To investigate whether HIF-2α in macrophages can influence NASH disease progression, we fed Hif2αfl/fl and Hif2αΔLysm mice a GAN diet (40% fat-powered, 20% fructose, and 2% cholesterol) for 24 weeks to compare the severity of inflammation and fibrosis in the liver. Here, EPAS1 is linked to metabolic dysfunction-associated steatohepatitis.