青春期肥胖儿童血清瘦素、脂联素与代谢综合征的关系
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摘要
肥胖(obesity)是在遗传和环境因素的作用下,机体的能量摄入量大于消耗量,能量以脂肪形式储存在体内,以致于使体重过度增加所引起的营养失衡性疾病。肥胖已成为一种全球的流行病。肥胖者发生糖尿病和心血管疾病的危险性增高。代谢综合征(metabolic syndrome,MS)指一系列代谢紊乱在同一个体聚集的现象,包括:腹型肥胖,血脂紊乱,糖调节异常和高血压。代谢综合征是糖尿病和心血管病的危险因素之一。美国国家健康与营养第三次调查(NHNESⅢ)(1988～1994年)数据显示,12～19岁总人群MS患病率为4.2%,超重、肥胖人群分别为6.8%和28.7%,而正常体重人群仅0.1%。虽然代谢综合征的发病机理目前还不清楚,很明显肥胖是代谢综合征的危险因素之一。
脂肪组织不仅可以贮存能量,也可以分泌多种有生物活性的脂肪因子。瘦素(leptin,LEP)和脂联素(adiponectin,ADIPO)即是由脂肪细胞分泌的脂肪因子。ob/ob小鼠由于瘦素缺乏表现为肥胖,给予外源性瘦素后,进食减少,能量消耗增加,体重逐渐降低;随后的研究发现大多数肥胖者血液中瘦素含量与正常体重者相比是升高的,但并没有出现体重下降。研究显示瘦素可作用于脂肪、肌肉、肝脏、血管等外周组织,参与脂质代谢、血压调节,可能和代谢综合征的发生有关。脂联素是由脂肪细胞分泌的脂肪因子,和同样是脂肪因子的瘦素不同,脂联素在肥胖者血液中相对于体重正常者是降低的。目前研究显示其参与糖、脂代谢的调节,增加胰岛素的敏感性,可能和代谢综合征的发生有关。
瘦素、脂联素是否为代谢综合征的病因目前还不清楚。在瘦素、脂联素与代谢综合征组分的相关性研究中结论很不一致。青春期是儿童期肥胖发生率较高的时期,青春期肥胖亦易延续为成年肥胖,且儿童较成年人少并发糖尿病、心血管疾病,更易把瘦素、脂联素与代谢综合征组分的相关性表现出来。本研究以青春期儿童为研究对象,探讨瘦素、脂联素与代谢综合征的关系,为代谢综合征的发病机制研究和早期防治提供理论依据。
目的
1了解在肥胖儿童体内血糖、血脂、血压、瘦素、脂联素水平变化。
2探讨瘦素、脂联素与代谢综合征的关系。
对象与方法
共选取13～15岁青春期儿童177名,肥胖86人,男45人,女41人;体重正常者91人,男51人,女40人。测量身高(height)、体重(weight)、腰围(waistcircumference,WC)、臀围(hip circumference)、收缩压(systolic blood pressure,SBP)和舒张压(diastolic blood pressure,DBP),计算身体质量指数(body mass index,BMI)和腰臀比(waist-to-hip ratio,WHR)。抽取晨起空腹静脉血,测定血糖(glucose,GLU)、血甘油三酯(triglyceride,TG)和高密度脂蛋白胆固醇(High-density-lipoprotein-cholesterol,HDL-C),用放射免疫分析法(radioimmunoassay,RIA)测定血清胰岛素(insulin,INS)和瘦素,用酶联免疫吸附试验(enzymelinked immunosorbent assay,ELISA)测定血清脂联素。代谢综合征的诊断采用修正的美国学者Cook提出青少年人群MS诊断标准。数值变量均数比较用t检验和单因素方差分析,两变量相关分析用pearson相关和偏相关分析,分类变量进行χ~2检验,用logistic回归进行肥胖儿童代谢综合征危险因素分析。
结果
1男肥胖组甘油三酯、收缩压、胰岛素、瘦素平均水平高于正常体重组,高密度脂蛋白胆固醇、脂联素平均水平低于正常体重组(TG:1.74±0.91mmol/l和0.76±0.22mmol/l:SBP:123.60±14.11mmHg和111.38±10.18 mmHg;INS:28.72±13.79mIU/l和16.74±6.53 mIU/l;LEP:19.49±6.94μg/l和8.08±4.15μg/l;HDL-C:1.07±0.25mmol/l和1.36±0.33mmol/l;ADIPO:3.50±1.50mg/l和5.28±2.68mg/l,P均＜0.05)。女肥胖组甘油三酯、收缩压、舒张压、胰岛素、瘦素水平高于体重正常组,高密度脂蛋白胆固醇、脂联素水平低于体重正常组(TG:1.43±0.64mmol/l和0.91±0.25mmol/l;SBP:115.48±10.47mmHg和105.95±9.71mmHg;DBP:73.73±8.84和66.53±8.53;INS:24.51±10.93 mIU/l和17.12±5.45mIU/l;LEP:27.55±4.23μg/l和17.93±5.08μg/l:HDL-C:1.13±0.23mmol/l和1.48±0.33mmol/l;ADIPO:4.66±3.06mg/l和6.33±3.64mg/l,P均＜0.05)。肥胖儿童代谢综合征检出率30.23%,高于体重正常儿童(P＜0.01)。
