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

• Published in: PloS one Vol. 9; no. 5; p. 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: Journal Article
• Language: English
• Published: United States Public Library of Science 22.05.2014; Public Library of Science (PLoS)
• 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; Serbia; Netherlands; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0098180

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.