However, it was observed that overnutrition-mediated activation of IKKβ/NF-κB was activated intracellularly by ER stress and prompted both hypothalamic leptin and insulin resistance through the induction of suppressor of cytokine signaling 3 (SOCS3), an inhibitor of leptin and insulin signaling (95, 101). The gene discussed is LEP; the disease is Insulin resistance.