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, 9 (1), 17373

Higher Body Mass Index Is Linked to Altered Hypothalamic Microstructure

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Higher Body Mass Index Is Linked to Altered Hypothalamic Microstructure

K Thomas et al. Sci Rep.

Abstract

Animal studies suggest that obesity-related diets induce structural changes in the hypothalamus, a key brain area involved in energy homeostasis. Whether this translates to humans is however largely unknown. Using a novel multimodal approach with manual segmentation, we here show that a higher body mass index (BMI) selectively predicted higher proton diffusivity within the hypothalamus, indicative of compromised microstructure in the underlying tissue, in a well-characterized population-based cohort (n1 = 338, 48% females, age 21-78 years, BMI 18-43 kg/m²). Results were independent from confounders and confirmed in another independent sample (n2 = 236). In addition, while hypothalamic volume was not associated with obesity, we identified a sexual dimorphism and larger hypothalamic volumes in the left compared to the right hemisphere. Using two large samples of the general population, we showed that a higher BMI specifically relates to altered microstructure in the hypothalamus, independent from confounders such as age, sex and obesity-associated co-morbidities. This points to persisting microstructural changes in a key regulatory area of energy homeostasis occurring with excessive weight. Our findings may help to better understand the pathomechanisms of obesity and other eating-related disorders.

Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
The hypothalamus on multimodal MRI. (A) The bilateral hypothalamus (right: red, left: orange) of a representative participant according to semi-automated segmentation on anatomical images. (B) Coregistration of the T1-weighted (T1w)-derived hypothalamus mask to the mean diffusivity (MD) image derived by diffusion-weighted imaging. Note the sparing of hypothalamus voxels which are affected by partial volume effects on the MD image (arrows). Images are shown in radiological convention.
Figure 2
Figure 2
Sex differences in hypothalamic volume. Analysis of hypothalamic volume reveals bigger values for male than for female participants (p < 0.001).
Figure 3
Figure 3
Obesity and hypothalamic microstructure. Higher body mass index (BMI) significantly predicts higher hypothalamic mean diffusivity (MD), commonly interpreted as less intact cellular microstructure, in a first (A, n1 = 311, comparison to age, sex-corrected model, F1,306 = 7.1, p = 0.008) and a second independent sample (B, n2 = 236, comparison to age, sex-corrected model, F1,232 = 4.2, p = 0.041). Line indicates regression fit with 95% confidence interval.
Figure 4
Figure 4
Multi-atlas fusion segmentation for automated hypothalamus segmentation. (A) In the registration step both atlas and target images were non-linearly registered to a template image. In this common space another non-linear registration of atlas images to the target image was performed. (B) In the label propagation step all transformations were concatenated and the atlas hypothalami were brought into the native space of the target image (upper images show different label propagations for the same target subject, yellow: propagated label, red: manual label, orange: overlap). Fusion of the region of interest was performed using STEPS (lower image, yellow: fused label, red: manual label, orange: overlap see text for details).
Figure 5
Figure 5
Flowchart of the study illustrating the exclusion criteria, the subsample sizes and the different approaches of data analysis.

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