Using two approaches to suppress Gpr180: AAV9-shRNA Gpr180 and albumin-Gpr180−/−, we showed that hepatic Gpr180 deficiency renders mice resistant to HFD-induced liver steatosis, which is associated with metabolic benefits including enhanced insulin sensitivity and energy metabolism, as well as reduced adiposity. The gene discussed is GPR180; the disease is Hepatic steatosis.