Effects of Kisspeptin-10 on Hypothalamic Neuropeptides and Neurotransmitters Involved in Appetite Control.

Giustino Orlando,Lidia Leporini,Annalisa Chiavaroli,Lucia Recinella,Azzurra Stefanucci,Sheila Leone,Claudio Ferrante,Giorgia Macedonio,Adriano Mollica,Marilisa Dimmito,Luigi Brunetti,Luigi Menghini

doi:10.3390/molecules23123071

Giustino Orlando, Lidia Leporini + Show 10 more

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https://doi.org/10.3390/molecules23123071

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Journal: Molecules (Basel, Switzerland)	Publication Date: Nov 24, 2018
Citations: 38	License type: CC BY 4.0

Affiliation: University of Chieti-Pescara

Abstract

Besides its role as key regulator in gonadotropin releasing hormone secretion, reproductive function, and puberty onset, kisspeptin has been proposed to act as a bridge between energy homeostasis and reproduction. In the present study, to characterize the role of hypothalamic kisspeptin as metabolic regulator, we evaluated the effects of kisspeptin-10 on neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) gene expression and the extracellular dopamine (DA), norepinephrine (NE), serotonin (5-hydroxytriptamine, 5-HT), dihydroxyphenylacetic acid (DOPAC), and 5-hydroxyindoleacetic acid (5-HIIA) concentrations in rat hypothalamic (Hypo-E22) cells. Our study showed that kisspeptin-10 in the concentration range 1 nM–10 μM was well tolerated by the Hypo-E22 cell line. Moreover, kisspeptin-10 (100 nM–10 μM) concentration independently increased the gene expression of NPY while BDNF was inhibited only at the concentration of 10 μM. Finally, kisspeptin-10 decreased 5-HT and DA, leaving unaffected NE levels. The inhibitory effect on DA and 5-HT is consistent with the increased peptide-induced DOPAC/DA and 5-HIIA/5-HT ratios. In conclusion, our current findings suggesting the increased NPY together with decreased BDNF and 5-HT activity following kisspeptin-10 would be consistent with a possible orexigenic effect induced by the peptide.

Highlights

Kisspeptin is a peptide encoded by the metastasis suppressor gene kiSS-1 for melanoma cells [1], isolated from human placenta and acting as endogenous ligand of the orphan G protein-coupled receptor 54 (GPR54, named kisspeptin receptor, kiSS-1R) [2,3,4]
To further characterize the role of hypothalamic kisspeptins as metabolic regulators, we evaluated the effects of kisspeptin-10 on neuropeptide Y (NPY) and brain-derived neurotrophic factor (BDNF) gene expression and the extracellular DA, NE, and 5-hydroxyindoleacetic kisspeptin-10 concentration-independently increased the (5-HT) concentrations in rat hypothalamic (Hypo-E22) cells
Our study revealed that 5-hydroxyindoleacetic kisspeptin-10 concentration-independently increased the (5-HT)

Summary

Introduction

Kisspeptin is a peptide encoded by the metastasis suppressor gene kiSS-1 for melanoma cells [1], isolated from human placenta and acting as endogenous ligand of the orphan G protein-coupled receptor 54 (GPR54, named kisspeptin receptor, kiSS-1R) [2,3,4]. Kisspeptin has been identified in multiple brain areas including the hippocampus and amygdala [6,7,8]. Kisspeptin neurons are widely distributed in many discrete hypothalamic nuclei in both mouse and rat, including the anteroventral periventricular nucleus, preoptic periventricular nucleus, and arcuate nucleus (ARC) [9,10,11]. The ARC contains a high density of orexigenic neuropeptide Y (NPY) and agouti-related. Molecules 2018, 23, 3071 peptide (AgRP) co-expressing neurons, as well as anorexigenic proopiomelanocortin (POMC). Cocaine- and amphetamine-regulated transcript (CART) peptide co-expressing neurons [12]. NPY/AgRP neurons and POMC/CART peptide neurons from ARC project to the lateral hypothalamus, modulating orexin containing neurons which increase food intake, and to the paraventricular nucleus (PVN), modulating corticotrophin releasing hormone (CRH) neurons which decrease feeding [12]

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