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Abstract
Background and Objective 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 WAT (oWAT) and subcutaneous WAT (scWAT) with brain structure and perfusion and cognition in adults with severe obesity.
Methods Within the cross-sectional BARICO study, brain structure and 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. The number and diameter of adipocytes were quantified together with the amount of crown-like structures (CLS) as an 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 Seventy-one patients were included (mean age 45.1 ± 5.8 years; 83.1% women; mean body mass index 40.8 ± 3.8 kg/m2). scWAT showed more CLS (z = −2.72, p < 0.01, r = −0.24) and hypertrophy compared with 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 0.10–0.60), and the number of adipocytes (per mm2) was positively associated with sCoV in the nucleus accumbens (NAcc) (β = 0.34, 95% CI 0.09–0.61). Cognitive function did not correlate with any WAT parameter or 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 0.10–0.56).
Discussion 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 relationships between oWAT morphology and cerebrovascular health in obesity.
Trial Registration Information Trial Registration Number NTR7288 (trialregister.nl/trial/7090).
Glossary
- ASL=
- arterial spin labeling;
- ATT=
- arterial transit time;
- BMI=
- body mass index;
- BS=
- bariatric surgery;
- CBF=
- cerebral blood flow;
- COWAT=
- Controlled Word Association Test;
- CLS=
- crown-like structure;
- CRP=
- C-reactive protein;
- DWI=
- diffusion-weighted imaging;
- ELISAs=
- enzyme-linked immunosorbent assays;
- FPG=
- fasting plasma glucose;
- FLAIR=
- fluid-attenuated inversion recovery;
- GM=
- gray matter;
- HbA1c=
- hemoglobin A1c;
- ICV=
- intracranial volume;
- IQR=
- interquartile range;
- IL-6=
- interleukin-6;
- MoCA=
- Montreal Cognitive Assessment;
- MSMD=
- mean skeletonized mean diffusivity;
- nAcc=
- nucleus accumbens;
- ns=
- not significant;
- oWAT=
- omental WAT;
- ROI=
- region of interest;
- sCoV=
- spatial coefficient of variation;
- scWAT=
- Subcutaneous WAT;
- SAA=
- serum amyloid A;
- SIMOA=
- single-molecule array;
- TE=
- echo time;
- TI=
- inversion time;
- TR=
- repetition time;
- TAP=
- Test of Attentional Performance;
- TNF-α=
- tumor necrosis factor alpha;
- vWAT=
- visceral WAT;
- WAT=
- white adipose tissue;
- WC=
- waist circumference;
- WM=
- white matter;
- WMH=
- white matter hyperintensity
Footnotes
Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.
↵* The authors contributed equally to this work as first authors.
↵† These authors contributed equally to this work as senior authors.
Submitted and externally peer reviewed. The handling editor was Linda Hershey, MD, PhD, FAAN.
- Received April 22, 2022.
- Accepted in final form September 23, 2022.
- © 2022 American Academy of Neurology
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