Bajnok Laszlo, Seres Ildiko, Varga Zsuzsa, Jeges Sara, Peti Attila, Karanyi Zsolt, Juhasz Attila, Csongradi Eva, Mezosi Emese, Nagy Endre V, Paragh Gyorgy
1st Department of Medicine, School of Medicine, University of Pécs, Pécs, Hungary H-7624 Pécs, Hungary.
Metabolism. 2007 Nov;56(11):1542-9. doi: 10.1016/j.metabol.2007.06.022.
Altered activities of high-density lipoprotein (HDL)-associated antioxidant enzyme paraoxonase 1 (PON1) and lipid transfer proteins, for example, cholesteryl ester transfer protein (CETP) and lecithin cholesterol acyltransferase (LCAT), participating in lipoprotein remodeling seem to play important roles in obesity-related accelerated atherosclerosis. Inverse associations of PON1 with obesity and serum leptin levels have been demonstrated. However, the relationship of leptin with CETP and LCAT in humans is less clear. Our aims were to investigate whether the elevated leptin level is (a) an independent predictor of low PON1 and (b) associated with alterations of CETP and LCAT activities. Seventy-four white subjects forming 3 age- and sex-matched groups were included into the study (groups 1 and 2: nondiabetic obese patients, n = 25 with body mass index [BMI] 28-39.9 kg/m2 and n = 25 with BMI >or=40 kg/m2, respectively; and group 3: 24 healthy, normal-weight control subjects). Paraoxonase 1 correlated inversely with BMI (r = -0.39, P < .01), waist circumferences (r = -0.42, P < .001), and leptin concentrations (r = -0.38, P < .001). However, in a multiple regression model, neither these variables nor others, for example, age, sex, blood pressure, insulin resistance (in homeostasis model assessment of insulin resistance [HOMA-IR]), HDL cholesterol, low-density lipoprotein cholesterol, or lipid peroxidation (measured as thiobarbituric acid reactive substances), proved to be independent predictors of PON1. Lecithin cholesterol acyltransferase correlated negatively with BMI (r = -0.40, P < .01), waist circumferences (r = -0.42, P < .001), and leptin levels (r = -0.40, P < .01). During multiple regression analyses, BMI was an independent predictor of LCAT after adjustments for age, sex, HOMA-IR, and HDL cholesterol. However, this was replaced by leptin and HOMA-IR when leptin was also included into the model. The CETP activities correlated with HOMA-IR (r = 0.33, P < .01), thiobarbituric acid reactive substances (r = 0.45, P < .001), and leptin (r = 0.36, P < .01) levels in univariate but not in multivariate models. Elevated leptin level is an independent predictor of low LCAT, but not PON1, activity. In a population with a wide range of BMI, LCAT correlates inversely with obesity and CETP directly with insulin resistance.
高密度脂蛋白（HDL）相关抗氧化酶对氧磷酶1（PON1）以及参与脂蛋白重塑的脂质转运蛋白，如胆固醇酯转运蛋白（CETP）和卵磷脂胆固醇酰基转移酶（LCAT）的活性改变，似乎在肥胖相关的动脉粥样硬化加速过程中发挥重要作用。PON1与肥胖和血清瘦素水平呈负相关。然而，瘦素与人类CETP和LCAT的关系尚不清楚。我们的目的是研究瘦素水平升高是否（a）是低PON1的独立预测因素，以及（b）与CETP和LCAT活性的改变有关。74名白人受试者组成3个年龄和性别匹配的组纳入研究（第1组和第2组：非糖尿病肥胖患者，分别为25名体重指数[BMI]为28 - 39.9 kg/m²和25名BMI≥40 kg/m²；第3组：24名健康、体重正常的对照受试者）。对氧磷酶1与BMI呈负相关（r = -0.39，P <.01）、腰围呈负相关（r = -0.42，P <.001）以及瘦素浓度呈负相关（r = -0.38，P <.001）。然而，在多元回归模型中，这些变量以及其他变量，如年龄、性别、血压、胰岛素抵抗（采用胰岛素抵抗稳态模型评估[HOMA-IR]）、HDL胆固醇、低密度脂蛋白胆固醇或脂质过氧化（以硫代巴比妥酸反应性物质衡量），均未被证明是PON1的独立预测因素。卵磷脂胆固醇酰基转移酶与BMI呈负相关（r = -0.40，P <.01）、腰围呈负相关（r = -0.42，P <.001）以及瘦素水平呈负相关（r = -0.40，P <.01）。在多元回归分析中，调整年龄、性别、HOMA-IR和HDL胆固醇后，BMI是LCAT的独立预测因素。然而，当模型中也纳入瘦素时，这一因素被瘦素和HOMA-IR所取代。在单变量模型中，CETP活性与HOMA-IR（r = 0.33，P <.01）、硫代巴比妥酸反应性物质（r = 0.45，P <.001）和瘦素（r = 0.36，P <.01）水平相关，但在多变量模型中并非如此。瘦素水平升高是低LCAT活性而非PON1活性的独立预测因素。在BMI范围广泛的人群中，LCAT与肥胖呈负相关，CETP与胰岛素抵抗呈正相关。
