Endocrine Abstracts

Binge-eating disorder is the most prevalent eating disorder diagnosed, affecting three times more women than men. It is characterised by binge-eating episodes: the rapid consumption of a large amount of food, without needing the calories. The gut hormone ghrelin stimulates appetite and reward signalling, and loss of its receptor reduces binge-eating behaviour in male mice. We aimed to examine the influence of ghrelin itself on binge-eating behaviour in mice of both sexes. 5-week-old wild-type (WT) and ghrelin-deficient (GKO) mice were housed individually in an indirect calorimetry system for 9 weeks. Binge-like eating in mice given ad libitum chow was induced by time-restricted access to Western-style diet (WD; 2h access, 3 days/week) in the light phase (BE); control groups received ad libitum chow (CO), or ad libitum access to both diets (CW). Food intake, locomotor activity, body composition, and white adipose tissue (WAT) gene expression were assessed. All groups of BE mice showed binge-eating behaviour, eating up to 60% of their 24h intake during the WD access period. Subsequent dark phase chow intake was decreased by 12.4% in GKO mice (P=0.029) and remained similarly decreased, especially in GKO females, on non-binge days (P=0.015). As a result, on binge days, chow comprised a smaller portion of the 24h caloric intake of GKO BE (48±4%) compared with WT mice (60±2%;P=0.02). This reduction in chow preference was also observed in CW mice (GKO: 3±1%; WT: 8±2%;P=0.029). Compared to males on the same diet, dark phase locomotor activity was increased by 97.6% in CO females (P<0.0001), 107.0% in CW females (P<0.0001), and, on binge days, by 46.0% in BE females (P=0.003). Interestingly, on non-binge days, locomotor activity remained increased in WT females but was reduced to the level of the males in GKO females (interaction:P=0.03). Upon sacrifice, GKO BE mice weighed 7.8% less (P=0.001) and had a 2.2% lower lean body mass percentage than WT BE mice (P=0.014). In inguinal white adipose tissue of BE and CW groups, ghrelin deficiency and female sex were associated with suppression of macrophage polarization-regulatory genes, and increased expression of genes that modulate thermogenesis. We conclude that, in contrast to ghrelin receptor deficiency, ghrelin deficiency does not hamper the development of binge-like eating. Moreover, ghrelin deficiency sex-dependently alters food intake timing, locomotor activity, and inguinal white adipose tissue function. These results add to the growing body of evidence that ghrelin signalling is sexually dimorphic.