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

FERNANDEZ G., CORNEJO P., DE FRANCESCO P.N., GARCIA ROMERO G., CABRAL A., PERELLO M.

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 via its specific receptor. In plasma, a des-octanoylated form of ghrelin, named des-acyl ghrelin (DAG), also exists. Many 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 ghrelin receptor independent manner. Since thecells labeled by a DAG fluorescent tracer include the ARC neuropeptide Y (NPY) neurons that regulate food intake, we tested the effect of centrally administered DAG on food intake. We found that DAG failed to affect food intake in ad libitum fed mice; however, it impaired the orexigenic actions of peripherally administered ghrelin. Thus, we conclude that DAG directly targets ARC NPY neurons and antagonizes the orexigenic effects of peripheral ghrelin.