Mathematical Modeling of Free Fatty Acid-Induced Non-Alcoholic Fatty Liver Disease (NAFLD)

Non-Alcoholic Fatty Liver Disease (NAFLD) is the most common type of chronic liver disease in developed nations. Here, we present a generic model of free fatty acid (FFA)-induced NAFLD that constitutes the liver as ensemble of small liver units (LUs) differing in their vulnerability to toxic FFAs and capacities to metabolize FFAs and repair FFA-induced cell damage. The model describes NAFLD as cascading liver failure where failure of few LUs increases the risk for other LUs to fail as well. Model simulations provided the following insights: (1) Persistently high plasma levels of FFAs are sufficient to drive the liver through different stages of NAFLD; (2) Presence of NAFLD amplifies the deleterious impact of additional tissue-damaging hits; (3) Coexistence of non-steatotic and highly steatotic regions is indicative for the later occurrence of severe NAFLD stages.