Introduction:While underlying pathophysiology linking obesity to brain health is not completely understood, white adipose tissue (WAT) is considered a key player. In obesity, WAT becomes dysregulated, showing hyperplasia, hypertrophy and eventually inflammation. This disbalance leads to dysregulated secretion of adipokines influencing both (cardio)vascular and brain health. Within this study we investigated the association between omental (oWAT) and subcutaneous WAT (scWAT) with brain structure, perfusion and cognition in adults with severe obesity.Methods:Within the cross-sectional BARICO study, brain structure, perfusion and cognitive function were measured before bariatric surgery (BS) using MRI and cognitive assessments. During BS, oWAT and scWAT depots were collected and analyzed by histopathology. Number and diameter of adipocytes were quantified together with amount of crown-like structures (CLS) as indication of inflammation. Blood samples were collected to analyze adipokines and inflammatory markers. Neuroimaging outcomes included brain volumes, cortical thickness, white matter (WM) integrity, WM hyperintensities, cerebral blood flow using arterial spin labeling (ASL) and the ASL spatial coefficient of variation (sCoV), reflecting cerebrovascular health.Results:71 patients were included (mean age 45.1±5.8 years; 83.1% women; mean BMI 40.8±3.8). scWAT showed more CLS (Z=-2.72, p<0.01, r=-0.24) and hypertrophy compared to oWAT (F(1,64)=3.99, p<0.05, η2=0.06). Adiponectin levels were inversely associated with the average diameter of scWAT (β=-0.31, 95%CI -0.54 to -0.08) and oWAT (β=-0.33, 95%CI -0.55 to -0.09). Furthermore, the adipocyte diameter in oWAT was positively associated with the sCoV in the parietal cortex (β=0.33, 95%CI 0.10 to 0.60) and the number of adipocytes (per mm2) was positively associated with sCoV in the nucleus accumbens (NAcc) (β=0.34, 95%CI 0.09 to 0.61). Cognitive function did not correlate with any WAT parameter nor plasma marker. These associations were highly influenced by age and sex. sCoV in the NAcc was positively associated with fasting plasma glucose (β=0.35, 95%CI 0.10 to 0.56).Conclusion:scWAT and oWAT are different in morphology and in their relationship with plasma markers and cerebrovascular health. Although scWAT showed more CLS and hypertrophy, scWAT was not associated with brain readouts. This study showed however important relations between oWAT morphology and cerebrovascular health in obesity.