Association of Obesity-Mediated Insulin Resistance and Hypothalamic Volumes: Possible Sex Differences

Abstract

The hypothalamus is important in hunger and metabolism. Although a lot is known about the basic role of the human hypothalamus, less is known about how the in vivo volume is affected in obesity, particularly among adolescents. Based on pediatric body mass index percentiles, 95 participants were assigned to lean or obese groups. All subjects had medical evaluations, including fasting blood tests, to assess insulin sensitivity and circulating CRP and neurotrophins (NGF and BDNF) and an MRI of the brain. Hypothalamic volumes were measured by a segmentation method combining manual and automated steps. Overall, obese participants had descriptively smaller hypothalamic volumes, although this difference did not reach statistical significance; however, among obese participants, females had significantly smaller hypothalamic volumes than their male counterparts. There was a significant interaction between insulin resistance and sex on hypothalamus volume; obese females with significant insulin resistance have smaller hypothalamic volumes than obese males. Obese adolescents had higher circulating CRP and neurotrophin levels. Furthermore, among obese females, BDNF concentrations were inversely associated with hypothalamus volumes (r = −0.48). Given this negative association between BDNF and hypothalamus volumes among obese insulin-resistant females, elevated neurotrophin levels may suggest an attempt at protective compensation.

Altered hypothalamic microstructure in human obesity

“…Results of our regression analysis suggested that hypothalamic volumes are higher for males compared to females, irrespective of age and BMI. This finding might be attributable to known sex differences in metabolic dysregulation (Ha, Cohen, Tirsi, & Convit, 2013) and the neuroendocrine regulation system (Chowen, Argente-Arizón, Freire-Regatillo, & Argente, 2018). Furthermore, we found a significant left-right asymmetry in hypothalamic volume with higher volumes for the left than for the right hypothalamus, which is in line with a previous publication that described a trend in the same direction in a sample of 84 subjects (Wolff et al, 2018).…”

Fitness, insulin sensitivity, and frontal lobe integrity in adults with overweight and obesity

“…However, analyses were conducted on the total set of participants. Given that normal aging is associated with increased BMI and fat mass , decreased physical activity levels , and brain tissue loss , and that we have observed differential effects of metabolic impairment on brain by sex , we controlled for age and sex in all analyses. Brain volumes and thicknesses were residualized to ICV using linear regression.…”

Hypothalamic inflammation and gliosis in obesity

“…increased damage) was correlated with increased BMI and impaired cognitive performance. Finally, a few studies of structural alterations in the brains of obese subjects have shown reduced connectivity through the corpus callosum (75, 76), reduced hypothalamic volume in obese females with insulin resistance (77), and greater connectivity between the hypothalamus and reward-related brain areas than homeostatic areas (78•). Together, these data support the hypothesis that humans develop hypothalamic pathology akin to that of rodents with gliosis and injury potentially promoting weight gain, insulin resistance, and cognitive impairment.…”