运动对肥胖儿童少年糖脂代谢和内脂素的影响及内脂素基因多态性研究
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摘要
一、研究目的与意义:
儿童少年肥胖与糖脂代谢紊乱密切相关,目前缺乏运动对肥胖儿童少年红细胞膜脂质、血糖脂代谢及内源性调节因素等影响的系统研究。
本研究分析了4周封闭式中小强度长时间有氧运动减肥干预前后不同肥胖程度儿童少年血糖、血脂、红细胞膜脂质的变化,以新型脂肪细胞因子内脂素为主线,研究其结合瘦素、IL-6等内源性调节因素在运动干预下对肥胖儿童少年糖脂代谢的调节,并探索内脂素基因多态性(SNPs)和糖脂代谢水平的关联及其对运动减肥效果的影响,为探讨运动减肥机制、指导运动减肥提供科学的理论依据。
二、研究内容与结果:
研究共包括四个部分7个实验。
第一部分(实验1)比较了BIA法和皮褶厚度法的五种推导公式(Brozek公式、Siri公式、Lohman公式、Slaughter公式、国内儿童少年常用公式)对本研究所涉及的88名肥胖儿童少年体脂率的预测结果,发现相对于皮褶厚度法,BIA法所测得的体脂率较符合本研究实际测量条件和所测人群特点,可按该方法所测得的体脂百分比将本研究对象分为轻度、中度和重度肥胖组。体脂率间接评价方法的确定为本篇后续研究提供了必要的前提。
第二部分(实验2、3)对肥胖儿童少年运动干预前后血糖血脂、膜脂及相关ATP酶活性的变化进行探讨,主要结果如下:①运动干预前轻度肥胖组红细胞膜磷脂酰丝氨酸(PS)外翻与其他两组存在显著性差异,血HDL仅在轻度和重度组之间存在显著性差异(P≤0.05);②运动干预后BMI、体脂率、WHR等形态指标显著性下降,各项血糖血脂指标及膜Na+K+-ATPase活性也均呈显著性改善,而膜PS外翻虽有所下降,但无显著性意义;③运动前血糖脂代谢指标与身体形态尤其是WC相关显著,且运动引起的体脂率变化也与血脂指标变化显著相关。
第三部分(实验4、5)探讨运动干预前下内脂素结合瘦素、IL-6等内源性调节因素对肥胖儿童少年糖脂代谢的调节,主要结果如下:①运动前血内脂素与HDL显著正相关,而与糖代谢指标无显著性相关;②运动前血内脂素与瘦素、IL-6等显著相关,运动后血内脂素水平与瘦素水平显著上升,运动引起的二者变化值呈强相关(R=1,P=.000);③运动后不同肥胖组间内脂素的上升幅度与形态指标、糖代谢指标的下降幅度相一致。
第四部分(实验6、7)采用LDR-PCR测序分型技术,探讨内脂素RS5974456、RS4730153位点SNPs对肥胖儿童少年运动干预前后糖脂代谢及其他肥胖相关变量的影响。主要结果如下:①RS4730153位点A/G基因分型为14例(男性8名,女性6名),频率为15.9%,而RS5974456 G/T基因变异型仅出现1例(男性);②运动前RS4730153 AG型人群血TG水平显著高于GG型,运动干预下GG基因型△HOMA-β显著大于AG型。
三、研究结论:
1、肥胖尤其是腹部肥胖与儿童少年血脂异常和胰岛素敏感性降低密切相关,在脂代谢紊乱的初期,红细胞膜脂质变化可能比血脂指标更能体现儿童少年肥胖的发展;
2、有氧运动干预不仅能有效降低肥胖儿童少年体脂总量及体内脂肪的分布,而且能通过改善红细胞膜Na+K+-ATPase活性、胰岛素敏感性、内脂素等脂肪细胞因子水平等方面对糖脂代谢进行调节,但红细胞膜脂质的改善滞后于血脂的改善;
3、肥胖儿童少年内脂素与其他脂肪细胞因子尤其是瘦素水平存在明显关联,共同实现对运动干预下肥胖儿童少年糖脂代谢的调节;
4、中国汉族肥胖儿童少年中存在内脂素SNPs位点RS4730153变异,纯合子GG型可能可以通过降低TG水平、提高胰岛素β细胞功能对运动干预的敏感性等方面参与肥胖儿童少年的糖脂代谢调节。
一、The Purpose and Significance of Research
Obesity is closely related to glucose and lipid metabolism disorders in children and adolescents.At present,a systemic research about the exercise-induced changes of glucose and lipid metabolism,erythrocyte membrane lipids and endogenous regulator in obese children and adolescents is lacked.
