Centrally Administered Ghrelin Acutely Influences Food Choice in Rodents.

Erik Schéle,Cristina Rabasa,Suzanne L Dickson,Tina Bake,Miguel López

doi:10.1371/journal.pone.0149456

Abstract

We sought to determine whether the orexigenic hormone, ghrelin, is involved in the intrinsic regulation of food choice in rats. Ghrelin would seem suited to serve such a role given that it signals hunger information from the stomach to brain areas important for feeding control, including the hypothalamus and reward system (e.g. ventral tegmental area, VTA). Thus, in rats offered a choice of palatable foods (sucrose pellets and lard) superimposed on regular chow for 2 weeks, we explored whether acute central delivery of ghrelin (intracerebroventricular (ICV) or intra-VTA) is able to redirect their dietary choice. The major unexpected finding is that, in rats with high baseline lard intake, acute ICV ghrelin injection increased their chow intake over 3-fold, relative to vehicle-injected controls, measured at both 3 hr and 6 hr after injection. Similar effects were observed when ghrelin was delivered to the VTA, thereby identifying the VTA as a likely contributing neurobiological substrate for these effects. We also explored food choice after an overnight fast, when endogenous ghrelin levels are elevated, and found similar effects of dietary choice to those described for ghrelin. These effects of fasting on food choice were suppressed in models of suppressed ghrelin signaling (i.e. peripheral injection of a ghrelin receptor antagonist to rats and ghrelin receptor (GHSR) knock-out mice), implicating a role for endogenous ghrelin in the changes in food choice that occur after an overnight fast. Thus, in line with its role as a gut-brain hunger hormone, ghrelin appears to be able to acutely alter food choice, with notable effects to promote “healthy” chow intake, and identify the VTA as a likely contributing neurobiological substrate for these effects.

Highlights

The neurobiology of food choice remains a less chartered landscape in obesity research, partly reflecting the large number of intrinsic and environmental factors that guide it [1]
This orexigenic effect was still evident at 6 hr post-injection by which time total energy intake was 24 ± 3 kcal for ghrelin treatment compared to 11 ± 1 kcal for vehicle treatment (P
We demonstrate an unexpected effect of acute central injection of ghrelin, an orexigenic and reward-promoting hormone, to cause an acute >3 fold increase in chow intake in rats offered an ad libitum free choice diet comprising two palatable choices superimposed on regular chow

Summary

Introduction

The neurobiology of food choice remains a less chartered landscape in obesity research, partly reflecting the large number of intrinsic and environmental factors that guide it [1]. Ghrelin would seem a good candidate to steer dietary choice given that it appears to signal hunger information from the empty stomach [5] to brain areas important for feeding control, including areas linked to food reward/motivation [6, 7]. Studies in rodents demonstrate that ghrelin is able to orchestrate a number of behavioral responses that extend beyond food intake to include food reward [10], food-anticipatory [11, 12] and food-motivated behaviors [13,14,15]. At the level of the ventral tegmental area (VTA, an area important for reward), ghrelin is able to drive food-motivated behavior and food intake [14, 16], yet we do not know if ghrelin action at this site has consequences for food choice

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