Acute ghrelin changes food preference from a high-fat diet to chow during binge-like eating in rodents

Ghrelin, an orexigenic hormone released from the empty stomach, provides a gut-brain signal that promotes many appetitive behaviours, including anticipatory and goal-directed behaviours for palatable treats high in sugar and/or fat. In the present study, we aimed to determine whether ghrelin is able to influence and/or may even have a role in binge-like eating behaviour in rodents. Accordingly, we used a palatable scheduled feeding (PSF) paradigm in which ad lib. chow-fed rodents are trained to 'binge' on a high-fat diet (HFD) offered each day for a limited period of 2 hours. After 2 weeks of habituation to this paradigm, on the test day and immediately prior to the 2-hour PSF, rats were administered ghrelin or vehicle solution by the i.c.v. route. Remarkably and unexpectedly, during the palatable scheduled feed, when rats normally only binge on the HFD, those injected with i.c.v. ghrelin started to eat more chow and chow intake remained above baseline for the rest of the 24-hour day. We identify the ventral tegmental area (VTA) (a key brain area involved in food reward) as a substrate involved because these effects could be reproduced, in part, by intra-VTA delivery of ghrelin. Fasting, which increases endogenous ghrelin, immediately prior to a palatable schedule feed also increased chow intake during/after the schedule feed but, in contrast to ghrelin injection, did not reduce HFD intake. Chronic continuous central ghrelin infusion over several weeks enhanced binge-like behaviour in palatable schedule fed rats. Over a 4-week period, GHS-R1A-KO mice were able to adapt and maintain large meals of HFD in a manner similar to wild-type mice, suggesting that ghrelin signalling may not have a critical role in the acquisition or maintenance in this kind of feeding behaviour. In conclusion, ghrelin appears to act as a modulating factor for binge-like eating behaviour by shifting food preference towards a more nutritious choice (from HFD to chow), with these effects being somewhat divergent from fasting.