For this reason, in this study, we used male and female SST- and CORT-KO mice fed a LF or a HF diet to thoroughly explore, for first time, the interplay between SST or CORT and obesity in the control of the most relevant pituitary hormonal axes and whole-body metabolic function (the main results are summarized in Table 1) and found striking differences that may help to shed light to the role of endogenous SST and CORT in the control of the endocrine/metabolic milieu under extreme metabolic conditions. The gene discussed is CORT; the disease is obesity due to melanocortin 4 receptor deficiency.