Caspase-11 deficiency reprograms liver transcriptomes and attenuates hepatic macrophage pyroptosis in HFD-induced NAFLD; caspase-11 cleaves N-terminal GSDMD in normal chow diet livers more than that in HFD-induced NAFLD; and bone marrow-derived macrophages play more significant roles than liver resident macrophages in facilitating pyroptosis. The gene discussed is GSDMD; the disease is metabolic dysfunction-associated steatotic liver disease.