It is our view that the widespread use of this model should be questioned, given that: (1) The Zucker diabetic rat lacks functional leptin receptors (fa/fa genotype), because leptin receptor deficiency is infrequently seen in obese and T2D humans since leptin receptor mutations are relatively rare [28]; (2) we have shown here that Zucker diabetic rats do not exhibit an overactivation of the sympathetic nervous system, probably due to the absence of leptin receptors, which is generally accepted to be a principle driver of obesity and metabolic-related illness [14,15,29]. This evidence concerns the gene LEPR and obesity due to melanocortin 4 receptor deficiency.