2血清瘦素水平肥胖组和体重正常组男性均低于女性(肥胖组:19.49±6.9μg/l和27.55±4.23μg/l,对照组:8.08±4.15μg/l和17.93±5.08μg/l,P均＜0.01);血清脂联素水平肥胖组和体重正常组男性也均低于女性(肥胖组:3.50±1.50 mg/l和4.66±3.06 mg/l,对照组:5.28±2.68 mg/l和6.33±3.64 mg/l,P均＜0.05)。
3瘦素与BMI、腰围、胰岛素、甘油三酯、收缩压呈正相关(BMI:男r=0.722,女r=0.812;WC:男r=0.778,女r=0.796;INS:男r=0.625,女r=0.438;TG:男r=0.576,女r=0.389;SBP:男r=0.415,女r=0.359,P均＜0.05),瘦素和女性舒张压呈正相关(r=0.395,P＜0.05),瘦素与高密度脂蛋白胆固醇均呈负相关(男r=-0.347和女r=-0.535,P＜0.05);控制BMI后,瘦素仅和男性胰岛素有正相关(偏相关系数=0.402,P＜0.05),与男女甘油三酯、高密度脂蛋白胆固醇、收缩压、舒张压均无相关性(P＞0.05)。
4脂联素与BMI、腰围、胰岛素、甘油三酯呈负相关(BMI:男r=-0.350,女r=-0.299;WC:男r=-0.405,女r=-0.317;INS:男r=-0.232,女r=-0.327;TG:男r=-0.301,女r=-0.240,P＜0.05),与高密度脂蛋白胆固醇呈正相关(男r=0.251,女r=0.260,P＜0.05);控BMI后,脂联素与甘油三酯、高密度脂蛋白胆固醇、胰岛素均无相关性(P＞0.05)。
5 BMI与甘油三酯、收缩压、舒张压、胰岛素呈正相关(TG:男r=0.664,女r=509;SBP:男r=0.532,女r=0.562;DBP:男r=0.24,女r=0.513;INS:男r=0.504,女r=0.545,P＜0.05),和高密度脂蛋白胆固醇呈负相关(男r=-0.419,女r=-0.599,P＜0.05);控制瘦素、脂联素进行偏相关分析,BMI与甘油三酯、收缩压、舒张压、高密度脂蛋白胆固醇仍有相关(TG:男偏相关系数=0.407,女偏相关系数=0.364;SBP:男偏相关系数=0.368,女偏相关系数=0.509;DBP:男偏相关系数=0.218,女偏相关系数=0.393:HDL-C:男偏相关系数=-0.259,女偏相关系数=-0.337,P均＜0.05)。控制瘦素后进行偏相关分析,女BMI与胰岛素有相关性(偏相关系数=0.435,P＜0.05),男BMI与胰岛素无相关性(P＞0.05)。
6肥胖儿童代谢综合征危险因素logistic回归分析显示,BMI、胰岛素是肥胖儿童发生代谢综合征的危险因素(BMI:OR=1.974;INS:OR=1.884,P＜0.05)。
结论
1青春期肥胖儿童中存在脂代谢异常,血压升高,血清瘦素、胰岛素水平增高和脂联素水平降低,肥胖儿童代谢综合征检出率增高。
2青春期儿童血清瘦素与甘油三酯、收缩压、舒张压呈正相关,与高密度脂蛋白胆固醇呈负相关;脂联素与甘油三酯呈负相关,高密度脂蛋白胆固醇呈正相关;对于肥胖儿童,血清瘦素升高、脂联素降低可能和其代谢综合征发生率较高有关。
3血清瘦素与胰岛素水平呈正相关;瘦素可能是引起青春期男性儿童血清胰岛素升高的主要因素之一。
4肥胖程度、空腹血清胰岛素水平是肥胖儿童发生代谢综合征的危险因素。
Obesity is a kind of nutritional imbalance disease caused by intaking more energy than consumption under the genetic and environmental factors, and has become a worldwide epidemic. Obesity can result in all kinds of chronic diseases such as diabetes mellitus and cardiovascular disease. Metabolic Syndrome(MS) is a new concept developmented recently. It refers to a series of metabolic disorders in identical individual, including dyslipidemia, abdominal obesity, elevated blood pressure, and impaired glucose tolerance. And MS is a risk factor of cardiovascular disease and type 2 diabetes. The existing epidemiological investigations showed the prevalence of MS is higher in obese population than that of the normal weignt population. Obesity can contribute to the incidence of metabolic syndrome obviously although its underlying pathophysiology is unclear.
