Ghrelin-Activating Enzyme Linked to Food Reward and Binge Eating

The hormone ghrelin is widely known as the 'hunger hormone,' playing a crucial role in regulating appetite and metabolism. Its active form, acylated ghrelin, is produced by the enzyme ghrelin O-acyltransferase (GOAT). Dysregulation of this system has been implicated in various eating disorders, including binge eating disorder (BED), characterized by recurrent episodes of consuming unusually large amounts of food with a sense of loss of control. This study aimed to comprehensively investigate the specific roles of ghrelin and the GOAT enzyme in modulating food reward, food motivation, and the underlying mechanisms contributing to binge eating behavior.

Treatment with GOATi-123 significantly attenuated binge-like eating episodes, showing a 43% reduction in the frequency of binge eating compared to vehicle-treated controls (p<0.001). Food reward-seeking behavior, measured by sucrose preference, was also markedly decreased by 35% in the treated group (p<0.01), indicating a reduced hedonic response to palatable food. Furthermore, food motivation, assessed through operant conditioning, demonstrated a 2.8-fold decrease in lever presses for food rewards (p<0.005). Biochemical analysis confirmed that GOATi-123 treatment led to a 60% decrease in circulating acylated ghrelin levels (p<0.001) without significantly altering total ghrelin. > The most important finding was that inhibiting the GOAT enzyme effectively reduced both the incidence of binge eating and the motivational drive for food reward, directly linking acylated ghrelin to these pathological eating behaviors.