Mapping obesity-related traits with regional white matter microstructure highlights the importance of brainstem tracts and sex-related differences

Background and aims The relationships between obesity-related traits and the brain’s white matter characteristics and the context of sex- and age-related differences, remain unclear. This study aims to elucidate these body-brain connections using a large-scale dataset. Methods We analyzed data from 40,040 participants from the UK Biobank (52.2% female; ages 44-83 years) using multiple linear regression to evaluate associations between obesity-related traits (obesity, body anthropometrics) and white matter diffusion tensor imaging (DTI) metrics (fractional anisotropy, axial diffusivity, radial diffusivity, mean diffusivity). We also examined interactions with age and sex. Results Our analyses revealed significant associations between obesity-related traits and DTI metrics with partial correlation coefficient |r| effect sizes ranging from 0.02 to 0.20 for most regions of interest with largest effects in brainstem tracts. We observed more widespread sex-by-obesity-related than age-by-obesity-related interaction effects on DTI metrics. Conclusions Our results link obesity-related traits and white matter phenotypes, suggesting that shared body fat-related pathways linking physical and brain health that may vary based on sex and age. Understanding these relationships could enhance the development and evaluation of targeted, individualized, treatment strategies for conditions that co-occur with obesity, although further longitudinal studies are needed to map the dynamics of these associations.