Adipose tissue can not only store energy, but also secrete a variety of bioactive substances. Leptin(LEP) and adiponectin(ADIPO) are two adipokines secreted by adipocytes. The main physiological function of leptin can act on the hypothalamus and reduce food intake and increase energy expenditure, at last result in weight loss. The level of leptin is higher in obese bosy compared with the normal. Recent studies show that leptin may also act in peripheral tissues, such as adipose tissue, muscle, liver, and so on. And it is involved in blood pressure regulation and lipid metabolism. So leptin may be a risk factor of MS. Adiponecein is another adipose tissue-specific adipokine. However plasma Adiponecein level is lower in obese individual than that of normal . Adiponecein has many biofunctions, including the regulation of blood glucose and lipids, adiponecein can alao improve the sensitivity of insulin. So low adiponecein level may be a risk factor of MS.
To date, the relatipnship of leptin, adiponectin and MS is unclear. The incidence of obesity and MS is higher and obesity-related complications are less in adolescents than that in adults. The study was designed to explore the relationship between leptin, adiponecein and MS in adolescents to provide a therotical basis for further research.
Objectives
1 To understand the changes of blood pressure and plasma level of lipids, blood glucose, leptin and adiponecein.
2 To explore the relationship of serum leptin, adiponecein and MS.
Subjects and Methods
We enrolled 86 obese(male: 45, female: 41)and 91 weight normal (boy: 51, girl: 40) adolescents aged 13～15years. Height, weight, waist circumference(WC), hip circumference, systolic blood pressure (SBP) and diastolic blood pressure(DBP)were measured, body mass index(BMI) and waist-hip ratio(WHR) were calculated. Morning fasting venous blood samples were collected and blood glucose(GLU), blood triglyceride(TG), high-density-lipoprotein-cholesterol(HDL-C) were measured. Serum insulin and leptin were measured by radioimmunoassay(RIA), and serum adiponectin were measured by enzymelinked immunosorbent assay(ELISA). MS was defined according to the modified Cook's definition. Numerical variables were compared using one-sample T test and one-way ANOVA, Correlation of variables was evaluated using Pearson's correlation coefficient and partial correlation coefficient. Classification variables were tested using X~2 test and logistic regression analysis.
Results
1 The average levels of triglyceride, systolic blood pressure, insulin, leptin were significantly higher and the levels of high-density-lipoprotein-cholesterol, adiponectin were lower in the obese groups compared with the normal weight groups in boys(TG: 1.74±0.91mmol/l & 0.76±0.22mmol/l; SBP: 123.60±14.11mmHg& 111.38±10.18mmHg; INS: 28.72±13.79mIU/l, 16.74±6.53 mIU/l; LEP: 19.49±6.94μg/l & 8.08±4.15μg/l; HDL-C: 1.07±0.25mmol/l & 1.36±0.33mmol/l; ADIPO: 3.50±1.50mg/l & 5.28±2.68mg/l, all P<0.05). In the girls, the average levels of triglyceride, systolic blood pressure, diastolic blood pressure, insulin, leptin were higher and High-density-lipoprotein-cholesterol, adiponectin were lower compared with the normal group(TG: 1.43±0.64mmol/l & 0.91±0.25mmol/l; SBP: 115.48±10.47mmHg & 105.95±9.71 mmHg; DBP: 73.73±8.84 & 66.53±8.53; INS: 24.51±10.93 mIU/l & 17.12±5.45 mIU/l; LEP: 27.55±4.23μg/l & 17.93±5.08μg/l; HDL-C: 1.13±0.23mmol/l & 1.48±0.33mmol/l; ADIPO: 4.66±3.06mg/l & 6.33±3.64mg/l, all P<0.05). The prevalence of MS was 30.23% in the obese group which was higher compared with the normal group (P<0.05).
