New way to predict and diagnose nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease affects 25% of the population. In the most severe cases, it can lead to cirrhosis and carries an increased risk of cancer. It has become one of the main causes of liver transplantation.

The DIAMET group of the Pere Virgili Health Research Institute (IISPV) of Tarragona (internationally recognized for its research on the role of succinate in metabolic diseases) has been working in this field for some time.

A new study led by the Pere Virgili Health Research Institute (IISPV) of Tarragona, in collaboration with the Center for Network Biomedical Research on Diabetes and Associated Metabolic Diseases (CIBERDEM), in Spain, has made it possible to identify succinate as a new biomarker present in in the blood to predict nonalcoholic fatty liver disease and to confirm its diagnosis.

The authors of the study have analyzed the levels of succinate in the blood of patients suspected of having the disease and who presented various metabolic disorders (such as obesity) or abnormal values ​​related to glucose, liver enzymes and lipids. Results have shown that patients with elevated blood levels of this metabolite are at increased risk of developing fatty liver disease. In addition, it has been observed that succinate has a similar potential to other non-invasive biomarkers for the prediction and confirmation of the diagnosis of this pathology. The inclusion of this parameter in clinical practice could avoid liver biopsies, an invasive test that is used when there are doubts about the evolution of the pathology.

Researchers of the DIAMET Group of the IISPV. From left to right: Victoria Ceperuelo Mallafré, Anna Marsal Beltran and Sonia Fernández-Veledo. (Photo: IISPV / CIBERDEM)

On the other hand, the succinate receptor, SUCNR1, has been found to play a key role not only in more advanced stages of the disease such as fibrosis, as described in previous studies, but also in earlier stages. Using samples from patients with severe obesity and with different levels of the disease, as well as studies in mice and experiments with cells, it has been shown for the first time that succinate, through its receptor, has protective effects on the main cells of the liver. , the hepatocytes, since it prevents the accumulation of fat in the liver. This protective effect is essential in the initial stages, but it is not enough in more advanced stages.

The excellence and international recognition of the DIAMET Research Group of the IISPV-CIBERDEM-URV, under the direction of the researchers Sonia Fernández-Veledo and Joan Vendrell, materialize in this finding, which not only contributes to a more effective diagnosis of the disease of non-alcoholic fatty liver disease, but it will also open up new avenues for the development of drugs for its treatment (until now non-existent).

Study researchers Victoria Ceperuelo Mallafré and Anna Marsal Beltran point out the importance of advancing in the knowledge of the molecular processes that determine the progression of the disease and being able to develop drugs directed at specific cells.

This study, which has had the participation of other CIBERDEM teams as well as the Network Biomedical Research Center for Physiopathology of Obesity and Nutrition (CIBEROBN) and the Network Biomedical Research Center in the Thematic Area of ​​Liver and Digestive Diseases (CIBEREHD), in Spain, has been carried out with samples from patients from the Joan XXIII and Sant Joan de Reus university hospitals in Tarragona, the Dr. Josep Trueta University Hospital in Girona and the Virgen de la Arrixaca University Clinical Hospital, in Murcia.

The study is titled “Protective effects of the succinate/SUCNR1 axis on damaged hepatocytes in NAFLD”. And it has been published in the academic journal Metabolism. (Source: CIBERDEM / IISPV)