Department of Internal Medicine III, Giessen University Hospital, Gießen, Germany.
Department of Neurology, Giessen University Hospital, Gießen, Germany.
J Clin Endocrinol Metab. 2021 Apr 23;106(5):e2239-e2250. doi: 10.1210/clinem/dgaa983.
Data on the presence/quantification of the neurotrophic adipokines retinol-binding protein-4 (RBP4), clusterin, and pigment epithelium-derived factor (PEDF) in human cerebrospinal fluid (CSF) are scarce and migration of these adipokines across of the blood-brain barrier (BBB) is uncertain.
This work aimed to quantify RBP4, PEDF, and clusterin in paired serum and CSF samples of patients undergoing neurological evaluation.
A total of 268 patients (109 male, 159 female) were included. Adipokine serum and CSF concentrations were measured by enzyme-linked immunosorbent assay in duplicate.
RBP4 was abundant in serum (mean, 31.9 ± 24.2 μg/mL). The serum concentrations were approximately 145 times higher than in CSF (CSF to serum RBP4 ratio, 8.2 ± 4.3 × 10-3). PEDF was detectable in serum (mean, 30.2 ± 11.7 μg/mL) and concentrations were approximately 25 times higher than in CSF (CSF to serum PEDF ratio, 42.3 ± 15.6 × 10-3). Clusterin serum concentrations were abundant with mean levels of 346.0 ± 114.6 μg/mL, which were approximately 40 times higher than CSF levels (CSF to serum clusterin ratio, 29.6 ± 23.4 × 10-3). RBP4 and PEDF serum levels correlated positively with CSF levels, which were increased in overweight/obese patients and in type 2 diabetic patients. The CSF concentrations of all 3 adipokines increased with BBB dysfunction. RBP4 in CSF correlated positively with inflammatory parameters. In detail, only RBP4 showed the kinetics and associations that are mandatory for a putative mediator of the fat-brain axis.
RBP4, PEDF, and clusterin are permeable to the BBB and increase with the measure of BBB dysfunction. RBP4 represents an inflammatory neurotrophic adipokine and is a promising mediator of the fat-brain axis.
关于神经营养脂肪因子视黄醇结合蛋白 4（RBP4）、簇蛋白和色素上皮衍生因子（PEDF）在人脑脊液（CSF）中的存在/定量的数据很少，这些脂肪因子穿过血脑屏障（BBB）的迁移也不确定。
本研究旨在定量检测接受神经评估的患者配对血清和 CSF 样本中的 RBP4、PEDF 和簇蛋白。
共纳入 268 例患者（男 109 例，女 159 例）。采用酶联免疫吸附试验（ELISA）双份检测脂肪因子血清和 CSF 浓度。
RBP4 在血清中含量丰富（平均值为 31.9±24.2μg/mL）。血清浓度大约是 CSF 中的 145 倍（CSF 与血清 RBP4 比值为 8.2±4.3×10-3）。PEDF 可在血清中检测到（平均值为 30.2±11.7μg/mL），浓度大约是 CSF 中的 25 倍（CSF 与血清 PEDF 比值为 42.3±15.6×10-3）。簇蛋白血清浓度丰富，平均水平为 346.0±114.6μg/mL，大约是 CSF 水平的 40 倍（CSF 与血清簇蛋白比值为 29.6±23.4×10-3）。RBP4 和 PEDF 血清水平与 CSF 水平呈正相关，在超重/肥胖患者和 2 型糖尿病患者中升高。所有 3 种脂肪因子的 CSF 浓度均随 BBB 功能障碍而增加。CSF 中 RBP4 与炎症参数呈正相关。具体来说，只有 RBP4 显示出了作为脂肪-脑轴潜在介质所必需的动力学和相关性。
RBP4、PEDF 和簇蛋白可透过 BBB，并随 BBB 功能障碍的测量值而增加。RBP4 是一种具有炎症性神经营养作用的脂肪因子，是脂肪-脑轴的一个有前途的介质。
