Hypothalamic subregion alterations in anorexia nervosa and obesity: Association with appetite‐regulating hormone levels

Abstract Objective Anorexia nervosa (AN) and obesity are weight‐related disorders with imbalances in energy homeostasis that may be due to hormonal dysregulation. Given the importance of the hypothalamus in hormonal regulation, we aimed to identify morphometric alterations to hypothalamic subregions linked to these conditions and their connection to appetite‐regulating hormones. Methods Structural magnetic resonance imaging (MRI) was obtained from 78 patients with AN, 27 individuals with obesity and 100 normal‐weight healthy controls. Leptin, ghrelin, and insulin blood levels were measured in a subsample of each group. An automated segmentation method was used to segment the hypothalamus and its subregions. Volumes of the hypothalamus and its subregions were compared between groups, and correlational analysis was employed to assess the relationship between morphometric measurements and appetite‐regulating hormone levels. Results While accounting for total brain volume, patients with AN displayed a smaller volume in the inferior‐tubular subregion (ITS). Conversely, obesity was associated with a larger volume in the anterior‐superior, ITS, posterior subregions (PS), and entire hypothalamus. There were no significant volumetric differences between AN subtypes. Leptin correlated positively with PS volume, whereas ghrelin correlated negatively with the whole hypothalamus volume in the entire cohort. However, appetite‐regulating hormone levels did not mediate the effects of body mass index on volumetric measures. Conclusion Our results indicate the importance of regional structural hypothalamic alterations in AN and obesity, extending beyond global changes to brain volume. Furthermore, these alterations may be linked to changes in hormonal appetite regulation. However, given the small sample size in our correlation analysis, further analyses in a larger sample size are warranted. Public Significance Using an automated segmentation method to investigate morphometric alterations of hypothalamic subregions in AN and obesity, this study provides valuable insights into the complex interplay between hypothalamic alterations, hormonal appetite regulation, and body weight, highlighting the need for further research to uncover underlying mechanisms.