2 Serum leptin levels was lower in boys compared with that in girls(obese groups: 19.49±6.94μg/l & 27.55±4.23μg/l; normal groups: 8.08±4.15μg/l & 17.93±5.08μg/l, all P<0.01); and adiponectin levels was also lower in boys compared with that in girls than in girls(obese groups: 3.50±1.50 mg/l & 4.66±3.06 mg/l; normal groups: 5.28±2.68 mg/l & 6.33±3.64 mg/l, all P<0.05).
3 In simple linear correction analysis, leptin was positively correlated with BMI, waist circumference, serum insulin, triglyceride, systolic blood pressure in both boy and girl groups (BMI: r= 0.722 & r= 0.812; WC: r= 0.778 & r= 0.796; INS: r=0.625 & r=0.438; TG: r= 0.576 & r= 0.389; SBP: r=0.415 & r =0.359, all P<0.05), and only positively correlated with diastolic blood pressure in girls(r=0.395, P<0.05). And inversely correlated with high-density lipoprotein cholesterol (r=-0.347 & r=-0.535; P<0.01). But after controlling BMI, leptin merely correlated with serum insulin (partial r=0.402, P<0.05) in boys.
4 In simple linear correlation, adiponectin inversely correlated with BMI, waist circumference, fasting serum insulin, triglycerides in both boys and girls(BMI: r=-0.350 & r=-0.299; WC: r=-0.405 & r=-0.317; INS: r=-0.232 & r=-0.327; TG: r=-0.301 & r=-0.240, all P<0.05) and and positively correlated with high-density lipoprotein cholesteral in all subjects(male: r=0.251, female: r=0.260; P<0.05). But after controlling body mass index, adiponectin did not correlate with fasting serum insulin, triglycerides, high-density lipoprotein cholesteral(P>0.05).
5 BMI positively correlated with triglyceride, systolic blood pressure, diastolic blood pressure, insulin in both boys and girls(TG:r=0.664 & r=509; SBP: r=0.532 & r=0.562; DBP: r=0.24 & r=0.513; INS: r= 0.504 & r= 0.545, all P<0.05), and negatively correlated with high-density-lipoprotein-cholesterol in all subjects(male: r= -0.419, female: r=-0.599, P<0.05). After controlling leptin and adiponectin, BMI sfill correlated with the triglyceride, High-density-lipoprotein-cholesterol, systolic blood pressure, diastolic blood pressure in boys and girls(TG: partial r=0.407 & partial r=0.364; SBP: partial r=0.368 & partial r=0.509; DBP: partial r=0.218 & partial r=0.393; HDL-C: partial r=-0.259 & partial r=-0.337, all P<0.05). After controling leptin, BMI positively correlated with insulin in girls and did not correlat with insulin in boys(P>0.05).
6 The result of logistic regression showed BMI and insulin were the risk factors of MS in obese adolescents(BMI: OR=1.974; INS: OR=1.884, P<0.05).
Conclusions
1 There are lipids abnormality, increased blood pressure, increaced serum leptin and insulin level, decreaced adiponectin level in obese adolescents. And the prevalence of MS is higher in obese adolescents than normal weight adolescents.
2 Leptin correlates with triglyceride, systolic blood pressure, diastolic blood pressure, High-density-lipoprotein-cholesterol; and adiponectin correlates with triglyceride, High-density-lipoprotein-cholesterol. The increased serum leptin and decreased adiponectin may be related with the metabolic syndrome in obese adolescents.
3 Leptin correlates with serum insulin. Leptin may be one of the main causes of the increased serum insulin in male adolesents.
