Neuroendocrinology and Neuroimmunology
Author: Lucia Giovanini | email: luciagiovanini5@gmail.com
Lucia Giovanini 1°, María Paula Cornejo 1°, Franco Barrile 1°, Guadalupe Garcia Romero 1°, Antonella Fittipaldi 1°, Daniel Castrogiovanni 1°, Julieta Aguggia 1°, Mario Perello 1
1° IMBICE
Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous ligand of the growth hormone secretagogue receptor (GHSR), a receptor mainly expressed in the brain that is implicated in the regulation of energy balance. In humans and rodents, LEAP2 acts as an antagonist of GHSR blocking the effects of ghrelin, a peptide hormone with orexigenic effect. We aim to study the extent to which LEAP2 reaches the central nervous system. We used mice to examine the presence of LEAP2 in the brain parenchyma and the cerebrospinal fluid (CSF). Using enzyme immunoassays, we found that LEAP2 is present in the CSF of ad libitum fed mice and becomes undetectable in the CSF of fasted mice. Strikingly, we could not detect LEAP2 in the brain parenchyma of satiated mice using immunohistochemistry. Then, we studied the inhibitory effect of LEAP2 on ghrelin-induced food intake. The central administration of LEAP2 blocks the orexigenic effect of peripherally administered ghrelin, this effect last less than 24 hours and diminishes overnight food intake and body weight of mice. We also found that central LEAP2 treatment does not affect the levels of the marker of neuronal activation c-Fos in any brain nuclei. Finally, we found that central injections of LEAP2 block the delayed orexigenic effect of peripherally administered ghrelin. Altogether, our results suggest that LEAP2 reaches the brain via the CSF and that central LEAP2 acutely blocks the orexigenic effect of exogenously administered ghrelin.