Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, United States of America.
Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Seattle, WA, United States of America.
J Diabetes Complications. 2020 Dec;34(12):107693. doi: 10.1016/j.jdiacomp.2020.107693. Epub 2020 Jul 31.
High-density lipoproteins (HDL) modified by glycation have been reported to be dysfunctional. Little is known regarding the anti-inflammatory effects on adipocytes of glycated HDL.
We tested whether modification of HDL in vitro by glycolaldehyde (GAD), malondialdehyde (MDA) or glucose affected HDL's anti-inflammatory properties and ability to promote cholesterol efflux. To determine whether similar changes occur in vivo, we examined modifications of apolipoprotein A1 (APOA1) and APOA2 and anti-inflammatory and cholesterol efflux properties of HDL isolated from subjects with type 1 diabetes in poor glycemic control.
In vitro modification with both GAD and MDA blunted HDL's ability to inhibit palmitate-induced inflammation and cholesterol efflux in adipocytes. Modification of HDL by glucose had little impact on HDL function, like the response using HDL isolated from subjects with diabetes. Mass spectrophotometric analysis revealed that lysine residues in APOA1 and APOA2 of HDL modified by GAD and MDA in vitro differed from those modified by glucose, which resembled that seen with HDL from patients with type1 diabetes.
Modification of lysine residues in HDL by GAD and MDA in vitro does not mirror the HDL glycation in vivo in patients with diabetes, but resembles HDL modified in vitro by glucose.
已报道经糖基化修饰的高密度脂蛋白（HDL）功能失调。关于糖基化 HDL 对脂肪细胞的抗炎作用知之甚少。
我们检测了体外由乙二醛（GAD）、丙二醛（MDA）或葡萄糖修饰 HDL 是否会影响 HDL 的抗炎特性和促进胆固醇流出的能力。为了确定体内是否发生类似的变化，我们研究了 1 型糖尿病患者血糖控制不佳时 HDL 中载脂蛋白 A1（APOA1）和 APOA2 的修饰以及 HDL 的抗炎和胆固醇流出特性。
体外用 GAD 和 MDA 修饰均可削弱 HDL 抑制棕榈酸诱导的脂肪细胞炎症和胆固醇流出的能力。葡萄糖修饰 HDL 对 HDL 功能的影响很小，与糖尿病患者 HDL 的反应相似。质谱分析显示，体外用 GAD 和 MDA 修饰的 HDL 中 APOA1 和 APOA2 的赖氨酸残基与葡萄糖修饰的 HDL 不同，与 1 型糖尿病患者的 HDL 相似。
体外用 GAD 和 MDA 修饰 HDL 中的赖氨酸残基与糖尿病患者体内的 HDL 糖基化并不相似，但与体外用葡萄糖修饰的 HDL 相似。
