Among those most extensively used in research, the db/db and ob/ob leptin-based models of type 2 diabetes successfully simulate rapid-onset, severe type 2 diabetes and neuropathy, while the high-fat-diet-fed mouse model of diet-induced obesity (DIO) simulates obesity-driven prediabetes and neuropathy (Sullivan et al., 2007; O'Brien et al., 2014a; Hinder et al., 2017). The gene discussed is LEP; the disease is obesity due to melanocortin 4 receptor deficiency.