In this research the changes of Plasmaglucose, Plasmalipids and erythrocyte membrane lipids of different obesity degrees children and adolescents before and after a 4-week closed aerobic exercise to lose weight with small and medium intensity and long term time were analyzed. Visfatin,a new adipocytokine,being the main line in this research,the regulation of it combined endogenous regulators such as leptin,IL-6 to the exercise-induced changes of glucose and lipid metabolism in obese children and adolescents was studied.Meanwhile,the association between visfatin SNPs and levels of glucose and lipid metabolism was investigated.This research was designed to provide a scientific theory foundation for exploring the mechanism of exercise to lose weight .
二、The Contents and Experimental Results of Research
The whole study is composed of four parts with seven experiments.
The first part(experiment 1) is to study comparatively six different indirect evaluation of body fat ,and try to find out a relatively appropriate indirect method to estimate body fat mass in 88 obese children and adolescents involved in this research.Pearson correlation and Multiple Stepwise regression analysis were applied to compare the results among BIA,Lohman,,Brozek,,Siri,,Slaughter,and Chinese prediction equations.The results showed that compared to the prediction equations through various types of skin fold thickness,it seemed that BIA could be more accurately used to estimate body fat mass in obese children and adolescents in this research. According to percentage of body fat measured by BIA,88 obese children and adolescents were divided into mild, moderate and severe obesity group.The determination of indirect evaluation method of body fat rate provided a necessary premise for the follow-up study in this research.
The second part study(experiment 2,3) focused on the influence of exercise-induced weight loss on plasmaglucose,plasmalipid,erythrocyte membrane lipid and related ATPase activity in obese children and adolescents.The main results were as follows:①PS exposure was significantly higher in the severe obesity group than in the other two groups(P≤0.05),while plasma level of HDL was significantly different only between the mild obesity group and the severe one.②A significant increase in Na+K+-ATPase activity after exercise intervention(P≤0.05) while no significant increase in Ca2+Mg2+-ATPase activity.A downward trend in PS exposure on erythrocyte membrane after exercise intervention was observed but there was no significant difference.③plasmaglucose and lipids index were correlated to the indicators of human morphology especially WC before exercise intervention,and exercise-induced changes in body fat rate was also significantly correlated to the changes in plasmalipids.
The third part study(experiment 4,5) focused on the regulation of visfatin combined endogenous regulators such as leptin,IL-6 to the exercise-induced changes of glucose and lipid metabolism in obese children and adolescents.The main results were as follows:①Pre-exercise plasma visfatin was significantly positively correlated with HDL,while no significant correlation with glucose metabolism.②Pre-exercise plasma visfatin was significantly positively correlated with other adipocytokines such as leptin and IL-6. The significantly increase of exercise-induced plasma visfatin was positively correlated with that of leptin.③The rise margin of visfatin was consistent to the decline margin of human morphology indicators and glucose metabolism among the different obese groups.
The fourth part study(experiment 4,5) focused on investigating the single nucleotide polymorphisms(SNPs) of RS5974456 and RS4730153 in visfatin gene in obese children and adolescents of Han population,and analyzing its relation to the exercise-induced glucose ,lipid metabolism and obesity-related variables changes. The main results were as follows:①14 obese children and adolescents were visfatin RS4730153 A/G genotype and the frequencies was 15.9%,but only one was RS5974456 G/T genotype.②The indexes of glucose and lipid metabolism before and after aerobic exercise showed significant changes.TG levels before exercise was significantly different between the different genotypes subjects(GG: 1.40±0.74mmol / L,AG: 1.86±1.11mmol / L,respectively.P =. 050).HOMA-βafter exercise was significantly different between the different genotypes subjects(GG: 220.50±178.81, AG: 332.23±207.90,respectively.P =. 050).
三、Conclusion:
①Obesity,especially abdominal obesity in children and adolescents is closely related to dyslipidemia and reduced insulin sensitivity.The abnormal PS exposure maybe take place earlier than the change in plasma lipids.
②Aerobic exercise intervention can not only reduce the total amount and distribution of body fat in obese children and adolescents,but also regulate glucose and lipid metabolism through the improvement of erythrocyte membrane Na+K+-ATPase activity, insulin sensitivity, adipocytokine level such as visfatin.However,the improvement of erythrocyte membrane lipids lags to that of plasmalipids.
③A strong correlation exists between visfatin and other adipocytokine especially leptin to achieve the regulation of glucose and lipid metabolism under the intervention of exercise in obese children and adolescent.
④The SNPs of visfatin RS4730153 variation was found in obesity children and adolescents from Chinese Han population.Homozygous GG was possibly involved in glucose and lipid metabolism by reducing TG levels and improving exercise-induced HOMA-βsensitivity.
