The proposed physiological role of CART as an endogenous anorexigenic factor was originally deduced from the inhibition of food consumption observed in animal models following hypothalamic or intracerebroventricular administration of CART-derived peptides (Kristensen et al., 1998; Vrang et al., 1999b; Larsen et al., 2000; Volkoff and Peter, 2000; Aja et al., 2001a,b; Stanley et al., 2001; Nakhate et al., 2011, 2013). Based on the dual involvement in both hypothalamic modulation of feeding behavior and autonomic control of gastrointestinal functions common to many neuropeptides, considerable efforts have subsequently been devoted to the investigation of CART-mediated effects in the enteric nervous system (ENS) (Couceyro et al., 1998; Kuhar and Yoho, 1999; Murphy et al., 2000; Okumura et al., 2000; Ekblad et al., 2003; Ellis and Mawe, 2003; Smedh and Moran, 2003; Tebbe et al., 2004). Extensive CART expression has been characterized in the ENS of diverse mammals by in situ hybridization (Ekblad et al., 2003) and immunoassays (Couceyro et al., 1998; Kuhar and Yoho, 1999; Murphy et al., 2000; Ellis and Mawe, 2003; Kasacka et al., 2012), affirming the presence of CART mRNA and peptides in nerve cell bodies and fibers innervating the stomach, small and large intestines of the gastrointestinal tract (Ekblad, 2006), particularly within the neuroendocrine cells and myenteric plexus (Kasacka et al., 2012). Such brain-gut CART expression suggests that CNS control of feeding and satiety may be coordinated with local gastric CART-induced effects to produce an integrated regulation of body weight. This is supported by the central CART immunoreactivity profile, which depicts concentrated expression at the hypothalamic nuclei (Spiess et al., 1981; Douglass et al., 1995; Gautvik et al., 1996; Couceyro et al., 1997; Koylu et al., 1997; Smith et al., 1999; Hubert and Kuhar, 2005, 2008; Dominguez, 2006; Vrang, 2006) constituting major relays linking the sensory, motor and limbic areas between forebrain and hindbrain through widespread reciprocal networks, orchestrating autonomic, endocrine and behavioral activities (Fekete et al., 2000; Balkan et al., 2001; Williams et al., 2001; Tebbe et al., 2004). Specifically, anatomical implications of CART indicated by enteric CART expression in digestive function have been further indicated by CART immunoreactivity at the hypothalamic Arc and PVN neurons, as well as brainstem nuclei such as NTS and parabrachial nucleus (PBN), both involved in the efferent and afferent control of GI function through neuropeptidergic mechanisms engaging the complex neuroendocrine and autonomic pathways (Kristensen et al., 1998; Fekete et al., 2000; Aja et al., 2001b; Stanley et al., 2001; Zheng et al., 2001; Tebbe et al., 2003, 2004). In addition, CART expression in the cholinergic neurons of the myenteric plexus and the pancreatic islets further denoted the potential gastric effects of CART conducted via peripheral receptor targets composing the peripheral cholinergic pathways (Couceyro et al., 1998; Jensen et al., 1999; Ekblad et al., 2003; Tebbe et al., 2004; Wierup et al., 2004).