Volumetric brain alterations associated with a high-fat, high-fructose obesogenic diet: Insights from cross-sectional and longitudinal MRI in mice.

Childhood obesity is associated with altered brain structure in humans, but the causal role of obesogenic diets and the longitudinal trajectory of these changes remain poorly understood. This study investigates the impact of a high-fat, high-fructose (HFHF) diet on brain volumetrics in mice using cross-sectional and longitudinal MRI. Mice were fed either a control chow or HFHF diet starting at 6 weeks of age. Structural MRI and voxel-based morphometry (VBM) were performed at 14 weeks (after 8 weeks of diet) and 6 months to quantify total brain and regional volumes (neocortex, hippocampus, subregions). Body weights were monitored throughout. HFHF-fed mice exhibited significant weight gain. Cross-sectionally, obese mice showed reduced total brain volume and increased neocortical volumes (mid- and posterior regions, alongside persistent posterior hippocampal decreases). Longitudinally, obese mice displayed an increase of total brain volume by 6 months, contrasting with age-associated decrease in controls. VBM revealed obesity-specific reductions in basal forebrain, sensory cortices, and hippocampal subfields, distinct from normative aging. Early-life obesogenic diets induce dynamic, region-specific brain alterations in mice, including increased neocortical and decreased hippocampal volumes. Longitudinal MRI captures dynamic volumetric trajectories providing insights into how obesogenic diets disrupt neurodevelopment.