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脂蛋白脂肪酶(LPL)基因rs283多态性对肥胖青少年运动诱导的代谢变化的影响及其背后的调控机制。

Impact of LPL gene rs283 polymorphism on exercise-induced changes in metabolism of obese adolescents and the regulatory mechanisms behind it.

作者信息

Gao Rui-Rui, Wang Min, Hu Yang, Xu Chun-Yan, Li Yan-Chun, Zhang Ze-Ya, Chen Si-Yun, Mao Xiao-Yun

机构信息

Science and Research Center, Beijing Sport University, Beijing, China.

Department of Foreign Languages, Beijing Sport University, Beijing, China.

出版信息

Exp Physiol. 2015 Jun;100(6):698-707. doi: 10.1113/EP085127.

DOI:10.1113/EP085127
PMID:25809647
Abstract

What is the central question of this study? We investigated whether the LPL gene rs283 polymorphism affects exercise-induced changes in body composition and lipid and glucose metabolism in obese adolescents and whether it is functional. What is the main finding and its importance? Chinese obese adolescents of Han nationality with the GG genotype of the rs283 polymorphism were more sensitive to exercise-induced reduction of the body fat percentage, insulin resistance and plasma triglyceride levels. The G allele can significantly increase reporter gene expression level, which may be the molecular reason for the difference in exercise-induced parameter changes among obese adolescents. The aim of this investigation was to explore the association between the rs283 polymorphism located in the lipoprotein lipase (LPL) gene and exercise-induced changes in body composition and lipid and glucose metabolism in obese adolescents and to probe into the molecular regulatory mechanisms. Fifty-five obese adolescents of Han nationality underwent aerobic training for 4 weeks. Body composition and lipid and glucose metabolic parameters were tested before and after the training. The rs283 polymorphism was genotyped by PCR-restriction fragment length polymorphism, and association analysis with the weight-reducing effect was performed. The regulatory mechanisms of the rs283 polymorphism were explored through the dual-luciferase reporter assay. Exercise-induced change rates were as follows: the change in body fat percentage of GG genotype groups was 3.37 ± 1.60, significantly higher than that of GA genotype groups (2.09 ± 1.53, P < 0.01); the change in the homeostasis model assessment of insulin resistance was 0.52 ± 0.13, obviously higher than that of GA genotype groups (0.44 ± 0.10, P < 0.05); and the change in triglyceride was 51.91 ± 6.56, much higher than that of GA genotype groups (47.06 ± 5.36, P < 0.01). The relative luciferase activity of the reporter gene in recombinant vector carrying the G allele was 2.67 ± 0.22, markedly higher than that in recombinant vector carrying the A allele (1.63 ± 0.03, P < 0.01). Chinese obese adolescents of Han nationality with GG genotype of the rs283 polymorphism were more sensitive to exercise-induced parameter changes. The G allele can improve reporter gene expression level, indicating the effects of rs283 on gene expression.

摘要

本研究的核心问题是什么?我们调查了脂蛋白脂肪酶(LPL)基因rs283多态性是否影响肥胖青少年运动诱导的身体成分、脂质和葡萄糖代谢变化,以及它是否具有功能性。主要发现及其重要性是什么?rs283多态性GG基因型的中国汉族肥胖青少年对运动诱导的体脂百分比降低、胰岛素抵抗和血浆甘油三酯水平变化更敏感。G等位基因可显著提高报告基因表达水平,这可能是肥胖青少年运动诱导参数变化存在差异的分子原因。本研究旨在探讨脂蛋白脂肪酶(LPL)基因中rs283多态性与肥胖青少年运动诱导的身体成分、脂质和葡萄糖代谢变化之间的关联,并探究其分子调控机制。55名汉族肥胖青少年进行了为期4周的有氧训练。在训练前后测试身体成分、脂质和葡萄糖代谢参数。通过聚合酶链反应-限制性片段长度多态性对rs283多态性进行基因分型,并进行与减肥效果的关联分析。通过双荧光素酶报告基因检测探究rs283多态性的调控机制。运动诱导的变化率如下:GG基因型组的体脂百分比变化为3.37±1.60,显著高于GA基因型组(2.09±1.53,P<0.01);胰岛素抵抗稳态模型评估变化为0.52±0.13,明显高于GA基因型组(0.44±0.10,P<0.05);甘油三酯变化为51.91±6.56,远高于GA基因型组(47.06±5.36,P<0.01)。携带G等位基因的重组载体中报告基因的相对荧光素酶活性为2.67±0.22,显著高于携带A等位基因的重组载体(1.63±0.03,P<0.01)。rs283多态性GG基因型的中国汉族肥胖青少年对运动诱导的参数变化更敏感。G等位基因可提高报告基因表达水平,表明rs283对基因表达有影响。

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