Higher body mass index is linked to altered hypothalamic microstructure

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.

Magnetic resonance assessment of the cerebral alterations associated with obesity development

“…To date, contradictory results have been reported concerning the correlations between regional cerebral volumes and obesity. A very recent study 84 reported that BMI was not significantly correlated with hypothalamic volumes, but that additional factors such as sex and laterality did have an actual influence on the size of the hypothalamus. This particular study, performed on two large human cohorts, revealed that men depicted significantly higher hypothalamic volumes than women –irrespective to head size – and that the left lateral lobe of the hypothalamus was bigger than the right.…”

“…A recent and methodologically very well controlled study, performed on two large human cohorts, found a positive correlation between BMI and MD, suggesting hypothalamic microstructural alterations during obesity. 84 Again, the mechanisms underlying the reported changes remained elusive, with a variety of processes being potentially consistent with the observed increases in MD. Indeed, phenomena such as enhanced amount of extracellular fluid accompanying neuronal loss, affected vessel integrity or gliosis, would all result in increased diffusion coefficients, becoming consistent with the reported findings (Figure 3).…”

Automated diffusion-based parcellation of the hypothalamus reveals subunit-specific associations with obesity

“…This approach served to obtain a similar range of Euclidean distances and replaced multiplication of the ODFs by a constant as proposed in the original paper 17 . The optimal number of clusters was evaluated between k = [2,3,4,5,6] as observed in the literature, by minimizing the Davies-Bouldin index 43 in 20 randomly selected participants. The Davies-Bouldin index measures similarity as the ratio of within-cluster to between-cluster distances and is a commonly used method to determine a proper number of clusters.…”

“…For example, research suggests that functional connections between the insula and hypothalamus are related to obesity 1 , 4 , indicating compromised mechanisms of food intake control. Additionally, mean diffusivity (MD), reflecting overall diffusion within the hypothalamus has been associated with obesity, suggesting altered microstructural integrity 5 . Although the hypothalamus is a small structure of about 1–4 cm 3 , it is made up of approximately 15 distinct nuclei 6 with different connections to widespread cortical and subcortical areas 7 .…”

Role of Sirtuins in Modulating Neurodegeneration of the Enteric Nervous System and Central Nervous System

“…Inflammation of the hypothalamus from high fat feeding induces Inhibitor Of Nuclear Factor Kappa-B (IKKβ)/NF-kB-dependent inflammation, changes satiety control, and increases the risk for developing obesity (Timper and Bruning, 2017 ). Magnetic resonance imaging (MRI) has shown an inverse relationship between Body Mass Index (BMI) as well as diabetes and brain volume, neuron viability, and gliosis in the hypothalamus (Thomas et al, 2019 ). Obese individuals with higher BMI with no cognitive defects also displayed decreased gray matter, brain atrophy in the frontal lobe, hippocampus and thalamus when compared to non-obese, thus demonstrating extensive neurodegeneration (Stillman et al, 2017 ).…”