Detopoulou Paraskevi, Nomikos Tzortzis, Fragopoulou Elizabeth, Antonopoulou Smaragdi
Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, 70, El. Venizelou St. Kallithea, 17671 Athens, Greece.
Curr Vasc Pharmacol. 2021;19(6):663-672. doi: 10.2174/1570161119666210628125239.
Platelet-activating-factor (PAF) is a lipid inflammatory mediator implicated in liver disease. Its main biosynthetic enzymes are cytidine diphosphate (CDP)-choline: 1-alkyl-2-acetyl-sn-glycerol-cholinephosphotransferase (PAF-CPT) and acetyl-coenzyme A: lyso-PAF-acetyltransferases (Lyso-PAF-AT). At the same time, PAF acetylhydrolase (PAF-AH) and lipoprotein-associated phospholipase A2 (Lp-PLA ) degrade PAF.
To explore the relation of PAF metabolism with liver diseases and non-alcoholic fatty liver disease, as reflected by the fatty liver index (FLI).
In 106 healthy volunteers, PAF concentration, the activity of its metabolic enzymes and gamma-glutamyl transferase (GGT) were measured in whole blood, leukocytes and serum, respectively and the FLI was calculated. Partial correlations and linear regression models were used.
In males, serum GGT activity was positively correlated with abdominal fat (as assessed by analysis of a manually defined region of interest in dual-energy X-ray absorptiometry), triacylglycerols, bound-PAF and Lp-PLA , while the FLI was positively correlated with Lp-PLA activity. In females, serum GGT activity was negatively associated with high-density lipoprotein cholesterol (HDL-C) (age adjusted correlations, all p<0.05). Lp-PLA was a significant determinant of serum GGT activity in males after controlling for age, low- density lipoprotein cholesterol (LDL-C) and abdominal fat. The addition of bound-PAF in the model significantly increased the explained variance of serum GGT activity (total variance explanation 30%).
Bound-PAF and Lp-PLA activity predicted serum GGT activity while Lp-PLA was also related to FLI. Our findings shed light on the metabolic pathways linking Lp-PLA to other atherosclerosis and/or oxidative markers, such as HDL-C, LDL-C, GGT and FLI and underline the important role of PAF.
血小板活化因子（PAF）是一种与肝脏疾病有关的脂质炎症介质。其主要生物合成酶是胞苷二磷酸（CDP）-胆碱：1-烷基-2-乙酰基-sn-甘油-胆碱磷酸转移酶（PAF-CPT）和乙酰辅酶A：溶血PAF-乙酰转移酶（Lyso-PAF-AT）。同时，PAF乙酰水解酶（PAF-AH）和脂蛋白相关磷脂酶A2（Lp-PLA₂）可降解PAF。
探讨以脂肪肝指数（FLI）反映的PAF代谢与肝脏疾病及非酒精性脂肪性肝病的关系。
对106名健康志愿者分别测定全血、白细胞和血清中的PAF浓度、其代谢酶活性及γ-谷氨酰转移酶（GGT），并计算FLI。采用偏相关性和线性回归模型。
在男性中，血清GGT活性与腹部脂肪（通过双能X线吸收法手动定义的感兴趣区域分析评估）、三酰甘油、结合型PAF和Lp-PLA₂呈正相关，而FLI与Lp-PLA₂活性呈正相关。在女性中，血清GGT活性与高密度脂蛋白胆固醇（HDL-C）呈负相关（年龄校正相关性，均p<0.05）。在控制年龄、低密度脂蛋白胆固醇（LDL-C）和腹部脂肪后，Lp-PLA₂是男性血清GGT活性的重要决定因素。模型中加入结合型PAF可显著增加血清GGT活性的解释方差（总方差解释率30%）。
结合型PAF和Lp-PLA₂活性可预测血清GGT活性，而Lp-PLA₂也与FLI有关。我们的研究结果揭示了将Lp-PLA₂与其他动脉粥样硬化和/或氧化标志物（如HDL-C、LDL-C、GGT和FLI）联系起来的代谢途径，并强调了PAF的重要作用。
