In any case, the present study clearly showed that exogenous ANP—even at a dose that does not affect either blood pressure or body weight—may still have a significant influence on the “metabolic tissues”, such as adipose tissues and the liver, leading to the improvement in HFD-induced insulin resistance, the cornerstone of the pathophysiology of obesity. This evidence concerns the gene NPPA and obesity due to melanocortin 4 receptor deficiency.