4 The degree of obesity and increased serum insulin level are risk factors of the MS.
脂肪组织不仅可以贮存能量,也可以分泌多种有生物活性的脂肪因子。瘦素(leptin,LEP)和脂联素(adiponectin,ADIPO)即是由脂肪细胞分泌的脂肪因子。ob/ob小鼠由于瘦素缺乏表现为肥胖,给予外源性瘦素后,进食减少,能量消耗增加,体重逐渐降低;随后的研究发现大多数肥胖者血液中瘦素含量与正常体重者相比是升高的,但并没有出现体重下降。研究显示瘦素可作用于脂肪、肌肉、肝脏、血管等外周组织,参与脂质代谢、血压调节,可能和代谢综合征的发生有关。脂联素是由脂肪细胞分泌的脂肪因子,和同样是脂肪因子的瘦素不同,脂联素在肥胖者血液中相对于体重正常者是降低的。目前研究显示其参与糖、脂代谢的调节,增加胰岛素的敏感性,可能和代谢综合征的发生有关。
瘦素、脂联素是否为代谢综合征的病因目前还不清楚。在瘦素、脂联素与代谢综合征组分的相关性研究中结论很不一致。青春期是儿童期肥胖发生率较高的时期,青春期肥胖亦易延续为成年肥胖,且儿童较成年人少并发糖尿病、心血管疾病,更易把瘦素、脂联素与代谢综合征组分的相关性表现出来。本研究以青春期儿童为研究对象,探讨瘦素、脂联素与代谢综合征的关系,为代谢综合征的发病机制研究和早期防治提供理论依据。
目的
1了解在肥胖儿童体内血糖、血脂、血压、瘦素、脂联素水平变化。
2探讨瘦素、脂联素与代谢综合征的关系。
对象与方法
共选取13～15岁青春期儿童177名,肥胖86人,男45人,女41人;体重正常者91人,男51人,女40人。测量身高(height)、体重(weight)、腰围(waistcircumference,WC)、臀围(hip circumference)、收缩压(systolic blood pressure,SBP)和舒张压(diastolic blood pressure,DBP),计算身体质量指数(body mass index,BMI)和腰臀比(waist-to-hip ratio,WHR)。抽取晨起空腹静脉血,测定血糖(glucose,GLU)、血甘油三酯(triglyceride,TG)和高密度脂蛋白胆固醇(High-density-lipoprotein-cholesterol,HDL-C),用放射免疫分析法(radioimmunoassay,RIA)测定血清胰岛素(insulin,INS)和瘦素,用酶联免疫吸附试验(enzymelinked immunosorbent assay,ELISA)测定血清脂联素。代谢综合征的诊断采用修正的美国学者Cook提出青少年人群MS诊断标准。数值变量均数比较用t检验和单因素方差分析,两变量相关分析用pearson相关和偏相关分析,分类变量进行χ~2检验,用logistic回归进行肥胖儿童代谢综合征危险因素分析。
结果
1男肥胖组甘油三酯、收缩压、胰岛素、瘦素平均水平高于正常体重组,高密度脂蛋白胆固醇、脂联素平均水平低于正常体重组(TG:1.74±0.91mmol/l和0.76±0.22mmol/l:SBP:123.60±14.11mmHg和111.38±10.18 mmHg;INS:28.72±13.79mIU/l和16.74±6.53 mIU/l;LEP:19.49±6.94μg/l和8.08±4.15μg/l;HDL-C:1.07±0.25mmol/l和1.36±0.33mmol/l;ADIPO:3.50±1.50mg/l和5.28±2.68mg/l,P均＜0.05)。女肥胖组甘油三酯、收缩压、舒张压、胰岛素、瘦素水平高于体重正常组,高密度脂蛋白胆固醇、脂联素水平低于体重正常组(TG:1.43±0.64mmol/l和0.91±0.25mmol/l;SBP:115.48±10.47mmHg和105.95±9.71mmHg;DBP:73.73±8.84和66.53±8.53;INS:24.51±10.93 mIU/l和17.12±5.45mIU/l;LEP:27.55±4.23μg/l和17.93±5.08μg/l:HDL-C:1.13±0.23mmol/l和1.48±0.33mmol/l;ADIPO:4.66±3.06mg/l和6.33±3.64mg/l,P均＜0.05)。肥胖儿童代谢综合征检出率30.23%,高于体重正常儿童(P＜0.01)。
2血清瘦素水平肥胖组和体重正常组男性均低于女性(肥胖组:19.49±6.9μg/l和27.55±4.23μg/l,对照组:8.08±4.15μg/l和17.93±5.08μg/l,P均＜0.01);血清脂联素水平肥胖组和体重正常组男性也均低于女性(肥胖组:3.50±1.50 mg/l和4.66±3.06 mg/l,对照组:5.28±2.68 mg/l和6.33±3.64 mg/l,P均＜0.05)。
