ESR1 and metabolic dysfunction-associated steatotic liver disease: In the hepatocytes, estrogens, mainly acting through ERα, limit gluconeogenesis (241, 288) preventing increased HGP and insulin resistance (288), limit the uptake of FFAs, inhibit DNL (153) and promotes FA oxidation (289) and export (287), thus preventing lipid deposition in the liver and the generation of lipotoxicity and ROS (252) that trigger a pro-inflammatory response acting as the driver of NAFLD progression and liver degeneration (81, 247).