Abstract
The Neuropeptide S (NPS), a 20 amino acids peptide, is recognized as the endogenous ligand of a previously orphan G protein-coupled receptor, now termed NPS receptor (NPSR). The limited distribution of the NPS-expressing neurons in few regions of the brainstem is in contrast with the extensive expression of NPSR in the rodent central nervous system, suggesting the involvement of this receptor in several brain functions. In particular, NPS promotes locomotor activity, behavioral arousal, wakefulness, and unexpectedly, at the same time, it exerts anxiolytic-like properties. Intriguingly, the NPS system is implicated in the rewarding properties of drugs of abuse and in the regulation of food intake. Here, we focus on the anorexigenic effect of NPS, centrally injected in different brain areas, in both sated and fasted animals, fed with standard or palatable food, and, in addition, on its influence in the gastrointestinal tract. Further investigations, regarding the role of the NPS/NPSR system and its potential interaction with other neurotransmitters could be useful to understand the mechanisms underlying its action and to develop novel pharmacological tools for the treatment of aberrant feeding patterns and obesity.
Highlights
Despite the large number of regions implicated in eating behavior, the hypothalamus is considered as the main feeding center for the control of appetite, in which a great number of neuropeptides is involved in the modulation of food intake and body weight [3,4,5]
Using in situ hybridization studies, the highest levels of the NPS receptor (NPSR) mRNA were found in the cortex, thalamus, hypothalamus, parahippocampal formation, including the subiculum and amygdala, while less expression was detected in the brainstem, and no NPSR transcript was found in Neuropeptide S (NPS) precursor-expressing cells [15,21]
Following ICV injections of NPS, c-Fos immunoreactivity was detected in the lateral hypothalamus (LH), perifornical area (PeF) and DMH, brain regions that are considered important sources of orexin-A projecting neurons, and a measurable expression of NPSR mRNA was detected in orexin-A positive cells of the LH [54,103,104]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. Despite the large number of regions implicated in eating behavior, the hypothalamus is considered as the main feeding center for the control of appetite, in which a great number of neuropeptides is involved in the modulation of food intake and body weight [3,4,5]. The interaction among these peptides in the central nervous system (CNS) results in a complex regulation of food intake and, the dysregulation of their neurotransmission can contribute to increased appetite, weight gain, and obesity [6]. We will first describe the most important biological, neuroanatomical, and pharmacological features regarding the NPS system, and we will focus on the role played by the NPS and its receptor on food consumption, revising the current literature linking this system to feeding behavior, considering that it could represent an important pharmacological target to treat obesity and eating disorders
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