Unacylated ghrelin suppresses ghrelin-induced neuronal activity in the hypothalamus and brainstem of male rats [corrected]

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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Bibliographic Details
Published in:PloS one 2014-05, Vol.9 (5), p.e98180-e98180
Main Authors: 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
Format: Article
Language:English
Subjects:
Acylation
Animals
Base Sequence
Biology and Life Sciences
Brain stem
Brain Stem - drug effects
c-Fos protein
DNA Primers
Endocrinology
Energy
Energy balance
Energy intake
Feeding Behavior - drug effects
Food
Food intake
Gene expression
Gene Expression Profiling
Ghrelin
Ghrelin - administration & dosage
Ghrelin - pharmacology
Growth hormone
Growth hormones
Homeostasis
Hypothalamus
Hypothalamus - drug effects
Internal medicine
Intracerebroventricular administration
Male
Medicine
Medicine and Health Sciences
Melanocortin
Melanocortin MC4 receptors
Mice
Mitochondrial uncoupling protein 2
Modulation
Neural networks
Neurons
Neurons - drug effects
Neuropeptides
Neurosciences
Peptides
Physiology
Polymerase Chain Reaction
Proopiomelanocortin
Rats
Rats, Wistar
Rodents
Signaling
Solitary tract nucleus
Thermogenesis
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Summary: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.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0098180