Hypothalamic volume is associated with body mass index

Abstract

The hypothalamus is an important neuroendocrine hub for the control of appetite and satiety. In animal studies it has been established that hypothalamic lesioning or stimulation causes alteration to feeding behaviour and consequently body mass, and exposure to high calorie diets induces hypothalamic inflammation. These findings suggest that alterations in hypothalamic structure and function are both a cause and a consequence of changes to food intake. However, there is limited in vivo human data relating the hypothalamus to obesity or eating disorders, in part due to technical problems relating to its small size. Here, we used a novel automated segmentation algorithm to exploratorily investigate the relationship between hypothalamic volume, normalised to intracranial volume, and body mass index (BMI). The analysis was applied across four independent datasets comprising of young adults (total n = 1,351 participants) spanning a range of BMIs (13.3 - 47.8 kg/m²). We compared underweight (including individuals with anorexia nervosa), healthy weight, overweight and obese individuals in a series of complementary analyses. We report that overall hypothalamic volume is significantly larger in overweight and obese groups of young adults. This was also observed for a number of hypothalamic sub-regions. In the largest dataset (the HCP-Young Adult dataset (n = 1111)) there was a significant relationship between hypothalamic volume and BMI. We suggest that our findings of a positive relationship between hypothalamic volume and BMI is potentially consistent with hypothalamic inflammation as seen in animal models in response to high fat diet, although more research is needed to establish a causal relationship. Overall, we present novel, in vivo findings that link elevated BMI to altered hypothalamic structure. This has important implications for study of the neural mechanisms of obesity in humans.

Keywords: Anorexia nervosa; Body Mass Index (BMI); Hypothalamus; Inflammation; Obesity; Overweight; Structural MRI.

Fig. 1

A Sagittal brain slices showing segmented hypothalamic nuclei B Axial brain slices showing segmented hypothalamic nuclei and whole hypothalamus.

Fig. 2

Anorexia nervosa (AN), bulimia nervosa (BN), eating disorder matched control, overweight, obese and overweight/obese control groups (Control groups = BMI 18.5 – 24.9, overweight = BMI 25 – 29.9, obese = BMI 30 +.): A left anterior-inferior and B right posterior hypothalamic substructures normalised to intracranial volume (ICV). Left anterior-inferior and right posterior hypothalamic nuclei were significantly larger in those with body mass index (BMI) >30 compared to healthy weight controls. (* = p^corr < 0.05).

Fig. 3

Whole hypothalamic volumes (A left and B right) normalised to intracranial volume (ICV) from the HCP-Young Adult dataset. Underweight = BMI < 18.49, normal weight = BMI 18.5 – 24.9, overweight = BMI 25 – 29.9, obese = BMI 30 +. (* = p^corr < 0.05, ** = p^corr < 0.01).

Fig. 4

Right and left whole hypothalamic volumes exhibit a significant positive association with BMI (p < 0.05) (r² = 0.009, 0.012 respectively).