Grant: CIHR Fellowship

The human body uses fats, sugars, and proteins to produce energy or as building blocks in many biological processes. These biochemical reactions lead to the formation thousand of small-molecule intermediates refer to as metabolites. Recent advances in analytic chemistry now allowed researchers to measured a wide array of metabolites in a single biological sample, to produces a metabolic fingerprint called metabolome. Non-alcoholic steatohepatitis or NASH is a serious condition characterized by inflammation and formation of scar tissue in the liver. Patients with NASH are more prone to develop liver failure and cirrhosis, cardiovascular diseases and liver cancer. However, most of them remain undiagnosed and untreated. Presently, the only way to precisely identified patients with NASH is to perform a liver biopsy, which is an invasive and costly procedure. Moreover, no treatments are currently available. Altogether this shows the important need of further medical research in this field. We recently measured metabolome of severe obese patients to identified circulating biomarkers for non-alcoholic fatty liver disease (NAFLD). We identified a class of molecule produced from amino acids transformation in the liver and we show that their blood levels were closely associated with the degree of hepatic lipid content and the presence of NASH. We are actually working to confirm these results in a larger cohort, in order to develop a novel diagnostic tool that will allow clinicians to rapidly identified patients with NAFLD. The candidate will actively participate in the design and the realization of this study. Moreover, he will use advanced genetic tools to reactivate amino acid metabolism in the liver, to ultimately establish the effect on lipid accumulation, inflammation, and formation of scar tissues in different animal models. Our preliminary results show promising outcomes that could rapidly lead to the development of novel strategies to treat patients with NASH.