Background: Obesity is a persistent disorder that almost universally recurs following treatment, suggesting a disruption on central nervous system control over energy homeostasis. Recent literature suggests that hypothalamic inflammation may have an important role on obesity pathogenesis. This inflammatory reaction, which histologically appears as a reactive gliosis, may be detected using magnetic resonance imaging (MRI), and has just been shown in rodent models and adults.
Objective and hypotheses: To test for hypothalamic gliosis in obese children and adolescents using quantitative MRI.
Method: Eleven obese and 9 lean children and adolescents underwent fasting blood draws, body composition analysis by DXA, and brain MRI scans to measure T2 relaxation time using a multi-echo T2 sequence.
Results: Participants mean age was 13.4±2.4 year. Obese children had higher mean BMI z-score (2.1±0.3 vs −0.3±0.9, P<0.001), plasma leptin levels (33.4±15.4 vs 4.9±5.6 pg/ml, P<0.001) and pro-inflammatory cytokines (TNF-α: 2.0±0.7 vs 1.2±0.6 pg/ml, P=0.02; IL-6: 2.9±1.7 vs 1.0±0.5 pg/ml, P=0.004) and lower adiponectin levels (4.4±1.7 vs 6.8±1.5 ng/mL, P=0.005). The groups did not differ in age (P=0.41), sex and pubertal status proportions (chi2=0.20, P=0.66; chi2=0.80, P=0.37, respectively) or in mean fasting insulin concentrations (obese 6.2±3.1 vs lean 6.4±1.6 mcU/ml, P=0.35). Obese subjects had longer T2 relaxation times in the Medial Basal Hypothalamus (MBH) when compared to lean group (105.9±4.2 vs 99.5±4.3 ms), consistent with gliosis. Moreover, there was a highly significant group*region interaction (P=0.0016), demonstrating that signs of gliosis were specific to the MBH as compared to control brain regions. Longer T2 relaxation times were correlated with higher visceral body fat percentage (R2=0.35, P=0.01) and android fat percentage (R2=0.46, P=0.003), but not fasting insulin concentrations (R2=0.02, P=0.6).
Conclusion: Obese children have signs of hypothalamic gliosis that, when present, is associated with body fat distribution signifying high metabolic risk. The presence of MBH gliosis in an obese pediatric population raises concern that hypothalamic inflammation plays a role in childhood obesity and is prior to the development of insulin resistance.
10 - 12 Sep 2016
European Society for Paediatric Endocrinology