Lipotoxicity in Non-alcoholic Fatty Liver Disease: Mechanisms and Prevention in Experimental Models

It is estimated that one out of four persons suffers from non-alcoholic fatty liver disease (NAFLD) globally. As a multifactorial process, the development of NAFLD is closely related to obesity, T2DM, cardiovascular diseases and et al, among which the disturbance of lipid metabolism underlies the fundamental pathophysiology of each factor. Specifically, the disturbance of lipid metabolism leads to increased lipid accumulation in the liver and an imbalance between non-toxic and toxic lipids. This imbalance results in lipotoxicity and a deleterious long-term prognosis. Lipotoxicity, as one important hallmark of NAFLD, plays a critical role in the initiation of non-alcoholic steatohepatitis (NASH), the (chronic) inflammatory stage of NAFLD.
In this thesis, we studied lipotoxicity in respect to preventing the lipotoxicity-induced cellular damage using medical interventions and exploring its cellular/molecular mechanisms in the context of NAFLD. We believe that a detailed study on lipotoxicity could help us to better understand the transition from benign steatosis to NASH and to provide novel insights into drug design.