Investigating ghrelin and its isoforms in eating disorders: a network meta-analysis

Background: Eating disorders (EDs) are serious psychiatric conditions disorders characterized by impairments in appetite regulation and energy balance. Among the biological factors implicated in their pathophysiology, the orexigenic hormone ghrelin and its isoforms (acyl-ghrelin [AG] and desacyl-ghrelin [DAG]) have been shown to play a key role in appetite regulation and may contribute to the maintenance of disordered eating behaviors. Methods: A systematic review of existing literature and meta-analysis were conducted, including 80 studies examining fasting blood levels of ghrelin, AG, and DAG across various ED diagnostic categories and healthy controls (HC), including also individuals with recovered AN (AN-rec). A network meta-analysis (NMA) approach through a multilevel linear mixed-effects meta-regression model was employed to estimate hormone levels, while accounting for covariates such as body mass index (BMI), sex, blood composition and assay type. Results: Ghrelin levels were significantly elevated in individuals with anorexia nervosa (AN) and bulimia nervosa (BN) when compared to HC, while binge eating disorder (BED) was associated with lower ghrelin levels than individuals with BN and HC. AG and DAG levels were significantly elevated in individuals with AN compared to HC, and confirmed higher in AN-rec if compared to HC. No significant differences in ghrelin, AG and DAG levels were observed for avoidant/restrictive food intake disorder (ARFID). Conclusions: This meta-analysis highlighted significant differences in the levels of ghrelin and its isoforms across various ED subgroups and HC, emphasizing their potential roles in the pathophysiology of these disorders, in a perspective of potential targeted therapeutic implications