21 de Diciembre Tercera Sesión Progress Reports impartida por Paula Iruzubieta

Non-alcoholic fatty liver disease (NAFLD) is a spectrum of liver disease that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. NAFLD is strongly associated with features of metabolic syndrome and it has rapidly become the most common cause of liver dysfunction in many developed and developing countries, in line with increasing prevalence of obesity. NAFLD is associated with an increased overall mortality compared with the general population, and NASH is associated with a high risk of liver-related death and cardiovascular disease. The molecular mechanisms underlying NAFLD progression are complex and not completely understood, thus no specific pharmacological therapy currently exists. Mitochondria are the main energy source in hepatocytes and play major roles in oxidative metabolism and normal function of the liver. Notably, mitochondrial dysfunctions have been described in NAFLD. MCJ (methylation-controlled J-protein) is localized at the inner mitochondrial membrane where it binds and inhibits the electron transport chain complex I. In this work, we studied the role of MCJ in the pathogenesis of NAFLD and investigated the effect that the absence of MCJ exerts in the progression of the disease. Interestingly, we found that MCJ expression is increased in human NAFLD. Moreover, MCJ silencing protected against hepatic lipid accumulation and inflammation in the methionine-choline deficient diet mouse model of NASH. Loss of MCJ led to increased β-oxidation and enhanced mitochondrial respiration, Tricarboxylic acid (TCA) cycle function and glycolysis rate, which maintained mitochondrial function and ATP production. These metabolic adaptations were able to counteract the cytotoxic effects of fat accumulation on mitochondria and ultimately on hepatocytes. Overall, MCJ emerges as a key regulator of NAFLD paving the way for new therapeutic approaches.

En este programa de seminarios impartidos por investigadores jóvenes del ámbito clínico y de los laboratorios IDIVAL, se expondrán los avances científicos que están desarrollando dentro de los proyectos de investigación en los que participan. Por ello y para favorecer el debate y networking, objetos clave de la charla, se insta a participar a jóvenes con contratos predoctorales, investigadores Post-MIR Valdecilla López Albo, Río Hortega y becas Inn-Val como complemento de su formación.

La sesión tendrá lugar a las 14:30 en el aula 4-5 del Pabellón 16 del Hospital Universitario Marqués de Valdecilla (aforo máximo de 30 personas). 

Se emitirán certificados de asistencia si se acude al 80% de las sesiones a lo largo del periodo académico.