The escalating global obesity epidemic underscores the need to understand its intricate health implications. Research highlights associations between elevated body mass index (BMI) and structural changes in both white and gray matter (WM, GM). Given the indirect nature of BMI as an indicator of adiposity, a comprehensive evaluation of body composition becomes essential. This study explores distinct adipose tissue compartments, adipokine levels, and their interplay with structural alterations in both WM and GM, elucidating the complex relationship between obesity, brain structure, and metabolic signals.Using whole-body magnetic resonance imaging (MRI), we assessed total, visceral, subcutaneous adipose tissue (TAT, VAT, SAT) and liver fat content in 65 males. Structural MRI evaluated GM volume, while diffusion-weighted imaging assessed WM connectivity. Leptin and adiponectin concentrations were measured. Predictive modeling was used to link brain volume and connectivity data to body composition metrics and metabolic signals.Our investigation revealed increased WM connectivity associated with elevated BMI, TAT, and SAT in the insula, frontal pole, middle frontal gyrus, orbitofrontal cortex, and anterior cingulate cortex. Conversely, reduced GM volume in the insula, orbitofrontal cortex, and anterior cingulate cortex correlated with elevated leptin levels. No significant relationships emerged between GM volume and fat compartments. These findings illuminate altered neural communication in brain regions crucial for appetite regulation, reward processing, decision-making, and inhibitory control in individuals with obesity, potentially contributing to weight gain. While providing valuable insights, further research is essential to understand underlying neural changes and to develop effective obesity prevention and treatment strategies.