Des-Acyl Ghrelin Directly Targets the Arcuate Nucleus in a Ghrelin- Receptor Independent Manner and Impairs the Orexigenic Effect of Ghrelin

G. FERNANDEZ, A. CABRAL, M. P. CORNEJO, P. N. DE FRANCESCO, G. GARCIA-ROMERO, M. REYNALDO AND M. PERELLO; G. FERNANDEZ, A. CABRAL, M. P. CORNEJO, P. N. DE FRANCESCO, G. GARCIA-ROMERO, M. REYNALDO AND M. PERELLO

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Año: 2016

0953-8194

Ghrelin is a stomach-derived octanoylated peptide hormone that plays a variety of well-establishedbiological roles acting via its specific receptor known as growth hormone secretagoguereceptor (GHSR). In plasma, a des-octanoylated form of ghrelin, named des-acyl ghrelin (DAG),also exists. DAG is suggested to be a signalling molecule that has specific targets, including thebrain, and regulates some physiological functions. However, no specific receptor for DAG hasbeen reported until now, and, consequently, the potential role of DAG as a hormone hasremained a matter of debate. In the present study, we show that DAG specifically binds to andacts on a subset of arcuate nucleus (ARC) cells in a GHSR-independent manner. ARC cellslabelled by a DAG fluorescent tracer include the neuropeptide Y (NPY) and non-NPY neurones.Given the well-established role of the ARC in appetite regulation, we tested the effect of centrallyadministered DAG on food intake. We found that DAG failed to affect dark phase feeding,as well as food intake, after a starvation period; however, it impaired the orexigenic actions ofperipherally administered ghrelin. Thus, we conclude that DAG directly targets ARC neuronesand antagonises the orexigenic effects of peripherally administered ghrelin.