NEUROPEPTIDE Y (NPY) was identified as a neuropeptide that is colocalized and coreleased with the neurotransmitter norepinephrine from sympathetic nerve terminals. In this regard, a large body of research on NPY focused on its role in autonomic physiology and pharmacology as a potentiator of the postsynaptic actions of norepinephrine. However, with the increased understanding of the genes and their encoded proteins involved in the central nervous system regulation of feeding behavior and food intake (9,10,20), there is expanding research on the role of NPY as one of the most potent orexigenic signal molecules in the brain of mammals. Thus application of NPY is a common feeding stimulus (6, 23). Because feeding behavior and food intake are important determinants of the balance between energy intake and energy expenditure in the regulation of body weight, it is not surprising to learn that NPY is also a major regulator of food intake in nonmammalian species, such as the goldfish (Carassius auratus) (22).Uncoupling proteins (UCP) are mediators of thermogenesis that may contribute to the regulation of energy balance. For example, in differentiated adipocytes, UCP-1 is coexpressed with metallothionein, which is strongly expressed during activation of thermogenesis in brown adipose tissue (2). Injection of NPY into the paraventricular nucleus (PVN) of rats increased food intake and this was associated with a decrease in expression of UCP-1 mRNA in brown adipose tissue, whereas the expression of UCP-2 and UCP-3 mRNA in white adipose tissue and skeletal muscle, respectively, was not regulated by NPY. Thus NPY produces a specific and differential regulation of the expression of genes for the UCPs, which, as mediators of thermogenesis, may contribute to the regulation of energy balance (17). The PVN seems to be a crucial region for the control of food intake by different substances (7,8). The increase in food intake produced by injections of NPY into the PVN is blocked by injection of the opioid antagonist naltrexone into the medial portion of the nucleus of the solitary tract (mNTS). It remains to be determined whether this functional pathway from PVN (NPY) to mNTS (opioid) is monosynpatic or multisynaptic (16).A number of peptides control food intake under specific conditions, such as leptin (5,12,24). Contrasting the behavioral responses to NPY and leptin, it appears that NPY stimulates the responses used to obtain food but inhibits those used to consume food [such as gastric emptying (13)], whereas leptin has the opposite effect. In regard to the specificity of the responses, NPYtreated male rats chose to ingest a sucrose solution rather than copulate with a female, whereas leptintreated male rats made the opposite choices. Therefore, NPY is not merely an orexigenic peptide but one that directs attention to food. Leptin may not be an anorexic peptide but one that diverts attention away from food toward alternate stimuli. Under some conditions, leptin seems to inhibit NPY mRNA expression (19). It may be speculated that...