3瘦素与BMI、腰围、胰岛素、甘油三酯、收缩压呈正相关(BMI:男r=0.722,女r=0.812;WC:男r=0.778,女r=0.796;INS:男r=0.625,女r=0.438;TG:男r=0.576,女r=0.389;SBP:男r=0.415,女r=0.359,P均＜0.05),瘦素和女性舒张压呈正相关(r=0.395,P＜0.05),瘦素与高密度脂蛋白胆固醇均呈负相关(男r=-0.347和女r=-0.535,P＜0.05);控制BMI后,瘦素仅和男性胰岛素有正相关(偏相关系数=0.402,P＜0.05),与男女甘油三酯、高密度脂蛋白胆固醇、收缩压、舒张压均无相关性(P＞0.05)。
4脂联素与BMI、腰围、胰岛素、甘油三酯呈负相关(BMI:男r=-0.350,女r=-0.299;WC:男r=-0.405,女r=-0.317;INS:男r=-0.232,女r=-0.327;TG:男r=-0.301,女r=-0.240,P＜0.05),与高密度脂蛋白胆固醇呈正相关(男r=0.251,女r=0.260,P＜0.05);控BMI后,脂联素与甘油三酯、高密度脂蛋白胆固醇、胰岛素均无相关性(P＞0.05)。
5 BMI与甘油三酯、收缩压、舒张压、胰岛素呈正相关(TG:男r=0.664,女r=509;SBP:男r=0.532,女r=0.562;DBP:男r=0.24,女r=0.513;INS:男r=0.504,女r=0.545,P＜0.05),和高密度脂蛋白胆固醇呈负相关(男r=-0.419,女r=-0.599,P＜0.05);控制瘦素、脂联素进行偏相关分析,BMI与甘油三酯、收缩压、舒张压、高密度脂蛋白胆固醇仍有相关(TG:男偏相关系数=0.407,女偏相关系数=0.364;SBP:男偏相关系数=0.368,女偏相关系数=0.509;DBP:男偏相关系数=0.218,女偏相关系数=0.393:HDL-C:男偏相关系数=-0.259,女偏相关系数=-0.337,P均＜0.05)。控制瘦素后进行偏相关分析,女BMI与胰岛素有相关性(偏相关系数=0.435,P＜0.05),男BMI与胰岛素无相关性(P＞0.05)。
6肥胖儿童代谢综合征危险因素logistic回归分析显示,BMI、胰岛素是肥胖儿童发生代谢综合征的危险因素(BMI:OR=1.974;INS:OR=1.884,P＜0.05)。
结论
1青春期肥胖儿童中存在脂代谢异常,血压升高,血清瘦素、胰岛素水平增高和脂联素水平降低,肥胖儿童代谢综合征检出率增高。
2青春期儿童血清瘦素与甘油三酯、收缩压、舒张压呈正相关,与高密度脂蛋白胆固醇呈负相关;脂联素与甘油三酯呈负相关,高密度脂蛋白胆固醇呈正相关;对于肥胖儿童,血清瘦素升高、脂联素降低可能和其代谢综合征发生率较高有关。
3血清瘦素与胰岛素水平呈正相关;瘦素可能是引起青春期男性儿童血清胰岛素升高的主要因素之一。
4肥胖程度、空腹血清胰岛素水平是肥胖儿童发生代谢综合征的危险因素。
Obesity is a kind of nutritional imbalance disease caused by intaking more energy than consumption under the genetic and environmental factors, and has become a worldwide epidemic. Obesity can result in all kinds of chronic diseases such as diabetes mellitus and cardiovascular disease. Metabolic Syndrome(MS) is a new concept developmented recently. It refers to a series of metabolic disorders in identical individual, including dyslipidemia, abdominal obesity, elevated blood pressure, and impaired glucose tolerance. And MS is a risk factor of cardiovascular disease and type 2 diabetes. The existing epidemiological investigations showed the prevalence of MS is higher in obese population than that of the normal weignt population. Obesity can contribute to the incidence of metabolic syndrome obviously although its underlying pathophysiology is unclear.
