However, the increasing prevalence of obesity and T2DM, as well as their culmination in HFpEF, led us to use leptin receptor-deficient db/db mice as our preclinical model for this study, as these mice develop obesity by 4 weeks of age, T2DM by 12 weeks, and HFpEF by 24 weeks [14]. Here, LEPR is linked to obesity due to melanocortin 4 receptor deficiency.