高密度脂蛋白中高水平的氧化脂肪酸会损害糖尿病患者高密度脂蛋白的抗氧化功能。
High levels of oxidized fatty acids in HDL impair the antioxidant function of HDL in patients with diabetes.
机构信息
College of Health Science and Environmental Engineering, Shenzhen Technology University, Shenzhen Guangdong, China.
Department of Endocrinology, Shenzhen Sami Medical Center (The Fourth People's Hospital of Shenzhen), Shenzhen Guangdong, China.
出版信息
Front Endocrinol (Lausanne). 2022 Oct 20;13:993193. doi: 10.3389/fendo.2022.993193. eCollection 2022.
AIMS
Previous studies demonstrate that the antioxidant functions of high-density lipoprotein (HDL) are impaired in diabetic patients. The composition of HDL plays an important role in maintaining the normal functionality of HDL. In this study, we compared the levels of oxidized fatty acids in HDL from diabetic subjects and non-diabetic healthy controls, aiming to investigate the role of oxidized fatty acids in the antioxidant property of HDL.
METHODS
HDL was isolated from healthy subjects (n=6) and patients with diabetes (n=6, hemoglobin A1c ≥ 9%, fasting glucose ≥ 7 mmol/L) using a dextran sulfate precipitation method. Cholesterol efflux capacity mediated by HDL was measured on THP-1 derived macrophages. The antioxidant capacity of HDL was evaluated with dichlorofluorescein-based cellular assay in human aortic endothelial cells. Oxidized fatty acids in HDL were determined by liquid chromatography-tandem mass spectrometry. The correlations between the levels of oxidized fatty acids in HDL and the endothelial oxidant index in cells treated with HDLs were analyzed through Pearson's correlation analyses, and the effects of oxidized fatty acids on the antioxidant function of HDL were verified .
RESULTS
The cholesterol efflux capacity of HDL and the circulating HDL-cholesterol were similar in diabetic patients and healthy controls, whereas the antioxidant capacity of HDL was significantly decreased in diabetic patients. There were higher levels of oxidized fatty acids in HDL isolated from diabetic patients, which were strongly positively correlated with the oxidant index of cells treated with HDLs. The addition of a mixture of oxidized fatty acids significantly disturbed the antioxidant activity of HDL from healthy controls, while the apolipoprotein A-I mimetic peptide D-4F could restore the antioxidant function of HDL from diabetic patients.
CONCLUSION
HDL from diabetic patients displayed substantially impaired antioxidant activity compared to HDL from healthy subjects, which is highly correlated with the increased oxidized fatty acids levels in HDL.
目的
先前的研究表明，糖尿病患者的高密度脂蛋白（HDL）的抗氧化功能受损。HDL 的组成在维持 HDL 的正常功能方面起着重要作用。在这项研究中，我们比较了糖尿病患者和非糖尿病健康对照者 HDL 中氧化脂肪酸的水平，旨在研究氧化脂肪酸在 HDL 抗氧化特性中的作用。
方法
采用葡聚糖硫酸沉淀法从健康受试者（n=6）和糖尿病患者（n=6，糖化血红蛋白≥9%，空腹血糖≥7mmol/L）中分离 HDL。用 THP-1 衍生的巨噬细胞测量 HDL 介导的胆固醇流出能力。用二氯荧光素基于细胞的测定法在人主动脉内皮细胞中评估 HDL 的抗氧化能力。通过液相色谱-串联质谱法测定 HDL 中的氧化脂肪酸。通过 Pearson 相关分析分析 HDL 中氧化脂肪酸的水平与用 HDL 处理的细胞中内皮氧化剂指数之间的相关性，并验证氧化脂肪酸对 HDL 抗氧化功能的影响。
结果
糖尿病患者和健康对照者的 HDL 胆固醇流出能力和循环 HDL-胆固醇相似，而 HDL 的抗氧化能力在糖尿病患者中显著降低。从糖尿病患者中分离出的 HDL 中氧化脂肪酸水平更高，与用 HDL 处理的细胞的氧化剂指数呈强烈正相关。添加氧化脂肪酸混合物显著扰乱了来自健康对照者的 HDL 的抗氧化活性，而载脂蛋白 A-I 模拟肽 D-4F 可以恢复糖尿病患者的 HDL 的抗氧化功能。
结论
与健康对照者的 HDL 相比，糖尿病患者的 HDL 表现出明显受损的抗氧化活性，这与 HDL 中氧化脂肪酸水平的升高高度相关。
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