Circulating Ghrelin Acts on GABA Neurons of the Area Postrema and Mediates Gastric Emptying in Male Mice

CABRAL, AGUSTINA; CORNEJO, MARÍA P.; FERNANDEZ, GIMENA; DE FRANCESCO, PABLO N.; GARCIA-ROMERO, GUADALUPE; URIARTE, MAIA; ZIGMAN, JEFFREY M.; PORTIANSKY, ENRIQUE; REYNALDO, MIRTA; PERELLO, MARIO

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2017 vol. 158 p. 1436 - 1449

0013-7227

Ghrelin is known to act on the area postrema (AP), a sensory circumventricular organ located in themedulla oblongata that regulates a variety of important physiological functions. However, theneuronal targets of ghrelin in the AP and their potential role are currently unknown. In this study,we used wild-type and genetically modified mice to gain insights into the neurons of the APexpressing the ghrelin receptor [growth hormone secretagogue receptor (GHSR)] and their role. Weshow that circulating ghrelin mainly accesses the AP but not to the adjacent nucleus of the solitarytract. Also, we show that both peripheral administration of ghrelin and fasting induce an increase ofc-Fos, a marker of neuronal activation, in GHSR-expressing neurons of the AP, and that GHSRexpression is necessary for the fasting-induced activation of AP neurons. Additionally, we show thatghrelin-sensitive neurons of the AP are mainly g-aminobutyric acid (GABA)ergic, and that an intactAP is required for ghrelin-induced gastric emptying. Overall, we show that the capacity of circulatingghrelin to acutely induce gastric emptying in mice requires the integrity of the AP, which contains apopulation of GABA neurons that are a target of plasma ghrelin.