Hypothalamic neuronal networks and feeding-related peptides involved in the regulation of feeding

The hypothalamus is a region of the brain that plays a critical role in feeding regulation. It has been revealed by various physiological experiments that the feeding-regulating center is confined to the ventromedial hypothalamus, lateral hypothalamus (LH) and arcuate nucleus (ARC). Many kinds of neurons in these areas of the hypothalamus express factors such as melanin-concentrating hormone (MCH), neuropeptide Y (NPY), proopiomelanocortin (POMC), orexin (OX) and ghrelin, which have been implicated in feeding regulation. In tissues of the periphery, two critical factors involved in feeding regulation, leptin and ghrelin, have been identified. Both hormone peptides are secreted mainly from adipose and stomach tissue, respectively, and are considered to function via their receptors mainly through several hypothalamic nuclei that play important roles in the regulation of appetite. The present review looks mainly at the functional significance of feeding-regulation factors, such as those described above, and the humoral and neuronal interactions among these compounds in the hypothalamus by drawing on published reports of morphological and physiological analyses. Immunohistochemical and in situ hybridization experiments indicate that both leptin and ghrelin receptors are distributed in the hypothalamus and that there are reciprocal interactions between MCH and OX neurons in the LH. Morphological and physiological studies on single living cells isolated from fresh rat hypothalamus or with receptor agonist and antagonist combined with immunohistochemisry clearly demonstrate that both leptin and OX reciprocally regulate NPY- and POMC-containing neurons in the ARC and that ghrelin may regulate feeding status independently through direct OX and NPY pathways. In this way, cross-talking systems in the hypothalamus play a role in determining feeding states.