Moreover, hepatocyte-specific GPER1 knockout (GPER1-HKO) in female and male mice exacerbated HFD- or high-fat and high-cholesterol (HFHC) diet-induced lipid accumulation, inflammatory response, fibrosis, or insulin resistance in mouse NAFLD/NASH models. This evidence concerns the gene GPER1 and metabolic dysfunction-associated steatohepatitis.