Based on physiological and signaling data, and the small size of our bioactive peptides, we hypothesized that they may be able to circumvent the transport defects associated with the leptin resistance seen in common obesity, and in a manner similar to leptin, achieve their effects on energy balance and glucose homeostasis through the activation of central leptin receptors known to be concentrated in specific nuclei in the hypothalamus. This evidence concerns the gene LEPR and obesity due to melanocortin 4 receptor deficiency.