糖基磷脂酰肌醇锚定高密度脂蛋白结合蛋白 1 和血管生成素样蛋白 4 与糖尿病患者心外膜脂肪组织中脂蛋白脂肪酶活性的增加相关。
Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 and angiopoietin-like protein 4 are associated with the increase of lipoprotein lipase activity in epicardial adipose tissue from diabetic patients.
机构信息
Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Fisiopatología y Bioquímica Clínica (INFIBIOC), Departamento de Bioquímica Clínica, Laboratorio de Lípidos y Aterosclerosis, Buenos Aires, Argentina.
Universidad de Buenos Aires, CONICET, Instituto de Investigaciones Biomédicas en Retrovirus y SIDA (INBIRS), Facultad de Medicina, Buenos Aires, Argentina.
出版信息
Atherosclerosis. 2019 Sep;288:51-59. doi: 10.1016/j.atherosclerosis.2019.06.915. Epub 2019 Jul 6.
BACKGROUND AND AIMS
Epicardial adipose tissue (EAT) is a visceral AT, surrounding myocardium and coronary arteries. Its volume is higher in Type 2 diabetic (DM2) patients, associated with cardiovascular disease risk. Lipoprotein lipase (LPL) hydrolyses triglycerides (TG) from circulating lipoproteins, supplying fatty acids to AT, contributing to its expansion. We aimed to evaluate LPL expression and activity in EAT from DM2 and no DM2 patients, and its regulators ANGPTL4, GPIHBP1 and PPARγ levels, together with VLDLR expression and EAT LPL association with VLDL characteristics.
METHODS
We studied patients undergoing coronary by-pass graft (CABG) divided into CABG-DM2 (n = 21) and CABG-noDM2 (n = 29), and patients without CABG (No CABG, n = 30). During surgery, EAT and subcutaneous AT (SAT) were obtained, in which LPL activity, gene and protein expression, its regulators and VLDLR protein levels were determined. Isolated circulating VLDLs were characterized.
RESULTS
EAT LPL activity was higher in CABG-DM2 compared to CABG-noDM2 and No CABG (p=0.002 and p<0.001) and in CABG-noDM2 compared to No CABG (p=0.02), without differences in its expression. ANGPTL4 levels were higher in EAT from No CABG compared to CABG-DM2 and CABG-noDM2 (p<0.001). GPIHBP1 levels were higher in EAT from CABG-DM2 and CABG-noDM2 compared to No CABG (p= 0.04). EAT from CABG-DM2 presented higher PPARγ levels than CABG-noDM2 and No CABG (p=0.02 and p=0.03). No differences were observed in VLDL composition between groups, although EAT LPL activity was inversely associated with VLDL-TG and TG/protein index (p<0.05).
CONCLUSIONS
EAT LPL regulation would be mainly post-translational. The higher LPL activity in DM2 could be partly responsible for the increase in EAT volume.
背景与目的
心外膜脂肪组织（EAT）是一种内脏脂肪组织，围绕着心肌和冠状动脉。2 型糖尿病（DM2）患者的 EAT 体积更高，与心血管疾病风险相关。脂蛋白脂肪酶（LPL）可从循环脂蛋白中水解甘油三酯（TG），为脂肪组织提供脂肪酸，促进其扩张。我们旨在评估 DM2 和非 DM2 患者的 EAT 中的 LPL 表达和活性，以及其调节剂血管生成素样蛋白 4（ANGPTL4）、GPIHBP1 和过氧化物酶体增殖物激活受体γ（PPARγ）水平，以及 VLDLR 表达和 EAT LPL 与 VLDL 特征的关系。
方法
我们研究了接受冠状动脉旁路移植术（CABG）的患者，分为 CABG-DM2（n=21）和 CABG-非 DM2（n=29）和未接受 CABG 的患者（无 CABG，n=30）。在手术过程中，从 EAT 和皮下脂肪组织（SAT）中获取 EAT 和 SAT，测定 LPL 活性、基因和蛋白表达、其调节剂和 VLDLR 蛋白水平。还对分离的循环 VLDL 进行了特征分析。
结果
与 CABG-非 DM2 和无 CABG 相比，CABG-DM2 患者的 EAT LPL 活性更高（p=0.002 和 p<0.001），与无 CABG 相比，CABG-非 DM2 患者的 EAT LPL 活性也更高（p=0.02），但 LPL 表达没有差异。无 CABG 患者的 EAT 中 ANGPTL4 水平高于 CABG-DM2 和 CABG-非 DM2 患者（p<0.001）。CABG-DM2 和 CABG-非 DM2 患者的 EAT 中 GPIHBP1 水平高于无 CABG 患者（p=0.04）。与 CABG-非 DM2 和无 CABG 相比，CABG-DM2 患者的 EAT 中 PPARγ 水平更高（p=0.02 和 p=0.03）。各组间 VLDL 组成无差异，但 EAT LPL 活性与 VLDL-TG 和 TG/蛋白指数呈负相关（p<0.05）。
结论
EAT LPL 的调节主要是翻译后。DM2 中较高的 LPL 活性可能是 EAT 体积增加的部分原因。
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