Towards Better Understanding of Non-alcoholic Fatty Liver Disease Through Modelling and Simulation Approaches

摘要

Non-alcoholic fatty liver disease (NAFLD) is a poorly understood complex disorder with a wide prevalence in Western populations with unhealthy dietary and lifestyle habits. Systems biology tools may provide further insight into the multi-dimensional nature of NAFLD. A dynamic semi-quantitative model of the metabolic and signaling pathways suggested to be important in the pathogenesis of NAFLD has been generated using an object-oriented library of components based on differential equations. The analysis of the enzyme reaction model in steady state identified independent model parameters and a system of equations that closely represent biological reactions, by stressing an importance on the partition of metabolic fluxes at pathway branch points rather than the initial metabolic flux through the system. Model validation procedures have suggested a close correlation between experimental observations and the in silico network. Moreover, the simplification of the model has identified the core metabolic pathways and regulatory mechanisms that are potentially deregulated in NAFLD.