Childhood obesity is linked to putative neuroinflammation in brain white matter, hypothalamus, and striatum

Abstract

Introduction Childhood obesity is increasingly prevalent and confers elevated risk of developing medical complications across the lifespan. Given the brain's prominent involvement in homeostatic and hedonic eating, it is crucial to understand brain health in obesity. Recent studies using quantitative T2-weighted MRI and diffusion-weighted MRI showed obesity-related putative neuroinflammation in human brain. To assess convergent validity across diffusion-based MRI techniques and extend these findings, this study characterized tissue microstructure of white matter (WM) tracts and energy regulation and reward processing brain regions in children across levels of obesity-related measures, using diffusion basis spectrum imaging (DBSI). Methods Using data from the Adolescent Brain Cognitive Development Study (ABCD Study®), DBSI metrics indicative of putative neuroinflammation were computed for WM tracts, hypothalamus, nucleus accumbens, caudate nucleus, and putamen. DBSI metrics were compared between children with normal-weight vs. obesity. DBSI metrics were also correlated to baseline and one- and two-year change in continuous obesity-related measures (waist circumference, BMI, and BMI z-scores). Striatal DBSI findings were compared to those of restriction spectrum imaging (RSI). Results A total of 263 nine- and ten-year old children from the ABCD Study® 2.0.1 data release (5 underweight; 126 with normal-weight; 64 with over-weight; 68 with obesity) who met inclusion and exclusion criteria were randomly selected. Relative to children with normal-weight, children with obesity had lower DBSI fiber fraction (FF; reflects apparent axonal/dendritic density) and higher DBSI restricted fraction (RF; reflects cellularity) in WM tracts throughout the brain (voxel-wise FWE-corrected p < 0.05), as well as higher DBSI-RF in the hypothalamus, nucleus accumbens, and caudate nucleus (Cohen's d's ≥ 0.28, p's ≤ 0.05). Across all children, greater baseline waist circumference was related to higher DBSI-RF in the hypothalamus (standardized β = 0.17, p = 0.0033), nucleus accumbens (standardized β = 0.21, p = 0.0001), and caudate nucleus (standardized β = 0.14, p = 0.013). Gain in waist circumference over one and two years related to higher baseline DBSI-RF in nucleus accumbens (standardized β = 0.12, p = 0.08) and in hypothalamus (standardized β = 0.15, p = 0.03), respectively. Overall, results were consistent for BMI and BMI z-scores. Similar results were observed using RSI metrics. Conclusion Novel findings include demonstration that, as in adults, childhood obesity is associated with DBSI-assessed putative neuroinflammation in WM tracts and hypothalamus. In addition, our results support the reproducibility of previous findings that MRI-assessed putative neuroinflammation in striatum and hypothalamus is related to obesity in children, contributing to a growing understanding of the role of adiposity in brain health across the lifespan.

Associations between socioeconomic status and white matter microstructure in children: indirect effects via obesity and cognition

“…As an immune response, the brain's astrocytes and microglia undergo "reactive gliosis", a process marked by their proliferation and enlargement as seen in rodent models of obesity [74][75][76][77][78] . In diffusion MRI models, such neuroinflammatory phenotype may manifest as increases in isotropic intracellular signals, a phenomenon observed in the striatum 39,42,79 and recently hypothalamus and diffuse white matter tracts 42 in childhood obesity.…”

“…We further expected that greater neighborhood disadvantage and lower household SES (i.e., income, parental education) would independently relate to white matter microstructure, paralleling the independent associations that have been seen with gray matter and function. Given known links between obesity, cognition, and white matter microstructure in children 41,42 , we hypothesized that obesity measures and cognition would have indirect effects, independent for each SES indicator , on the associations between lower SES and altered white matter microstructure, thereby boosting the plausibility of these proximal factors being causal mediators and potentially motivating their management from both community and household angles.…”

Obesidade e cognição

“…Crianças obesas apresentam maiores chances de terem sobrepeso ou de serem obesas ao atingirem a fase adulta e exibem maiores chances de desenvolverem problemas de saúde ao longo da vida, como diabetes, problemas cardíacos, câncer, doenças neurodegenerativas e mortalidade em geral. Essa condição é responsável por gerar prejuízos às funções executivas, ou seja, à diferentes dimensões cognitivas, incluindo controle inibitório, processo de tomada de decisão, memória de trabalho, e sensibilidade de recompensa, se referindo a um conjunto de processos que possibilitam o planejamento, resolução de problemas e regulação de comportamentos e emoções (Ronan et al 2020& Li et al 2023.…”

“…A obesidade envolve uma inflamação sistêmica crônica de baixo grau, afetando múltiplos órgãos (Li et al 2023). Essa condição está relacionada com o desenvolvimento de uma série de problemas de saúde, como diabetes, hipertensão, problemas cardíacos e câncer.…”

“…Além desses problemas de saúde, a obesidade também está associada com problemas na cognição, no controle motor, e com uma alteração na plasticidade cerebral (Wang et al 2015). Uma alimentação alta em gorduras pode desencadear processor inflamatórios no sistema nervoso central ou neuroinflamação, causando diversas consequências para a cognição e o comportamento (Li et al 2023).…”