These metabolic shifts result in: (i)Elevated leptin and decreased adiponectin, which impair ERα expression [137]; (ii) Mitochondrial dysfunction and ROS accumulation, damaging estrogen receptors and coactivators [138,139]; (iii) Reduced cholesterol bioavailability for steroidogenesis, particularly under conditions of dyslipidemia and AGE accumulation [61,140,141]. Here, ESR1 is linked to metabolic syndrome.