Binge-eating disorder (BED) is the most prevalent eating disorder diagnosed, affecting more women than men. It is characterised by binge-eating episodes: rapid consumption of large amounts of food, regardless of caloric need. Ghrelin stimulates both appetite and reward signalling, and loss of its receptor, GHSR1a, reduces binge-eating behaviour in mice. Our aim was to examine the influence of ghrelin itself in a mouse model of binge-eating.

Male and female mice (5 weeks old) were housed individually in an indirect calorimetry system. Binge-like eating was induced by giving mice ad libitum chow, but time-restricted access to a Western-style diet (WD; 2h access, 3 days/week) in the light phase (B); control groups either received ad libitum chow (C), or ad libitum access to both diets (W). Food intake, body composition and white adipose tissue (WAT) gene expression were assessed.

On binge days, B mice ate up to 60% of their 24h caloric intake during the 2h WD access period. Subsequent dark phase chow intake was decreased in GKO males, whereas 24h chow intake was decreased in GKO females on non-binge days. As a result, on binge days, WD comprised a larger proportion of the 24h caloric intake of GKO B mice than WT B mice. This preference for WD was also seen in GKO W mice. Upon sacrifice, GKO B mice weighed less and had a lower lean body mass percentage than WT B mice. In C mice, body composition showed a genotype-sex interaction effect: GKO females had 3.1% more fat than in WT females, while there was no genotype effect in males. Glucose tolerance was improved in GKO males compared to WT males in the C and W groups, but no such effect was seen in the B group. Expression of genes involved in lipid processing, thermogenesis, and aging was regulated by genotype and sex in inguinal WAT and in liver.

In conclusion, these results suggest that ghrelin deficiency sex-dependently alters food intake, glucose homeostasis, and adipose and hepatic gene expression. These results add to the growing body of evidence that ghrelin signalling is sexually dimorphic.