Ghrelin deficiency sex-dependently affects food intake, locomotor activity, and adipose and hepatic gene expression in a binge-eating mouse model.

Binge-eating disorder is the most prevalent eating disorder diagnosed, affecting three times more women than men. Ghrelin stimulates appetite and reward signaling, and loss of its receptor reduces binge-eating behavior in male mice. Here, we examined the influence of ghrelin itself on binge-eating behavior in both male and female mice. 5-week-old wild-type (WT) and ghrelin-deficient (Ghrl-/‑ ) mice were housed individually in indirect calorimetry cages for 9 weeks. Binge-like eating was induced by giving mice ad libitum chow, but 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). All groups of BE mice showed binge-eating behavior, eating up to 60% of their 24h intake during the WD access period. Subsequent dark phase chow intake was decreased in Ghrl-/- mice and remained decreased in Ghrl-/- females on non-binge days. Also, non-binge day locomotor activity was lower in Ghrl-/- than WT BE females. Upon sacrifice, Ghrl-/- BE mice weighed less and had a lower lean body mass percentage than WT BE mice. In BE and CW groups, ghrelin and sex altered the expression of genes involved in lipid processing, thermogenesis, and aging in white adipose tissue and livers. We conclude that, although ghrelin deficiency does not hamper the development of binge-like eating, it sex-dependently alters food intake timing, locomotor activity, and metabolism. These results add to the growing body of evidence that ghrelin signaling is sexually dimorphic.