ER stress induces the activation of the unfolded protein response, which disrupts the leptin signaling pathway, accelerating atherosclerosis development and its complications.<h4>Objective</h4>Indole-3-carbinol (I3C) improves metabolic dysfunction in diet-induced obesity; however, its role in protecting against ER stress-induced hyperleptinemia remains unclear. The gene discussed is LEP; the disease is atherosclerosis.