DES-ACYL GHRELIN DIRECTLY TARGETS THE ARCUATE NUCLEUS IN A GHRELIN- RECEPTOR INDEPENDENT MANNER AND IMPAIRS THE OREXIGENIC EFFECT OF GHRELIN

GIMENA FERNANDEZ; AGUSTINA CABRAL; MARÍA PAULA CORNEJO; PABLO N. DE FRANCESCO; GUADALUPE GARCÍA ROMERO; MIRTA REYNALDO; MARIO PERELLÓ

JOURNAL OF NEUROENDOCRINOLOGY.

WILEY-BLACKWELL PUBLISHING, INC

Lugar: Londres; Año: 2016

0953-8194

Ghrelin is a stomach-derived octanoylated peptide hormone that plays a variety of well-established biological roles acting via its specific receptor known as growth hormone secretagogue receptor (GHSR). In plasma, a des-octanoylated form of ghrelin, named des-acyl ghrelin (DAG), also exists. Several studies have suggested that DAG is a signaling molecule that has specific targets, including the brain, and regulates some physiological functions. However, no specific receptor for DAG has been reported until now, and, as a consequence, the potential role of DAG as hormone has remained a matter of debate. Here, we show that DAG specifically binds to and acts on a subset of arcuate nucleus (ARC) cells in a GHSR independent manner. ARC cells labeled by a DAG fluorescent tracer include the neuropeptide Y (NPY) and non-NPY neurons. Given the well-established role of the ARC in appetite regulation, we tested the effect of centrally administered 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 of peripherally administered ghrelin. Thus, we conclude that DAG directly targets ARC neurons and antagonizes the orexigenic effects of peripherally administered ghrelin.