In this model of NASH, we identified a gradual increase in both endogenous (HMGB1, uric acid, ATP) and exogenous (LPS) danger signals along with up-regulation of their respective receptor sensors, supporting that multiple cumulative danger signals from metabolic insult results in the progression of NAFLD to NASH, fibrosis and liver tumors. Here, HMGB1 is linked to metabolic dysfunction-associated steatohepatitis.