Spanish study finds key to nonalcoholic fatty liver disease

Researchers from the CiMUS Molecular Metabolism group at the University of Santiago de Compostela (USC) and the CIBER of Obesity and Nutrition (CIBEROBN) have discovered a new target involved in the development of non-alcoholic fatty liver disease for which, for the moment, there is no treatment.

It involves the ATG3 protein, which is present at high levels in the. liver of patients with this pathology, and that, by inhibiting it, it improves fat metabolism by increasing mitochondrial function while decreasing the fat accumulation and damage to this organ.

Several studies have shown that this disease is suffered by one in four people in the world today, which means almost two billion people affected. In the early stages this disease starts with fat accumulation in the liver (5% fat is enough to classify the liver as fatty), and can progress to more serious diseases, including steatohepatitis nonalcoholic fatty liver disease, cirrhosis and cancer. The increasing prevalence of nonalcoholic fatty liver disease in both developed and developing countries has made it the most common cause of liver transplantation.

For the conduct of this study, published in the scientific journal ‘Journal of Hepatology‘, a cohort of 117 human patients, 85 with different stages of fatty liver disease and 32 patients with healthy liver, was used.

“The use of human samples from up to 117 patients is a strength of the work because. it helps to verify that our discovery in preclinical models has validity. and can potentially be applicable to humans, and it also involves a tremendous coordination effort by specialists from three national hospitals: Santa Cristina University Hospital (Madrid), Marqués de Valdecilla University Hospital (Santander) and Virgen del Rocío University Hospital (Seville),” explain the CiMUS researchers involved in this work.

The results showed that patients with nonalcoholic fatty liver disease have elevated levels of ATG3 in the liver, a protein which until now was known for its role in autophagy, a process by which the cell destroys unusable cellular material. The same was observed in the liver of mice fed a high-fat diet, as well as in human liver cells.

“We have managed to demonstrate a mechanism of reversal of fat accumulation in the liver, making ATG3 a possible therapeutic target against non-alcoholic fatty liver disease,” say the lead authors of the research, Natália Lima, Marcos Fernandez Fondevila and Eva Nóvoa. This is because ATG3 inhibition causes the increase of Sirtuin 1 (SIRT1) and Carnitine Palmitoyltransferase 1 a (CPT1a), two proteins involved in mitochondrial function.

This research is the result of the work of researchers Natália da Silva Lima, Marcos Fernandez Fondevila and Eva Nóvoa Deaño. from the Molecular Metabolism group of CiMUS, coordinated by Dr. Rubén Nogueiras Pozo and with the participation of CiMUS research teams (Dr. Miguel López and Dr. Carlos Diéguez), as well as groups from the University of the Basque Country, CIC bioGUNE (Bilbao), the European Genomic Institute for Diabetes (France), CNIC (Madrid), University of Coimbra (Portugal), University of Lübeck (Germany), Santa Cristina University Hospital (Madrid), August Pi iSunyer Biomedical Research Institute (Barcelona), as well as CIBEREHD and CIBERDEM.