Galanin-Like Peptide Stimulates Food Intake via Activation of Neuropeptide Y Neurons in the Hypothalamic Dorsomedial Nucleus of the Rat

Abstract

Galanin-like peptide (GALP), a 29-amino-acid neuropeptide, is located in the hypothalamic arcuate nucleus (ARC), binds to galanin receptor subtype 2, and induces food intake upon intracerebroventricular (icv) injection in rats. However, neural mechanisms underlying its orexigenic action remain unclear. We aimed to identify the nuclei and neuron species that mediate the food intake in response to icv GALP injection. Intracerebroventricular injection of GALP, as powerfully as that of neuropeptide Y (NYP), increased food intake for the initial 2 h. GALP injected focally into the dorsomedial nucleus (DMN), but not the ARC, lateral hypothalamus, or paraventricular nucleus (PVN), stimulated food intake for 2 h after injection. In contrast, galanin injected into the DMN had no effect. DMN-lesion rats that received icv GALP injection showed attenuated feeding compared with control rats. In from the porcine intestine (1). It is widely distributed in the central and peripheral nervous systems and has various activities, including regulation of feeding behavior, cognition, nociception, and secretion of pituitary hormones (2-4). Three distinct galanin receptor subtypes, GalR1, GalR2, and GalR3, have been identified (5). These receptors show different tissue distributions: GalR1 is expressed mainly in the central nervous system, whereas GalR2 abundantly and GalR3 at low levels are expressed in both the central nervous system and peripheral tissue.Galanin-like peptide (GALP), a 60-amino-acid peptide whose residues 9 -21 are identical with galanin-(1-13), was isolated from the porcine hypothalamus (6). GALP has a higher affinity for GalR2 than GalR1. Therefore, GALP was initially suggested to be the endogenous ligand for GalR2 (6). Later, it was reported that the action of GALP in the hypothalamus was observed in GalR2-deficient mice (7). Thus, the receptor for GALP remains to be clarified. Several actions of GALP have been shown. Intracerebroventricular (icv) injection of GALP stimulates LH secretion, and it is blocked by treatment with antagonists of LHRH (8). In relation to the energy metabolism, GALP-containing neurons express leptin receptors, and deficiency of leptin function is associated with reductions in GALP protein and mRNA expression (9, 10). Gene expression of GALP is positively regulated by leptin, insulin, and thyroid hormone, the hormones implicated in energy metabolism (11,12).It has been reported that GALP mRNA is expressed in the arcuate nucleus (ARC) (9, 13), a feeding regulatory center, and that icv administration of GALP increases food intake in rodents (14), although the underlying mechanisms remain largely unknown. The present study aimed to identify the nucleus and neuron species that serve as effectors for the orexigenic action of GALP in rats. First, the target nucleus was studied using the following methods. The effects of focal injections of GALP into several hypothalamus nuclei on food intake were examined. Whether destruction of specific nucleus affects orexigenic effect of icv GALP injection wa...

Galanin-like peptide: a key player in the homeostatic regulation of feeding and energy metabolism?

“…56 Furthermore, inhibition of endogenous NPY or NPY receptors suppresses GALP-induced acute orexigenic effect in rats. 55 These findings suggest that GALP promotes feeding behavior through suppression of the anorexigenic pro-opiomelanocortin system and NPY release from the DMH. Our recent experimental data suggest that the orexigenic actions of GALP are mediated by orexin in the LHA, based on the electromicroscopic observation that GALP-positive axon terminal appears to have made synapse with orexinpositive perikaryon and dendritic process in the rat LHA.…”

“…54 NPY release in the DMH has been proposed to have a role in mediating the effects of GALP on feeding regulation, 55 although another study reported no such effect. 56 Furthermore, inhibition of endogenous NPY or NPY receptors suppresses GALP-induced acute orexigenic effect in rats.…”

“…42 However, injection of GALP into the LHA fails to stimulate feeding. 55,56 One possible explanation is that the distribution of orexin is different within the LHA, which is long between rostral and caudal part. 57 Therefore, it is not yet known whether a position for infusions is suitable.…”

Neuroendocrine integration of nutritional signals on reproduction

“…However, it does not appear ARC POMC/CART or NPY/ AgRP neurons are involved in mediating GALP's effects on fertility, as GALP was not able to directly modulate their activity (Kuramochi et al 2005). In contrast, NPY neurons in the dorsomedial nucleus of the hypothalamus were shown to mediate GALP's acute orexigenic feeding actions (Kuramochi et al 2006), suggesting GALP and NPY neurons may exhibit bi-directional communication to coordinate their effects on feeding behavior and fertility.…”

Galanin-like Peptide Ameliorates Obesity by Control of Food Intake and Energy Metabolism

“…Anti-obesity Effect of GALP GALP was initially described as an orexigenic neuropeptide given that administration of GALP into the brain induces food intake for the first hour thereafter in rats [35][36][37][38]. We previously reported that c-Fos immunoreactivity is increased in orexin-immunoreactive neurons in the LH after the central administration of GALP [39].…”