Obesity is associated with progressive brain structural changes.

The aim of this study was to investigate the relationship between obesity (OB) progression and brain structural changes. T1-weighted magnetic resonance images were acquired from 258 participants with overweight (OW) or OB and 74 participants with normal weight. Participants with OW or OB were divided into four groups according to BMI grades. Two-sample t tests compared disparities between the four subgroups and the participants with normal weight. We used causal structural covariance networks to examine the progressive impact of OB on brain structure. With increasing BMI values, reductions in gray matter volume originated in the left caudate nucleus, medial orbitofrontal cortex, and left insula and expanded to the right hippocampus and left lateral orbitofrontal cortex and then to the right parahippocampal gyrus, left precuneus, and left dorsolateral prefrontal cortex (p < 0.05, false discovery rate corrected). The left caudate nucleus and medial orbitofrontal cortex are the primary hubs of the directional network, exhibiting positive causality to the right hippocampus and left dorsolateral prefrontal cortex. Moreover, the right hippocampus is identified as an important transition hub. These findings suggest that changes in gray matter volume in individuals with OB may originate from reward/motivation processing regions, subsequently progressing to inhibitory control/learning memory regions, providing a new reference direction for clinical intervention and treatment of OB.