肥胖症患者白色脂肪组织对大脑结构、灌注和认知功能的影响：BARICO 研究。
Impact of White Adipose Tissue on Brain Structure, Perfusion, and Cognitive Function in Patients With Severe Obesity: The BARICO Study.
机构信息
From the Department of Medical Imaging (D.V., F.S., G.L.R., M.W., A.J.K.), Anatomy, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Bariatric Surgery (D.V., W.V., W.A.H., E.J.H.), Vitalys, Part of Rijnstate Hospital, Arnhem, The Netherlands; Donders Institute for Brain (D.V., F.S., R.P.C.K., M.W., A.J.K.), Cognition, and Behavior and Radboudumc Alzheimer Center, Radboud University Medical Center, Nijmegen, The Netherlands; Department of Metabolic Health Research (F.S., R.K.), Netherlands Organisation for Applied Scientific Research (TNO), Leiden; Department of Microbiology and Systems Biology (L.V., S.Ö.), Netherlands Organisation for Applied Scientific Research (TNO), Zeist; Vincent van Gogh Institute for Psychiatry (R.P.C.K.), Venray, The Netherlands; Department of Medical Psychology and Radboudumc Alzheimer Center (R.P.C.K.), Radboud University Medical Center, Nijmegen, The Netherlands; Medical Image Analysis Center (MIAC) and Qbig (M.D.), and Department of Biomedical Engineering, University of Basel, Switzerland; Department of Radiology and Nuclear Medicine (H.J.M.M.M.), Amsterdam UMC, Amsterdam Neuroscience, The Netherlands; and Division of Human Nutrition and Health (E.J.H.), Wageningen University, The Netherlands.
出版信息
Neurology. 2023 Feb 14;100(7):e703-e718. doi: 10.1212/WNL.0000000000201538. Epub 2022 Nov 4.
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/m). scWAT showed more CLS ( = -2.72, < 0.01, = -0.24) and hypertrophy compared with oWAT (F(1,64) = 3.99, < 0.05, η = 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 mm) 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).
背景与目的
虽然肥胖与大脑健康之间的潜在病理生理学机制尚未完全阐明，但白色脂肪组织（WAT）被认为是关键因素。在肥胖中，WAT 会失调，表现为增生、肥大，最终发生炎症。这种失衡导致脂肪因子的失调分泌，影响（心血管）血管和大脑健康。在这项研究中，我们调查了网膜 WAT（oWAT）和皮下 WAT（scWAT）与严重肥胖成年人的大脑结构、灌注和认知之间的关系。
方法
在横断面 BARICO 研究中，在减肥手术（BS）前使用 MRI 和认知评估测量大脑结构和灌注以及认知功能。在 BS 期间，收集和分析 oWAT 和 scWAT 组织病理学。定量分析脂肪细胞的数量和直径以及冠状样结构（CLS）的数量，作为炎症的指标。采集血液样本以分析脂肪因子和炎症标志物。神经影像学结果包括脑容量、皮质厚度、白质（WM）完整性、WM 高信号、动脉自旋标记（ASL）的脑血流以及 ASL 空间变异系数（sCoV），反映脑血管健康。
结果
共纳入 71 例患者（平均年龄 45.1±5.8 岁；83.1%为女性；平均 BMI 为 40.8±3.8kg/m2）。与 oWAT 相比，scWAT 显示出更多的 CLS（ = -2.72， < 0.01， = -0.24）和肥大（F(1,64) = 3.99， < 0.05，η = 0.06）。脂联素水平与 scWAT（β = -0.31，95%CI -0.54 至 -0.08）和 oWAT（β = -0.33，95%CI -0.55 至 -0.09）的平均直径呈负相关。此外，oWAT 中的脂肪细胞直径与顶叶皮质的 sCoV 呈正相关（β = 0.33，95%CI 0.10-0.60），脂肪细胞数量（每毫米）与伏隔核（NAcc）的 sCoV 呈正相关（β = 0.34，95%CI 0.09-0.61）。认知功能与任何 WAT 参数或血浆标志物均无相关性。这些关联受到年龄和性别的强烈影响。NAcc 中的 sCoV 与空腹血糖呈正相关（β = 0.35，95%CI 0.10-0.56）。
讨论
scWAT 和 oWAT 在形态上不同，与血浆标志物和脑血管健康的关系也不同。尽管 scWAT 显示出更多的 CLS 和肥大，但与脑成像结果无关。然而，这项研究表明，肥胖患者的 oWAT 形态与脑血管健康之间存在重要关系。
试验注册信息
试验注册号 NTR7288（trialregister.nl/trial/7090）。
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