The growing global obesity issue emphasizes the importance of understanding its health implications. Previous research has identified consistent alterations in gray matter (GM) volume in connection with obesity. Given the various implications of distinct fat compartments and the potential role of adipose tissue-derived adipokines in brain health, a more detailed investigation of adiposity is required. This study investigates a sample of 65 males with varying body mass indices to explore the relationship between various fat compartments, adipokine levels, and volumetric GM variations, aiming to provide a deeper understanding of the interplay between adiposity, brain structure, and metabolic signals. Whole-body magnetic resonance imaging (MRI) was used to assess total, visceral, and subcutaneous adipose tissue, while MR spectroscopy was performed to capture liver fat content. For the assessment of adipokine levels leptin and adiponectin concentrations were measured, and structural brain images underwent cortical and subcortical segmentation for GM volume and thickness. A predictive modeling approach with leave-one-out cross-validation was used to predict body composition metrics and adipokine levels based on structural GM data. Our investigation revealed diminished GM volume and thickness correlated with elevated leptin levels in areas crucial for appetite regulation, decision-making, and cognitive control, including the anterior insula, orbitofrontal cortex, and anterior cingulate cortex. These findings suggest a potential adverse impact of heightened leptin concentrations on brain health and eating habits. Contrary to expectations, our investigation found no significant relationship between GM volume and any of the measured fat compartments. This result prompts the need for further research to elucidate the relationship between obesity, adipokines, and brain structure.|This study reveals a negative impact of elevated leptin levels on gray matter volume and thickness in brain regions regulating eating behavior and cognitive control. This finding potentially offers promising implications for addressing adverse outcomes associated with obesity. image