These HFD outcomes, observed here, confirm that we have an obesity mice model and lead us to believe that the specific deletion of TF HNF4α in the β-cells of the pancreas may trigger systemic changes that are important for an adaptive response to obesity, probably due to the lack of the expected physiological amount circulating insulin in the knockout mice. Here, HNF4A is linked to obesity due to melanocortin 4 receptor deficiency.