Two separate populations of neuronal cell types are located in the mammalian arcuate nucleus (ARC, equivalent of infundibular nucleus in avian species); one synthesizes the powerfully orexigenic peptides (neuropeptide Y, NPY and agouti-related peptide, AgRP), while the other produces the anorexigenic pro-opiomelanocortin (POMC) and cocaine and amphetamine-regulated transcript (CART) [5] (Fig. 4.1). In both mammals and avian species, NPY is one of the most potent appetite stimulators. Central administration of NPY increases energy intake, decreases energy expenditure, and enhances adipogenesis and lipogenesis (de novo fatty acid synthesis, see chapter 9, section 9.4) [6^-9]. Repeated central NPY administration induces obesity within a matter of days [10]. The effects of NPY on feed intake are mainly mediated via NPY receptor 2 (NPY Y2) and 5 (NPY Y5) [11], which belong to G-protein coupled receptors. The search for the underlying mechanism for the agouti obesity syndrome, in part led to the discovery of an endogenous melanocortin receptor (MCR) antagonist, AgRP. AgRP is co-expressed with NPY in the ARC, and when it is released from its neurons, it binds to MC3R and MC4R and, in turn, induces feed intake. Transgenic overexpression of AgRP produces an obesity syndrome [84]. Similarly, genetic deficiency of the MC4R in mice results in hyperphagia and obesity [85]. Unlike rodent models where prolonged effects of AgRP on feed intake have been reported [86], the effects of AgRP in sheep were not apparent after 24h. In pigs, neither AgRP nor SHU9119 (MC4-R antagonist) had any effects on feed intake thought to be due to a mutation in the MC4-R [87]. The expression and activity of NPY and AgRP are increased in conditions associated with weight loss, such as caloric restriction, lactation, and intense exercise [88^-90] of particular interest among central catabolic systems are the melanocortins, neurotransmitters cleaved from the POMC precursor polypeptide. Mice lacking POMC are obese [91] and mutations that cause loss of POMC function in humans produce obesity and insulin resistance [92]. The alpha-melanocyte stimulating hormone (α-MSH), POMC-derived neuropeptide, is an endogenous MCR agonist that reduces feed intake when it acts on MC3R and MC4R [93]. Chronic infusion of α-MSH in the third cerebral ventricle of rats reduced feed intake and body weight [94]. Similarly, central administration of α-MSH suppresses feed intake in chickens [95]. In mammals, β-MSH binds MC4R with higher affinity than α-MSH, however, the opposite (α-MSH has a higher affinity to MC4R than does β-MSH) occurs in chicken [96, 97].