儿童少年肥胖与糖脂代谢紊乱密切相关,目前缺乏运动对肥胖儿童少年红细胞膜脂质、血糖脂代谢及内源性调节因素等影响的系统研究。
本研究分析了4周封闭式中小强度长时间有氧运动减肥干预前后不同肥胖程度儿童少年血糖、血脂、红细胞膜脂质的变化,以新型脂肪细胞因子内脂素为主线,研究其结合瘦素、IL-6等内源性调节因素在运动干预下对肥胖儿童少年糖脂代谢的调节,并探索内脂素基因多态性(SNPs)和糖脂代谢水平的关联及其对运动减肥效果的影响,为探讨运动减肥机制、指导运动减肥提供科学的理论依据。
二、研究内容与结果:
研究共包括四个部分7个实验。
第一部分(实验1)比较了BIA法和皮褶厚度法的五种推导公式(Brozek公式、Siri公式、Lohman公式、Slaughter公式、国内儿童少年常用公式)对本研究所涉及的88名肥胖儿童少年体脂率的预测结果,发现相对于皮褶厚度法,BIA法所测得的体脂率较符合本研究实际测量条件和所测人群特点,可按该方法所测得的体脂百分比将本研究对象分为轻度、中度和重度肥胖组。体脂率间接评价方法的确定为本篇后续研究提供了必要的前提。
第二部分(实验2、3)对肥胖儿童少年运动干预前后血糖血脂、膜脂及相关ATP酶活性的变化进行探讨,主要结果如下:①运动干预前轻度肥胖组红细胞膜磷脂酰丝氨酸(PS)外翻与其他两组存在显著性差异,血HDL仅在轻度和重度组之间存在显著性差异(P≤0.05);②运动干预后BMI、体脂率、WHR等形态指标显著性下降,各项血糖血脂指标及膜Na+K+-ATPase活性也均呈显著性改善,而膜PS外翻虽有所下降,但无显著性意义;③运动前血糖脂代谢指标与身体形态尤其是WC相关显著,且运动引起的体脂率变化也与血脂指标变化显著相关。
第三部分(实验4、5)探讨运动干预前下内脂素结合瘦素、IL-6等内源性调节因素对肥胖儿童少年糖脂代谢的调节,主要结果如下:①运动前血内脂素与HDL显著正相关,而与糖代谢指标无显著性相关;②运动前血内脂素与瘦素、IL-6等显著相关,运动后血内脂素水平与瘦素水平显著上升,运动引起的二者变化值呈强相关(R=1,P=.000);③运动后不同肥胖组间内脂素的上升幅度与形态指标、糖代谢指标的下降幅度相一致。
第四部分(实验6、7)采用LDR-PCR测序分型技术,探讨内脂素RS5974456、RS4730153位点SNPs对肥胖儿童少年运动干预前后糖脂代谢及其他肥胖相关变量的影响。主要结果如下:①RS4730153位点A/G基因分型为14例(男性8名,女性6名),频率为15.9%,而RS5974456 G/T基因变异型仅出现1例(男性);②运动前RS4730153 AG型人群血TG水平显著高于GG型,运动干预下GG基因型△HOMA-β显著大于AG型。
三、研究结论:
1、肥胖尤其是腹部肥胖与儿童少年血脂异常和胰岛素敏感性降低密切相关,在脂代谢紊乱的初期,红细胞膜脂质变化可能比血脂指标更能体现儿童少年肥胖的发展;
2、有氧运动干预不仅能有效降低肥胖儿童少年体脂总量及体内脂肪的分布,而且能通过改善红细胞膜Na+K+-ATPase活性、胰岛素敏感性、内脂素等脂肪细胞因子水平等方面对糖脂代谢进行调节,但红细胞膜脂质的改善滞后于血脂的改善;
3、肥胖儿童少年内脂素与其他脂肪细胞因子尤其是瘦素水平存在明显关联,共同实现对运动干预下肥胖儿童少年糖脂代谢的调节;
4、中国汉族肥胖儿童少年中存在内脂素SNPs位点RS4730153变异,纯合子GG型可能可以通过降低TG水平、提高胰岛素β细胞功能对运动干预的敏感性等方面参与肥胖儿童少年的糖脂代谢调节。
一、The Purpose and Significance of Research
Obesity is closely related to glucose and lipid metabolism disorders in children and adolescents.At present,a systemic research about the exercise-induced changes of glucose and lipid metabolism,erythrocyte membrane lipids and endogenous regulator in obese children and adolescents is lacked.
