Structural alterations of individual hypothalamic nuclei in young females with obesity and anorexia nervosa: an in vivo 7-T MRI study

Am J Clin Nutr. 2025 Mar 20:S0002-9165(25)00071-1. doi: 10.1016/j.ajcnut.2025.02.003. Online ahead of print.

ABSTRACT

BACKGROUND: The hypothalamus (HT) plays a crucial role in regulating eating behaviors. Disruptions in its function have been linked to the development of weight-related disorders. Nevertheless, its characterization remains a challenge.

OBJECTIVES: We assessed the structural alterations of individual HT nuclei related to eating behaviors in patients with weight-related disorders, and their association with body mass index (BMI) and severity of eating disorders.

METHODS: Forty-four young females with normal weight (HC, n = 21), restrictive anorexia nervosa (AN, n = 13), and living with obesity (OB, n = 10) were explored in vivo using 7-T high-resolution (0.6 mm isotropic voxel) T₁ quantitative magnetic resonance imaging (MRI). Volumes and quantitative T₁ values of individual HT nuclei were compared after whole-brain normalization using nonparametric tests (corrected for multiple comparisons for groups and regions). We investigated the parameters associated with BMI and eating disorders, such as MRI parameters of HT nuclei, ghrelin and leptin levels, depression, and anxiety using multivariate nonlinear partial least square (NIPALS).

RESULTS: Both AN and OB showed higher volumes of HT relative to HC (Zscores: 0.78 ± 1.06; 1.43 ± 1.51). AN showed significantly higher volumes and T₁ values of the right paraventricular nucleus (PaVN) (volume Zscore: 1.82 ± 1.45; T₁ Zscore: 3.76 ± 4.67), and higher T₁ values of the left PaVN (Zscore: 2.25 ± 2.37) and right periventricular nuclei (Zscore: 3.73 ± 4.81). NIPALS models showed that lower BMI in AN was associated with structural alterations of the bilateral PaVN, right anterior commissure, and left fornix (FX). Higher BMI in OB was associated with structural alterations within the right PaVN, bilateral FX, left posterior hypothalamic nucleus, right lateral HT, and right anterior hypothalamic area. Finally, the severity of eating disorders was associated with larger structural alterations within the bilateral PaVN, bilateral arcuate hypothalamic nuclei, right bed nucleus of stria terminalis, left medial preoptic nucleus, and right tubero-mammillary hypothalamic nucleus.

CONCLUSIONS: Weight-related disorders are associated with significant micro and macrostructural alterations in HT nuclei involved in eating behaviors.

PMID:40128134 | DOI:10.1016/j.ajcnut.2025.02.003