Mice lacking orexin neurons (orexin/ataxin-3 transgenic mice) or orexin gene (prepro-orexin knockout mice) exhibit a significant reduction in food intake, water intake, locomotor activity, energy expenditure, and unexpectedly late-onset obesity despite their hypophagic phenotype (Hara et al., 2001, 2005; Fujiki et al., 2006; Zhang et al., 2007). This evidence concerns the gene HCRT and obesity due to melanocortin 4 receptor deficiency.