Impact of White Adipose Tissue on Brain Structure, Perfusion, and Cognitive Function in Patients With Severe Obesity

Abstract

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.

Long-Term Brain Structure and Cognition Following Bariatric Surgery

“…Output WMH segmentation masks were used to determine WMH volume. Global WM mean diffusivity was assessed using diffusion MRI data processed as previously outlined . We calculated mean skeletonized mean diffusivity (MSMD) via an accessible method…”

Understanding the combined effects of sleep deprivation and acute social stress on cognitive performance using a comprehensive approach

“…The obtained EDTA plasma was stored at −70 °C until use. The frozen plasma samples were transferred to TNO Metabolic Health Research (Leiden, Netherlands) for biomarker analysis following protocols described in previous literature ( Schutte et al, 2022 ; Vreeken et al, 2022 ). This included an assessment of systemic inflammation using cytokine multiplex panels (Human 10plex Cytokine Panel 1, Quanterix, Billerica, USA).…”

Neuro-Adipokine Crosstalk in Alzheimer’s Disease

“…Both generalized and VAT are associated with reduced cognitive function, after adjustment for cardiovascular risk factors and vascular brain injury [ 13 ]. Interestingly, subcutaneous WAT and omental WAT are associated with different plasma markers and cerebrovascular health in severely obese patients [ 47 ]. While subcutaneous WAT demonstrates more crown-like structures, indicative of inflammation and hypertrophy, there is no association between subcutaneous WAT parameters and brain health.…”

“…While subcutaneous WAT demonstrates more crown-like structures, indicative of inflammation and hypertrophy, there is no association between subcutaneous WAT parameters and brain health. On the other hand, omental WAT is positively related to greater variability in CBF, indicating vascular and perfusion abnormalities, in the parietal lobe and nucleus accumbens [ 47 ]. Furthermore, aging is associated with the accumulation of ectopic fat, which is correlated with an increased risk of cardiometabolic disorders [ 48 , 49 ].…”