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 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.
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands; Institute of Medical Physiology, School of Medicine, University of Belgrade, Belgrade, Serbia.
Darko M
DM
Stevanovic
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Aldo
A
Grefhorst
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Axel P N
AP
Themmen
Institute of Endocrinology, Diabetes and Diseases of Metabolism, School of Medicine, University of Belgrade, Belgrade, Serbia.
Vera
V
Popovic
Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Joan
J
Holstege
Department of Neuroscience, Erasmus Medical Center, Rotterdam, The Netherlands.
Elize
E
Haasdijk
Institute of Microbiology and Immunology, School of Medicine, University of Belgrade, Belgrade, Serbia.
Vladimir
V
Trajkovic
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Aart-Jan
AJ
van der Lely
Department of Internal Medicine, Erasmus Medical Center, Rotterdam, The Netherlands.
Patric J D
PJ
Delhanty
D000215:Acylation; D000818:Animals; D001483:Base Sequence; D001933:Brain Stem / Q000187:drug effects*; D017931:DNA Primers; D005247:Feeding Behavior / Q000187:drug effects; D020869:Gene Expression Profiling; D054439:Ghrelin / Q000008:administration & dosage / Q000494:pharmacology*; D007031:Hypothalamus / Q000187:drug effects*; D008297:Male; D051379:Mice; D009474:Neurons / Q000187:drug effects*; D016133:Polymerase Chain Reaction; D017208:Rats, Wistar
D017931:DNA Primers; D054439:Ghrelin