Neuroendocrinology and Neuroimmunology
Author: Franco Barrile | Email: francobarrile@gmail.com
Franco Barrile 1°, Frederick Wasinsiki 3°, María Paula Cornejo 1°, Jose Donato Jr 2°, Mario Perelló 1°
1° Instituto Multidisciplinario de Biología Celular (IMBICE)
2° Universidad de São Paulo (USP)
3° Universidad Federal de São Paulo (UNIFESP)
The neuroendocrine mechanisms that regulate food intake are only partially known, despite such behaviour is essential for survival. Ghrelin and growth hormone (GH) are two orexigenic hormones that act via growth hormone secretagogue receptor (GHSR) and GH receptor (GHR) respectively. In mice, both hormones increase food intake by acting on the AgRP/NPY neurons of the hypothalamic arcuate nucleus (ARH) and their actions seems to crosstalk. Recently, we reported that mice with genetic ablation of GHR specifically in neurons fail to increase food intake in response to ghrelin. Since the genetic ablation of GHR also affects neural circuit connectivity, we take advantage of the well-characterize GHR antagonist pegvisomant to test if the acute pharmacological blockage of GHR affects ghrelin-induced food intake in mice. We found that pegvisomant (4 mg/Kg, ip) decreases acute food intake in wild-type, but not in GHR-knock out, mice as well as NPY gene expression in the ARH. Also, we found that pegvisomant treatment abrogates the orexigenic effects of systemically injected ghrelin (0.2 mg/kg) but does affect the ghrelin-induced increase of c-Fos in the ARH. Thus, pharmacological blockage of GHR signalling in mice reduces ad libitum and ghrelin-induced food intake via a mechanism that may involve NPY expression in the ARH.