Liver disease regulators discovered
Liver disease regulators discovered © George Hodan

CNIO research team discovers regulators of liver disease

Scientists have discovered that the pharmacological manipulation of AP-1 proteins can help treat fatty liver disease (FLD), also known as steatosis.

Excessive alcohol consumption and obesity leads to the accumulation of fat in the liver. FLD is one of the most prevalent diseases in Western societies and affects about 30% of the adult population. FLD increases the risk of liver failure, diabetes and cancer, and no pharmacological therapies exist for this detrimental disease.

The Genes, Development and Disease research team led by Erwin Wagner, head of the BBVA Foundation-Spanish National Cancer Research Centre (CNIO) Cancer Cell Biology Programme, in collaboration with Johan Auwerx from EPFL in Switzerland, have discovered novel factors in AP-1 proteins, which are critically involved in FLD pathogenesis.

The CNIO team found that the AP-1 gene Fra-1 is reduced in the liver of obese mice. To study the functional contribution of these proteins to fat metabolism in the liver, researchers used transgenic mice with increased or decreased AP-1 expression in the liver.

Strikingly, increased expression of some of these genes, such as Fra-1 or Fra-2, in the liver of mice completely prevented the accumulation of fat and FLD.

Lead author Sebastian Hasenfuss said: “In humans, unhealthy diet is the main cause of FLD. Therefore, we used a fat-rich diet to induce obesity and FLD in mice. When we switched on Fra-1 in the liver, all the fat disappeared.”

In addition, Fra-1 also prevented inflammation and liver damage in obese mice.

The results are featured in Cell Metabolism.