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Unacylated Ghrelin Suppresses Ghrelin-Induced Neuronal Activity in the Hypothalamus and Brainstem of Male Rats

Ghrelin, the endogenous growth hormone secretagogue, has an important role in metabolic homeostasis. It exists in two major molecular forms: acylated (AG) and unacylated (UAG). Many studies suggest different roles for these two forms of ghrelin in energy balance regulation. In the present study, we...

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Autores principales: Stevanovic, Darko M., Grefhorst, Aldo, Themmen, Axel P. N., Popovic, Vera, Holstege, Joan, Haasdijk, Elize, Trajkovic, Vladimir, van der Lely, Aart-Jan, Delhanty, Patric J. D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031147/
https://www.ncbi.nlm.nih.gov/pubmed/24852945
http://dx.doi.org/10.1371/journal.pone.0098180
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author Stevanovic, Darko M.
Grefhorst, Aldo
Themmen, Axel P. N.
Popovic, Vera
Holstege, Joan
Haasdijk, Elize
Trajkovic, Vladimir
van der Lely, Aart-Jan
Delhanty, Patric J. D.
author_facet Stevanovic, Darko M.
Grefhorst, Aldo
Themmen, Axel P. N.
Popovic, Vera
Holstege, Joan
Haasdijk, Elize
Trajkovic, Vladimir
van der Lely, Aart-Jan
Delhanty, Patric J. D.
author_sort Stevanovic, Darko M.
collection PubMed
description Ghrelin, the endogenous growth hormone secretagogue, has an important role in metabolic homeostasis. It exists in two major molecular forms: acylated (AG) and unacylated (UAG). Many studies suggest different roles for these two forms of ghrelin in energy balance regulation. In the present study, we compared the effects of acute intracerebroventricular administration of AG, UAG and their combination (AG+UAG) to young adult Wistar rats on food intake and central melanocortin system modulation. Although UAG did not affect food intake it significantly increased the number of c-Fos positive neurons in the arcuate (ARC), paraventricular (PVN) and solitary tract (NTS) nuclei. In contrast, UAG suppressed AG-induced neuronal activity in PVN and NTS. Central UAG also modulated hypothalamic expression of Mc4r and Bmp8b, which were increased and Mc3r, Pomc, Agrp and Ucp2, which were decreased. Finally, UAG, AG and combination treatments caused activation of c-Fos in POMC expressing neurons in the arcuate, substantiating a physiologic effect of these peptides on the central melanocortin system. Together, these results demonstrate that UAG can act directly to increase neuronal activity in the hypothalamus and is able to counteract AG-induced neuronal activity in the PVN and NTS. UAG also modulates expression of members of the melanocortin signaling system in the hypothalamus. In the absence of an effect on energy intake, these findings indicate that UAG could affect energy homeostasis by modulation of the central melanocortin system.
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spelling pubmed-40311472014-05-28 Unacylated Ghrelin Suppresses Ghrelin-Induced Neuronal Activity in the Hypothalamus and Brainstem of Male Rats Stevanovic, Darko M. Grefhorst, Aldo Themmen, Axel P. N. Popovic, Vera Holstege, Joan Haasdijk, Elize Trajkovic, Vladimir van der Lely, Aart-Jan Delhanty, Patric J. D. PLoS One Research Article Ghrelin, the endogenous growth hormone secretagogue, has an important role in metabolic homeostasis. It exists in two major molecular forms: acylated (AG) and unacylated (UAG). Many studies suggest different roles for these two forms of ghrelin in energy balance regulation. In the present study, we compared the effects of acute intracerebroventricular administration of AG, UAG and their combination (AG+UAG) to young adult Wistar rats on food intake and central melanocortin system modulation. Although UAG did not affect food intake it significantly increased the number of c-Fos positive neurons in the arcuate (ARC), paraventricular (PVN) and solitary tract (NTS) nuclei. In contrast, UAG suppressed AG-induced neuronal activity in PVN and NTS. Central UAG also modulated hypothalamic expression of Mc4r and Bmp8b, which were increased and Mc3r, Pomc, Agrp and Ucp2, which were decreased. Finally, UAG, AG and combination treatments caused activation of c-Fos in POMC expressing neurons in the arcuate, substantiating a physiologic effect of these peptides on the central melanocortin system. Together, these results demonstrate that UAG can act directly to increase neuronal activity in the hypothalamus and is able to counteract AG-induced neuronal activity in the PVN and NTS. UAG also modulates expression of members of the melanocortin signaling system in the hypothalamus. In the absence of an effect on energy intake, these findings indicate that UAG could affect energy homeostasis by modulation of the central melanocortin system. Public Library of Science 2014-05-22 /pmc/articles/PMC4031147/ /pubmed/24852945 http://dx.doi.org/10.1371/journal.pone.0098180 Text en © 2014 Stevanovic et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Stevanovic, Darko M.
Grefhorst, Aldo
Themmen, Axel P. N.
Popovic, Vera
Holstege, Joan
Haasdijk, Elize
Trajkovic, Vladimir
van der Lely, Aart-Jan
Delhanty, Patric J. D.
Unacylated Ghrelin Suppresses Ghrelin-Induced Neuronal Activity in the Hypothalamus and Brainstem of Male Rats
title Unacylated Ghrelin Suppresses Ghrelin-Induced Neuronal Activity in the Hypothalamus and Brainstem of Male Rats
title_full Unacylated Ghrelin Suppresses Ghrelin-Induced Neuronal Activity in the Hypothalamus and Brainstem of Male Rats
title_fullStr Unacylated Ghrelin Suppresses Ghrelin-Induced Neuronal Activity in the Hypothalamus and Brainstem of Male Rats
title_full_unstemmed Unacylated Ghrelin Suppresses Ghrelin-Induced Neuronal Activity in the Hypothalamus and Brainstem of Male Rats
title_short Unacylated Ghrelin Suppresses Ghrelin-Induced Neuronal Activity in the Hypothalamus and Brainstem of Male Rats
title_sort unacylated ghrelin suppresses ghrelin-induced neuronal activity in the hypothalamus and brainstem of male rats
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4031147/
https://www.ncbi.nlm.nih.gov/pubmed/24852945
http://dx.doi.org/10.1371/journal.pone.0098180
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