Department of Biochemistry, Biology and Genetics, Marche Polytechnic University, Ancona, Italy.
Obesity (Silver Spring). 2010 Jun;18(6):1079-84. doi: 10.1038/oby.2009.338. Epub 2009 Oct 15.
High-density lipoproteins (HDLs) play a key role in the protection against oxidative damage. The enzyme paraoxonase-1 (PON1) associated at the surface of HDL modulates the antioxidant and anti-inflammatory role of HDL. Previous studies have demonstrated a decrease of serum PON in obese patients. The aim of this study was to investigate whether modifications of PON1 activity reflect in a different ability to protect and/or repair biological membranes against oxidative damage. Thirty obese patients at different grades of obesity (BMI ranging from 30.4 to 64.0 kg/m(2)) and 62 age-matched control subjects (BMI <25 kg/m(2)) were included in the study. The ability of HDL to protect membranes against oxidative damage was studied using erythrocyte membranes oxidized with 2,2-azobis(2 amidinopropane)dihydrochloride (AAPH) (ox-membrane). The membrane lipid hydroperoxide levels were evaluated after the incubation of ox-membranes in the absence or in the presence of HDL of controls or obese patients. The results confirm that HDL exerts a protective effect against lipid peroxidation. The ability of HDL to repair erythrocyte membranes was positively correlated with HDL-PON activity and negatively correlated with lipid hydroperoxide levels in HDL. These results suggest that PON modulates the HDL repairing ability. HDL from obese patients repaired less efficiently erythrocyte membranes against oxidative damage with respect to HDL from healthy subjects. A negative relationship has been established between BMI of obese patients and the protective effect of HDL. In conclusion, the decrease of HDL-PON activity and the lower HDL protective action against membrane peroxidation in obese patients could contribute to accelerate the cellular oxidative damage and arteriosclerosis in obesity.
高密度脂蛋白(HDL)在防止氧化损伤方面起着关键作用。与 HDL 表面相关的酶对氧磷酶 1(PON1)调节 HDL 的抗氧化和抗炎作用。先前的研究表明肥胖患者血清中的 PON 减少。本研究旨在探讨 PON1 活性的改变是否反映了 HDL 保护和/或修复生物膜免受氧化损伤的不同能力。将 30 名不同肥胖程度(BMI 范围为 30.4 至 64.0 kg/m2)的肥胖患者和 62 名年龄匹配的对照组(BMI <25 kg/m2)纳入研究。使用 2,2-偶氮双(2-脒基丙烷)二盐酸盐(AAPH)(氧化膜)氧化红细胞膜来研究 HDL 保护膜免受氧化损伤的能力。在不存在或存在对照或肥胖患者的 HDL 的情况下孵育氧化膜后,评估膜脂质过氧化物水平。结果证实 HDL 对脂质过氧化具有保护作用。HDL 修复红细胞膜的能力与 HDL-PON 活性呈正相关,与 HDL 中的脂质过氧化物水平呈负相关。这些结果表明 PON 调节 HDL 的修复能力。与健康受试者的 HDL 相比,肥胖患者的 HDL 修复红细胞膜对抗氧化损伤的效率较低。肥胖患者的 BMI 与 HDL 的保护作用之间存在负相关关系。总之,肥胖患者 HDL-PON 活性降低和 HDL 对膜过氧化的保护作用降低可能导致细胞氧化损伤和肥胖症中的动脉粥样硬化加速。