Metabolic disturbances to the liver system can induce lipid deposition and subsequently cause non-alcoholic fatty liver disease (NAFLD). Increasing consumption of fructose has been proposed as a crucial risk component in the development of NAFLD. Three potential therapeutic targets in the network were explored using a composite model of liver function. Introducing a fructose enriched diet under insulin resistance conditions was simulated to evaluate the effectiveness of the model in novel therapy design. In vitro experiments were conducted on rat liver samples to assess the robustness of the model predictions. Synergistic application of all three interventional points in silico has been predicted as the most effective treatment to reduce lipid production under both moderate and severe insulin resistance conditions. This study demonstrates how we can use system models together with in vivo experiments to explore the behaviour of the liver system in response to fructose variation and use it to help identify possible drug targets
