HCRT and obesity due to melanocortin 4 receptor deficiency: Central orexin signaling modulates aspects of peripheral physiology (e.g., blood sugar regulation and adipocity), which are critically linked to obesity and often become dysregulated with age (Cai et al., 1999; Tsuneki et al., 2008, 2012; Sellayah et al., 2011; Inutsuka et al., 2014).