration by treating patients with specific inhibitors.