Steatohepatitis is the inflammation and accumulation of fat in the liver and is implicated in the onset of most cases of cirrhosis. Researchers from the University of Navarra and the University of Southern California at Los Angeles (USCLA) have shown that the absence of the MAT1A gene causes this disease.

This study, published in the journal Proceedings of the National Academy of Sciences USA, was led by Professors José Mª Mato, Matías Ávila and Fernando Corrales (all from the University of Navarra); and Professor Shelly L. Lu, from USCLA. Dr. Luis Álvarez (Hospital Universitario La Paz, Madrid) also collaborated in the project .

According to Dr. Mato, previous work "had shown that, in patients with cirrhosis caused by alcohol or hepatitis B or C viruses, MAT1A gene expression is markedly reduced, and is even lower in patients with more advanced cirrhosis. But we didn't know whether it was a cause or a consequence of liver disease."

Essential gene in the onset of liver disease

That is why," he continues, "we eliminated the MAT1A gene in mice, which is the main gene manager for the hepatic synthesis of S-adenosylmethionine (SAM). Using DNA chip techniques, we demonstrated that the decrease in the hepatic levels of SAM in the mice produced alterations in the expression of numerous genes responsible for maintaining the structure and function of the liver".

Thus, the mice "not only developed steatohepatitis, but were found to be more susceptible to liver damage induced by various hepatotoxic agents," explains the expert.

Dr. Mato concludes, "These results, together with previous work from our laboratory showing that SAM treatment increases survival in patients with alcoholic cirrhosis, indicate that deficiency in MAT1A gene expression plays an essential role in the onset of liver disease."