High fat intake in a mouse binge eating model may involve constitutive ghrelin receptor signaling

CORNEJO MP; DE FRANCESCO PN; REYNALDO M; VALDIVIA S; ANDREOLI MF; RAMOS G; GARCÍA ROMERO G; LAZZARINO G; PERELLO M

Buenos Aires

Congreso; II Congress of The Federation of Neuroscience Societies in Latin America, the Caribbean and the Iberian Peninsula; 2016

A variety of human eating disorders display binge eating events, which involve the consumption of large amounts of food in a discrete period of time. Ghrelin is the only peptide hormone known to increase food intake, and its receptor (GHSR) is a G-protein coupled receptor capable of signal in a ghrelin-independent manner. The central distribution of GHSR indicates that ghrelin system regulates both homeostatic and hedonic aspects of feeding. Using a simple model of binge eating, in which ad libitum fed mice are exposed to high fat diet (HFD) four consecutive days for 2 h/day, we have shown that mice develop a high fat intake escalation over the successive events that involve both the activation of the mesolimbic system and the ghrelin signaling. Here, we tested if ghrelin-evoked GHSR signaling is required for the high fat intake escalation in mice and we found that the pharmacologic blockage of ghrelin signaling with a GHSR antagonist failed to affect high fat intake escalation. Interestingly, mice eating HFD 2 h/day by four successive days display an increase of GHSR levels in the ventral tegmental area (VTA), a key component of the mesolimbic pathway, as well as an increase of the c-Fos levels in the dopaminergic neurons of the VTA and one of their main targets: the nucleus accumbens. Unexpectedly, we found that mice with GHSR expression limited to the dopaminergic neurons of the VTA failed to show high fat intake escalation. Thus, we conclude that food intake escalation in mice daily exposed to HFD involves ghrelin-independent GHSR signaling in a subset of neurons different from the dopaminergic neurons of the VTA. Supported by PICTO 2013-0065.