Animals that do not produce prepro-orexin in the brain develop insulin sensitivity, hyperglycemia, and increased susceptibility to diet-induced obesity, all of which escalate in severity with age (Cai et al., 1999; Hara et al., 2005; Tsuneki et al., 2008, 2012; Sellayah et al., 2011). Here, HCRT is linked to obesity due to melanocortin 4 receptor deficiency.