These results provide novel insights on the roles of caspase-11-GSDMD pathway in promoting hepatic macrophage inflammation and pyroptosis and novel targets for future therapeutic interventions involving transition of NAFLD to NASH, hyperlipidemia, type-II diabetes, metabolic syndrome, atherosclerotic cardiovascular diseases, autoimmune diseases, liver transplantation, and hepatic cancers. Here, GSDMD is linked to metabolic dysfunction-associated steatohepatitis.