In the present study, an animal model of T2DM with leptin receptor defect was used to demonstrate that Zn deficiency significantly exacerbates obesity-induced cardiac oxidative damage, inflammation, and fibrosis in diabetes, effects associated with significantly decreased expression of Nrf2 and the downstream antioxidants NQO-1 and CAT. The gene discussed is LEPR; the disease is obesity due to melanocortin 4 receptor deficiency.