As introduced earlier, evolutionary conservation has been demonstrated for CART in the neuroendocrine system across various mammalian species in the contexts of isoform structure, expression distribution pattern as well as functional implications, including a role of CART in the regulation of energy balance in human (Hager et al., 1998; Challis et al., 2000; del Giudice et al., 2001; Yamada et al., 2002; Dominguez et al., 2004a; Guerardel et al., 2005; Yanik et al., 2006; Rigoli et al., 2010). First, a genome-wide scan for human obesity-susceptibility loci in obese French Caucasian families (Hager et al., 1998) revealed a clear linkage to the chromosomal locus of 5q13.2 where the human CART gene is encoded (Table 3). Respectively, the expression of CART transcripts and peptides has been characterized in various hypothalamic areas involved in appetite control (Charnay et al., 1999; Elias et al., 2001; Menyhért et al., 2007), as well as in the subcutaneous and visceral white adipose tissues central to the moderation of lipid homeostasis (Vasseur et al., 2007; Banke et al., 2013). Intriguingly, the aforementioned anatomical-functional implications provided by the expression patterns of CART in the human infundibular nucleus, which demonstrated colocalization with the orexigenic NPY/AgRP and segregation from the anorexigenic POMC neurons, had rendered a primary anorectic role of CART appealable (Menyhért et al., 2007).