Decoding non-coding RNAs in fatty liver disease

Non-alcoholic fatty liver disease (NAFLD) encompasses a range of liver disorders, from simple deposition of fat in the liver (hepatic steatosis) to more severe phenotypes characterized by the presence of inflammation, ballooning and fibrosis (non-alcoholic steatohepatitis or NASH). Obesity is the major risk factor for NAFLD and, driven by the global obesity epidemic, NAFLD has become the leading cause of chronic liver disease worldwide. 10-20% of NASH patients will progress further towards cirrhosis and hepatocellular carcinoma (HCC) which, in view of their increasing prevalence, will become frequent indications for liver transplantation. It is therefore important to understand the mechanisms involved in NAFLD etiology, in order to prevent its development as well as its progression towards more severe conditions. It has been estimated that more than 98% of human genome is now considered as the non-coding genome. Interestingly, a large part of non-coding genome is found to be transcribed into non-coding RNAs (ncRNAs) that can participate in a number of critical biological processes, such as chromatin remodeling, gene transcription and protein transport and trafficking, thus implicating ncRNAs in a wide range of complex human diseases. However, the involvement of ncRNAs in the liver and in NAFLD development and progression is not well understood. In this thesis we aim to understand the role of ncRNAs in NAFLD by combining transcriptome profiling in a patient cohort, functional genomics in in vitro models to mimic disease progression, and follow-up functional studies using various molecular techniques. This research highlights the importance of ncRNAs in NASH