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

Abstract

Ghrelin, an orexigenic hormone released from the empty stomach, provides a gut-brain signal that promotes many appetitive behaviors, including anticipatory and goal-directed behaviors for palatable treats high in sugar and/or fat. Here we sought to determine whether ghrelin is able to influence and/or may even have a role in binge-like behavior in rodents. To this end, we used a palatable scheduled feeding (PSF) paradigm in which ad libitum chow-fed rodents are trained to "binge" on high fat diet (HFD) offered each day for a limited period of 2 hr. After 2 weeks of habituation to this paradigm, on the test day and immediately prior to the 2 hr PSF, rats were administered ghrelin or vehicle solution by the intracerebroventricular (ICV) route. Remarkably and unexpectedly, during the palatable scheduled feed, when rats normally only binge on the HFD, those injected with ICV ghrelin started to eat more chow and chow intake remained above baseline for the rest of the 24 hr day. We identify the VTA (a key brain area involved in food reward) as a substrate involved as 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 behavior 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 similar manner as WT mice suggesting that ghrelin signalling may not have a critical role in 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), effects that were somewhat divergent from fasting.

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