Deciphering the association between morphological differences in hypothalamic subregions and circulating ghrelin and leptin concentrations: exploratory evidence in anorexia nervosa and obesity

Abstract

The hypothalamus, a central regulator of hunger and metabolism, contains subnuclei responsive to peripheral signals such as leptin and ghrelin, which may be altered in anorexia nervosa (AN) and obesity (OB). This exploratory study employed an advanced neuroimaging tool to segment specific hypothalamic subregions in 127 adult women: 24 with AN, 26 with obesity without eating disorders (OB-ED), 26 with obesity and eating disorders (OB + ED), and 51 healthy controls (HC). Participants underwent clinical assessments, fasting blood samples, and T1-weighted 3-Tesla MRI scans. The AN group showed reduced volumes in the total hypothalamus, as well as in the posterior and inferior tuberal subregions, compared to HC, which remained significant after adjusting for total brain volume (TBV). The OB + ED displayed increased volumes in the inferior tuberal and anterior-inferior subregions compared to the HC and OB-ED groups, but differences did not persist after TBV adjustment. In AN, anterior hypothalamic subregions were negatively correlated with leptin concentrations. In contrast, in OB-ED, the same subregions, along with the superior tuberal hypothalamus, showed a positive association with body mass index (BMI). Additionally, an earlier onset of AN correlated with decreased volumes of several hypothalamic subregions, whereas in OB + ED, disorder duration was positively associated with the anterior-superior subregion. Alterations in the volumes of specific hypothalamic subnuclei may serve as clinical indicators of both the severity of obesity (i.e., BMI) and the onset and duration of eating disorders. Although preliminary, these findings contribute to our understanding of the neurobiological mechanisms involved in extreme eating and weight conditions.