Circulating ghrelin regulates GABA neurons of the area postrema, which are required for ghrelin-induced gastric emptying

CABRAL A., CORNEJO P., FERNANDEZ G., DE FRANCESCO P.N., GARCIA ROMERO G., URIARTE M., ZIGMAN J., PORTIANSKY E., REYNALDO M., PERELLO M

ENDOCRINOLOGY

ENDOCRINE SOC

Año: 2017

0013-7227

Ghrelin is known to act on the area postrema (AP), a sensory circumventricular organ located in the medulla oblongata that regulates a variety of important physiological functions.However, the neuronal targets of ghrelin in the AP and their potential role are currently unknown. Here, we used wild-type and genetically modified mice to get insights into the neurons of the AP expressing the ghrelin receptor (GHSR) and their physiological relevance. We show that circulating ghrelin accesses the AP but not other regions of the dorsal vagal complex, which include the nucleus of the solitary tract and the dorsal motor nucleus of the vagus nerve. Also,we show that peripheral administration of ghrelin and fasting induce an increase of c-Fos, a marker of neuronal activation, in GHSR-expressing neurons of the AP, and that GHSR expression is necessary for the fasting-induced activation of AP neurons. In addition, we show that ghrelin sensitive neurons of the AP are mainly GABAergic, and that an intact AP is required for ghrelin-induced gastric emptying. Overall, we show that the capacity of circulating ghrelin toacutely induce gastric emptying in mice requires the integrity of the AP, which contains a population of GABA neurons that are a key target of plasma ghrelin.