The primary ones that have been utilized to interrogate cardiac substrate metabolism include db/db mice, which exhibit robust obesity, insulin resistance, and a T2D phenotype secondary to spontaneous mutation in the leptin receptor, as well as diet-induced obesity via consumption of a high-fat diet (HFD), which causes insulin resistance and prediabetes in mice. Here, LEPR is linked to obesity due to melanocortin 4 receptor deficiency.