In this research the changes of Plasmaglucose, Plasmalipids and erythrocyte membrane lipids of different obesity degrees children and adolescents before and after a 4-week closed aerobic exercise to lose weight with small and medium intensity and long term time were analyzed. Visfatin,a new adipocytokine,being the main line in this research,the regulation of it combined endogenous regulators such as leptin,IL-6 to the exercise-induced changes of glucose and lipid metabolism in obese children and adolescents was studied.Meanwhile,the association between visfatin SNPs and levels of glucose and lipid metabolism was investigated.This research was designed to provide a scientific theory foundation for exploring the mechanism of exercise to lose weight .
二、The Contents and Experimental Results of Research
The whole study is composed of four parts with seven experiments.
The first part(experiment 1) is to study comparatively six different indirect evaluation of body fat ,and try to find out a relatively appropriate indirect method to estimate body fat mass in 88 obese children and adolescents involved in this research.Pearson correlation and Multiple Stepwise regression analysis were applied to compare the results among BIA,Lohman,,Brozek,,Siri,,Slaughter,and Chinese prediction equations.The results showed that compared to the prediction equations through various types of skin fold thickness,it seemed that BIA could be more accurately used to estimate body fat mass in obese children and adolescents in this research. According to percentage of body fat measured by BIA,88 obese children and adolescents were divided into mild, moderate and severe obesity group.The determination of indirect evaluation method of body fat rate provided a necessary premise for the follow-up study in this research.
The second part study(experiment 2,3) focused on the influence of exercise-induced weight loss on plasmaglucose,plasmalipid,erythrocyte membrane lipid and related ATPase activity in obese children and adolescents.The main results were as follows:①PS exposure was significantly higher in the severe obesity group than in the other two groups(P≤0.05),while plasma level of HDL was significantly different only between the mild obesity group and the severe one.②A significant increase in Na+K+-ATPase activity after exercise intervention(P≤0.05) while no significant increase in Ca2+Mg2+-ATPase activity.A downward trend in PS exposure on erythrocyte membrane after exercise intervention was observed but there was no significant difference.③plasmaglucose and lipids index were correlated to the indicators of human morphology especially WC before exercise intervention,and exercise-induced changes in body fat rate was also significantly correlated to the changes in plasmalipids.
The third part study(experiment 4,5) focused on the regulation of visfatin combined endogenous regulators such as leptin,IL-6 to the exercise-induced changes of glucose and lipid metabolism in obese children and adolescents.The main results were as follows:①Pre-exercise plasma visfatin was significantly positively correlated with HDL,while no significant correlation with glucose metabolism.②Pre-exercise plasma visfatin was significantly positively correlated with other adipocytokines such as leptin and IL-6. The significantly increase of exercise-induced plasma visfatin was positively correlated with that of leptin.③The rise margin of visfatin was consistent to the decline margin of human morphology indicators and glucose metabolism among the different obese groups.
The fourth part study(experiment 4,5) focused on investigating the single nucleotide polymorphisms(SNPs) of RS5974456 and RS4730153 in visfatin gene in obese children and adolescents of Han population,and analyzing its relation to the exercise-induced glucose ,lipid metabolism and obesity-related variables changes. The main results were as follows:①14 obese children and adolescents were visfatin RS4730153 A/G genotype and the frequencies was 15.9%,but only one was RS5974456 G/T genotype.②The indexes of glucose and lipid metabolism before and after aerobic exercise showed significant changes.TG levels before exercise was significantly different between the different genotypes subjects(GG: 1.40±0.74mmol / L,AG: 1.86±1.11mmol / L,respectively.P =. 050).HOMA-βafter exercise was significantly different between the different genotypes subjects(GG: 220.50±178.81, AG: 332.23±207.90,respectively.P =. 050).
三、Conclusion:
①Obesity,especially abdominal obesity in children and adolescents is closely related to dyslipidemia and reduced insulin sensitivity.The abnormal PS exposure maybe take place earlier than the change in plasma lipids.
②Aerobic exercise intervention can not only reduce the total amount and distribution of body fat in obese children and adolescents,but also regulate glucose and lipid metabolism through the improvement of erythrocyte membrane Na+K+-ATPase activity, insulin sensitivity, adipocytokine level such as visfatin.However,the improvement of erythrocyte membrane lipids lags to that of plasmalipids.
③A strong correlation exists between visfatin and other adipocytokine especially leptin to achieve the regulation of glucose and lipid metabolism under the intervention of exercise in obese children and adolescent.
④The SNPs of visfatin RS4730153 variation was found in obesity children and adolescents from Chinese Han population.Homozygous GG was possibly involved in glucose and lipid metabolism by reducing TG levels and improving exercise-induced HOMA-βsensitivity.
引文
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