Aerobic perfusion of isolated working hearts from ob/ob mice, db/db mice, mice subjected to experimental obesity via high-fat diet supplementation, or mice and rats subjected to experimental T2D via high-fat diet supplementation plus low-dose streptozotocin administration, demonstrate impaired basal and insulin-stimulated glucose oxidation rates (Buchanan et al., 2005; Hafstad et al., 2006; How et al., 2006; Ussher et al., 2009; Wright et al., 2009; Le Page et al., 2015). This evidence concerns the gene INS and obesity due to melanocortin 4 receptor deficiency.