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肥胖儿童和青少年的血管炎症和胆固醇逆向转运及脂质代谢受损。

Vascular inflammation and impaired reverse cholesterol transport and lipid metabolism in obese children and adolescents.

机构信息

Laboratorio de Lípidos y Aterosclerosis, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.

Servicio de Nutrición y Diabetes, Hospital de Niños "Ricardo Gutiérrez", Buenos Aires, Argentina.

出版信息

Nutr Metab Cardiovasc Dis. 2022 Jan;32(1):258-268. doi: 10.1016/j.numecd.2021.09.025. Epub 2021 Oct 7.

Abstract

BACKGROUND AND AIMS

Childhood obesity is associated to complications such as insulin resistance and dyslipidemia. High density lipoproteins (HDL) constitute the only lipoprotein fraction with ateroprotective properties. The aim of the present study was to analyze inflammatory markers, carbohydrate metabolism, lipid profile and HDL functionality in obese children and adolescents compared to healthy controls.

METHODS AND RESULTS

Twenty obese children and adolescents (Body mass index z score >3.0) (9-15 years old) and 20 age and sex similar controls were included in the study. Triglyceride (TG), total cholesterol (TC), HDL-C, LDL-C, apolipoproteins (apo) A-I and B, glucose and insulin levels were quantified. Lipid indexes and HOMA-IR were calculated. Cholesterol efflux (CEC), lipoprotein associated phospholipase A (Lp-PLA), lecithin-cholesterol acyl transferase (LCAT) and cholesteryl ester transfer protein, plus paraoxonase and arylesterase (ARE) activities were evaluated. Obese children and adolescents showed significantly higher TG [69 (45-95) vs 96 (76-121); p < 0.05], non-HDL-C [99 ± 34 vs 128 ± 26; p < 0.01], TC/HDL-C [2.8 ± 0.6 vs 4.7 ± 1.5; p < 0.01], TG/HDL-C [1.1 (1.0-1.8) vs 2,2 (1.4-3.2); p < 0.01], and HOMA-IR [1.5 (1.1-1.9) vs. 2.6 (2.0-4.5); p < 0.01] values, plus Lp-PLA activity [8.3 ± 1.9 vs 7.1 ± 1.7 umol/ml.h; p < 0,05] in addition to lower HDL-C [57 ± 10 vs 39 ± 9; p < 0.01], apo A-I [143 ± 25 vs 125 ± 19; p < 0.05], and CEC [6.4 (5.1-6.8) vs. 7.8 (5.7-9.5); p < 0.01] plus LCAT [12.6 ± 3.3 vs 18.7 ± 2.6; p < 0.05] and ARE [96 ± 19 vs. 110 ± 19; p < 0.05] activities. Lp-PLA activity correlated with LDL-C (r = 0.72,p < 0.01), non-HDL-C (r = 0.76,p < 0.01), and apo B (r = 0.60,p < 0.01). LCAT activity correlated with triglycerides (r = -0.78,p < 0.01), HDL-C (r = 0.64,p < 0.01), and apo A-I (r = 0.62, p < 0.05). ARE activity correlated with HDL-C (r = 0.32,p < 0.05) and apoA-I (r = 0.43,p < 0.01). CEC was negatively associated with BMI z-score (r = -0.36,p < 0.05), and triglycerides (r = -0.28,p < 0.05), and positively with LCAT activity (r = 0.65,p < 0.05). In multivariate analysis, BMI z-score was the only parameter significantly associated to CEC (r2 = 0.43, beta = -0.38, p < 0.05).

CONCLUSION

The obese group showed alterations in carbohydrate and lipid metabolism, which were associated to the presence of vascular specific inflammation and impairment of HDL atheroprotective capacity. These children and adolescents would present qualitative alterations in their lipoproteins which would determine higher risk of suffering premature cardiovascular disease.

摘要

背景和目的

儿童肥胖与胰岛素抵抗和血脂异常等并发症有关。高密度脂蛋白(HDL)是唯一具有抗动脉粥样硬化特性的脂蛋白。本研究旨在分析肥胖儿童和青少年与健康对照组相比的炎症标志物、碳水化合物代谢、血脂谱和 HDL 功能。

方法和结果

研究纳入了 20 名肥胖儿童和青少年(体重指数 z 评分>3.0)(9-15 岁)和 20 名年龄和性别相匹配的对照组。定量测定了甘油三酯(TG)、总胆固醇(TC)、HDL-C、LDL-C、载脂蛋白(apo)A-I 和 B、血糖和胰岛素水平。计算了血脂指数和 HOMA-IR。评估了胆固醇流出(CEC)、脂蛋白相关磷脂酶 A(Lp-PLA)、卵磷脂胆固醇酰基转移酶(LCAT)和胆固醇酯转移蛋白,以及对氧磷酶和芳基酯酶(ARE)活性。肥胖儿童和青少年的 TG[69(45-95)比 96(76-121);p<0.05]、非 HDL-C[99±34 比 128±26;p<0.01]、TC/HDL-C[2.8±0.6 比 4.7±1.5;p<0.01]、TG/HDL-C[1.1(1.0-1.8)比 2.2(1.4-3.2);p<0.01]和 HOMA-IR[1.5(1.1-1.9)比 2.6(2.0-4.5);p<0.01]值更高,Lp-PLA 活性[8.3±1.9 比 7.1±1.7 umol/ml.h;p<0.05],以及 HDL-C[57±10 比 39±9;p<0.01]、apo A-I[143±25 比 125±19;p<0.05]和 CEC[6.4(5.1-6.8)比 7.8(5.7-9.5);p<0.01]、LCAT[12.6±3.3 比 18.7±2.6;p<0.05]和 ARE[96±19 比 110±19;p<0.05]活性降低。Lp-PLA 活性与 LDL-C(r=0.72,p<0.01)、非 HDL-C(r=0.76,p<0.01)和 apo B(r=0.60,p<0.01)相关。LCAT 活性与甘油三酯(r=-0.78,p<0.01)、HDL-C(r=0.64,p<0.01)和 apo A-I(r=0.62,p<0.05)相关。ARE 活性与 HDL-C(r=0.32,p<0.05)和 apoA-I(r=0.43,p<0.01)相关。CEC 与 BMI z 评分(r=-0.36,p<0.05)和甘油三酯(r=-0.28,p<0.05)呈负相关,与 LCAT 活性呈正相关(r=0.65,p<0.05)。多元分析显示,BMI z 评分是唯一与 CEC 显著相关的参数(r2=0.43,beta=-0.38,p<0.05)。

结论

肥胖组表现出碳水化合物和脂质代谢的改变,这与血管特异性炎症和 HDL 抗动脉粥样硬化能力受损有关。这些儿童和青少年的脂蛋白可能存在质量改变,这将导致他们患早发性心血管疾病的风险增加。

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