The genetically induced hyperphagia and obesity in db/db mice, ob/ob mice, BTBR.Cg-Lepob/WiscJ ob/ob (BTBR ob/ob) mice and Zucker obese fa/fa rats are associated with the development of insulin resistance, Type 2 diabetes mellitus (T2DM), and altered leptin signaling. The gene discussed is LEP; the disease is Insulin resistance.