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

Abstract

Ghrelin, an orexigenic hormone released from the empty stomach, provides a gutbrain signal that promotes many appetitive behaviours, including anticipatory and goaldirected 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. K E Y W O R D Sbinge eating, dietary preference, food choice, ghrelin, GHS-R1A, high-fat diet

Activation of amylin receptors attenuates alcohol‐mediated behaviours in rodents

“…Given that the mice used in our experiments were satiated, our results are in accordance with studies showing that ghrelin does not increase palatable food intake in ad libitum fed mice, but it does so in fasted mice (Alen et al 2013). This is corroborated by our previous data presenting that ghrelin does not increase peanut butter intake in satiated mice (Kalafateli et al 2017) and that its administration in rats scheduled for palatable feeding decreases high-fat-diet consumption and enhances normal chow intake (Schéle et al 2016;Bake, Hellgren, & Dickson 2017). It is therefore possible that the amylinergic mechanisms regulating food reward do not coincide with the ones mediating substance reinforcement.…”

Growth hormone secretagogue receptor signalling affects high‐fat intake independently of plasma levels of ghrelin andLEAP2, in a 4‐day binge eating model

“…For example, a recent study found that i.c.v.-injected ghrelin shifts diet preference, increasing RC intake and reducing HF intake, in rats exposed to a 2-week binge eating protocol with simultaneous access to both diets. 58 Also, it was shown that rats intermittently and time-limited fed with different palatable diets for several weeks displayed higher plasma ghrelin levels before each binge eating event. [59][60][61][62][63] In particular, one study found that increments of plasma ghrelin levels positively correlated with food anticipatory activity and that a GHSR antagonist decreased such behaviour, 60 whereas another study showed that blockade of plasma ghrelin increments attenuated the magnitude of binge-like HF intake.…”

“…Importantly, GHSR signalling may play different roles in animals exposed to binge eating protocols for longer periods of time, when changes in body weight become evident. For example, a recent study found that i.c.v.‐injected ghrelin shifts diet preference, increasing RC intake and reducing HF intake, in rats exposed to a 2‐week binge eating protocol with simultaneous access to both diets . Also, it was shown that rats intermittently and time‐limited fed with different palatable diets for several weeks displayed higher plasma ghrelin levels before each binge eating event .…”

Ghrelin's effects on food motivation in rats are not limited to palatable foods

“…Considering the involvement of ghrelin in food reward and food motivation for palatable food, it is interesting that, when a food choice consisting of chow, lard and sucrose pellets is offered, acute delivery of ghrelin mainly induces a preference change towards chow . Moreover, in a scheduled‐feeding paradigm, when animals are bingeing on a high‐fat diet, acute delivery of ghrelin can change the food preference during the binge from a high‐fat diet to chow . Such work inspired the present study, which investigates whether ghrelin is also able to increase the motivation for healthier (less palatable) foods such as chow, even in satiated rats.…”