Alternatively, reductions in central insulin action with aging and various pathologic states have also been attributed to a loss of input from impaired insulin transport across the blood–brain barrier (BBB), rather than central insulin resistance per se [25], as saturable insulin transport into the CNS is negatively impacted by obesity [26], T2DM [27], AD [28], and aging [29–31]. Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.