Grao-Cruces Elena, Millan-Linares Maria C, Martin-Rubio Maria E, Toscano Rocio, Barrientos-Trigo Sergio, Bermudez Beatriz, Montserrat-de la Paz Sergio
Department of Medical Biochemistry, Molecular Biology, and Immunology, School of Medicine, University of Seville, 41009 Seville, Spain.
Department of Food & Health, Institute of Fat, Spanish National Research Council, 41013 Seville, Spain.
Biomedicines. 2021 Nov 19;9(11):1722. doi: 10.3390/biomedicines9111722.
High-density lipoproteins (HDLs) play an important role in reverse cholesterol transport and present antioxidant properties, among others. In the central nervous system (CNS), there are HDLs, where these lipoproteins could influence brain health. Owing to the new evidence of HDL functionality remodeling in obese patients, and the fact that obesity-associated metabolic disturbances is pro-inflammatory and pro-oxidant, the aim of this study was to investigate if HDL functions are depleted in obese patients and obesity-associated microenvironment. HDLs were isolated from normal-weight healthy (nwHDL) and obese men (obHDL). The oxHDL level was measured by malondialdehyde and 4-hydroxynoneal peroxided products. BV2 microglial cells were exposed to different concentrations of nwHDL and obHDL in different obesity-associated pro-inflammatory microenvironments. Our results showed that hyperleptinemia increased oxHDL levels. In addition, nwHDLs reduced pro-inflammatory cytokines' release and M1 marker gene expression in BV2 microglial cells. Nevertheless, both nwHDL co-administered with LPS+leptin and obHDL promoted BV2 microglial activation and a higher pro-inflammatory cytokine production, thus confirming that obesity-associated metabolic disturbances reverse the antioxidant and anti-inflammatory properties of HDLs in microglial cells.
高密度脂蛋白（HDL）在逆向胆固醇转运中发挥着重要作用，除此之外还具有抗氧化特性。在中枢神经系统（CNS）中存在HDL，这些脂蛋白可能会影响大脑健康。鉴于肥胖患者中HDL功能重塑的新证据，以及肥胖相关代谢紊乱具有促炎和促氧化的特性，本研究的目的是调查肥胖患者及肥胖相关微环境中HDL功能是否受损。从体重正常的健康男性（nwHDL）和肥胖男性（obHDL）中分离出HDL。通过丙二醛和4-羟基壬烯醛过氧化产物来测量氧化型HDL（oxHDL）水平。将BV2小胶质细胞暴露于不同肥胖相关促炎微环境中的不同浓度的nwHDL和obHDL中。我们的结果表明，高瘦素血症会增加oxHDL水平。此外，nwHDL可减少BV2小胶质细胞中促炎细胞因子的释放和M1标志物基因的表达。然而，与脂多糖+瘦素共同给药的nwHDL和obHDL均会促进BV2小胶质细胞的活化和更高的促炎细胞因子产生，从而证实肥胖相关代谢紊乱会逆转小胶质细胞中HDL的抗氧化和抗炎特性。
