ABSTRACT
Eating is necessary for survival, and humans have powerful biological systems that help to maintain an adequate nutrient supply [1]. These systems involve cross talk between the brain and the rest of the body. The body sends messages to the brain about its energy needs, and the brain responds to these needs through a number of pathways that regulate food intake, energy expenditure, and energy storage in a biological process called energy homeostasis [2-4]. The hypothalamus is the central orchestrator of energy homeostasis. Its interactions with other brain regions and with the periphery help to ensure an adequate energy supply. The arcuate nucleus (ARC) and ventral medial nucleus (VMN) in the hypothalamus have a high density of neurons that respond to peripheral hormones, including leptin, insulin, and ghrelin [5]. The ARC contains two subsets of neurons that play opposing roles in appetite regulation. Pro-opiomelanocorticotropin (POMC) neurons are anorexigenic (i.e., suppress appetite), whereas neurons that coexpress neuropeptide Y (NPY) and agoutirelated peptide (AgRP) are orexigenic (i.e., stimulate appetite) [3]. Arcuate POMC and NPY/AgRP neurons send projections to other areas in the hypothalamus, including the dorsomedial (DMN) and paraventricular (PVN) nuclei of the hypothalamus and the lateral hypothalamic area (LHA), as well as other brain regions involved in regulating energy homeostasis [5]. POMC is cleaved into anorexigenic peptides, including α-melanocyte stimulating hormone (MSH) and cocaine-and amphetamine-regulated transcript (CART). When POMC neurons are activated, α-MSH is released into the PVN, where it acts on melanocortin-3 and 4 receptors to promote satiety. In contrast, NPY/ AgRP neurons activate orexigenic signaling via NPY receptors and inhibit anorexigenic signaling via melanocortin receptors [5-7].
