12 - dic. - 2016
The following 21st of December will take place the third session of the Programme Progress Reports given by Paula Iruzubieta Coz, specialist in Digestive System at Marques de Valdecilla University Hospital.
The session will be about “The liver-specific deletion of the respiratory chain inhibitor MCJ attenuates NAFLD progression by enhancing hepatic beta-oxidation” and is summarized briefly below:
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.
This programme of seminars is given by young researchers on the field of IDIVAL’s clinic and laboratories. The speakers will explain the scientific advances of their current research projects. With the idea of debating and networking, the main goal of the meeting, all the predoctoral contracts, Post-MIR Valdecilla López Albo researchers, Río Hortega and Inn-Val grants are invited to attend to the sessions as part of their training.
The meeting will take place in lecture room 4-5, pavilion 16 of the HUMV (the lecture room has a capacity of 30 people).
Researchers who attend 80% of the meetings throughout the academic year will receive a certificate of assistance.