Investigating Obesity-associated Brain Inflammation Using Quantitative Water Content Mapping

There is growing evidence that obesity is associated with inflammation in the brain, which could contribute to the pathogenesis of obesity. In humans, it is challenging to detect brain inflammation in vivo. Recently, quantitative magnetic resonance imaging (qMRI) has emerged as a tool for characterising pathophysiological processes in the brain with reliable and reproducible measures. Proton density imaging provides quantitative assessment of the brain water content, which is affected in different pathologies, including inflammation. We enrolled 115 normal weight, overweight and obese men and women (body mass index [BMI] range 20.1-39.7 kg m , age range 20-75 years, 60% men) to acquire cerebral water content mapping in vivo using MRI at 3 Tesla. We investigated potential associations between brain water content with anthropometric measures of obesity, body fat distribution and whole-body metabolism. No global changes in water content were associated with obesity. However, higher water content values in the cerebellum, limbic lobe and sub-lobular region were detected in participants with higher BMI, independent of age. More specifically, the dorsal striatum, hypothalamus, thalamus, fornix, anterior limb of the internal capsule and posterior thalamic radiation showed the strongest relationship with BMI, independent of age. In a subgroup with available measurements (n = 50), we identified visceral adipose tissue to be the strongest tested link between higher water content values and obesity. Individuals with metabolic syndrome had the highest water content values in the hypothalamus and the fornix. There is accumulating evidence that inflammation of the hypothalamus contributed to obesity-associated insulin resistance in that area. Whether brain inflammation is a cause or consequence of obesity in humans still needs to be investigated using a longitudinal study design. Using qMRI, we were able to detect marked water content changes in young and older obese adults, which is most likely the result of chronic low-grade inflammation.