As knowledge of the neuronal networks that regulate energy balance has expanded, the view of functional anatomic centers has been replaced by the concept that discrete neuronal populations underlie such control mechanisms. These neurons express neurotransmitters that mediate particular effects on energy homeostasis and are in turn regulated by specific signals of nutritional state. In the next section, we discuss the neurotransmitter and neuropeptide systems.

Information about nutrient stores, satiety, hunger, and palatability of food is communicated from the periphery to the brain, where it is integrated and translated into appropriate changes in energy balance. These responses are mediated via activation or inhibition of discrete neurotransmitter and neuropeptide signaling pathways expressed in the hypothalamus and other brain regions. A number of these neurotransmitters and neuropeptides have been shown to increase food intake when administered into the CNS, whereas others have been shown to decrease food intake, and some of these peptides and transmitters have differing effects depending on the site of exposure. Table 1 details the peptides implicated in the pathways controlling this complex neuronal circuitry.

Many of these neurotransmitters have been found within discrete neuronal populations within the hypothalamic nuclei described above. For example, neuropeptide Y (NPY) and agouti-related peptide (AgRP), both potent stimulators of food intake, are colocalized in a population of neurons in the ARH (although NPY is expressed in many other sites as well), and a-mel-anocyte-stimulating hormone (a-MSH) and cocaine-and amphetamine-regulated transcript (CART), which induce an anorectic response, are colocalized in an adjacent set of ARH neurons. The PVH is rich in terminals containing numerous appetite-modifying neurotransmitters, including NPY, a-MSH, serotonin, galanin, noradrenaline, and the opioid peptides. Within the LHA there is a defined subpopulation of neurons that express orexins and melanocortin-concentrating hormone (MCH), peptides that stimulate food intake. NPY nerve terminals are abundant in the LHA, in contact with orexin and MCH-expressing cells.

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