Adipose tissue can not only store energy, but also secrete a variety of bioactive substances. Leptin(LEP) and adiponectin(ADIPO) are two adipokines secreted by adipocytes. The main physiological function of leptin can act on the hypothalamus and reduce food intake and increase energy expenditure, at last result in weight loss. The level of leptin is higher in obese bosy compared with the normal. Recent studies show that leptin may also act in peripheral tissues, such as adipose tissue, muscle, liver, and so on. And it is involved in blood pressure regulation and lipid metabolism. So leptin may be a risk factor of MS. Adiponecein is another adipose tissue-specific adipokine. However plasma Adiponecein level is lower in obese individual than that of normal . Adiponecein has many biofunctions, including the regulation of blood glucose and lipids, adiponecein can alao improve the sensitivity of insulin. So low adiponecein level may be a risk factor of MS.
To date, the relatipnship of leptin, adiponectin and MS is unclear. The incidence of obesity and MS is higher and obesity-related complications are less in adolescents than that in adults. The study was designed to explore the relationship between leptin, adiponecein and MS in adolescents to provide a therotical basis for further research.
Objectives
1 To understand the changes of blood pressure and plasma level of lipids, blood glucose, leptin and adiponecein.
2 To explore the relationship of serum leptin, adiponecein and MS.
Subjects and Methods
We enrolled 86 obese(male: 45, female: 41)and 91 weight normal (boy: 51, girl: 40) adolescents aged 13～15years. Height, weight, waist circumference(WC), hip circumference, systolic blood pressure (SBP) and diastolic blood pressure(DBP)were measured, body mass index(BMI) and waist-hip ratio(WHR) were calculated. Morning fasting venous blood samples were collected and blood glucose(GLU), blood triglyceride(TG), high-density-lipoprotein-cholesterol(HDL-C) were measured. Serum insulin and leptin were measured by radioimmunoassay(RIA), and serum adiponectin were measured by enzymelinked immunosorbent assay(ELISA). MS was defined according to the modified Cook's definition. Numerical variables were compared using one-sample T test and one-way ANOVA, Correlation of variables was evaluated using Pearson's correlation coefficient and partial correlation coefficient. Classification variables were tested using X~2 test and logistic regression analysis.
Results
1 The average levels of triglyceride, systolic blood pressure, insulin, leptin were significantly higher and the levels of high-density-lipoprotein-cholesterol, adiponectin were lower in the obese groups compared with the normal weight groups in boys(TG: 1.74±0.91mmol/l & 0.76±0.22mmol/l; SBP: 123.60±14.11mmHg& 111.38±10.18mmHg; INS: 28.72±13.79mIU/l, 16.74±6.53 mIU/l; LEP: 19.49±6.94μg/l & 8.08±4.15μg/l; HDL-C: 1.07±0.25mmol/l & 1.36±0.33mmol/l; ADIPO: 3.50±1.50mg/l & 5.28±2.68mg/l, all P<0.05). In the girls, the average levels of triglyceride, systolic blood pressure, diastolic blood pressure, insulin, leptin were higher and High-density-lipoprotein-cholesterol, adiponectin were lower compared with the normal group(TG: 1.43±0.64mmol/l & 0.91±0.25mmol/l; SBP: 115.48±10.47mmHg & 105.95±9.71 mmHg; DBP: 73.73±8.84 & 66.53±8.53; INS: 24.51±10.93 mIU/l & 17.12±5.45 mIU/l; LEP: 27.55±4.23μg/l & 17.93±5.08μg/l; HDL-C: 1.13±0.23mmol/l & 1.48±0.33mmol/l; ADIPO: 4.66±3.06mg/l & 6.33±3.64mg/l, all P<0.05). The prevalence of MS was 30.23% in the obese group which was higher compared with the normal group (P<0.05).
2 Serum leptin levels was lower in boys compared with that in girls(obese groups: 19.49±6.94μg/l & 27.55±4.23μg/l; normal groups: 8.08±4.15μg/l & 17.93±5.08μg/l, all P<0.01); and adiponectin levels was also lower in boys compared with that in girls than in girls(obese groups: 3.50±1.50 mg/l & 4.66±3.06 mg/l; normal groups: 5.28±2.68 mg/l & 6.33±3.64 mg/l, all P<0.05).
3 In simple linear correction analysis, leptin was positively correlated with BMI, waist circumference, serum insulin, triglyceride, systolic blood pressure in both boy and girl groups (BMI: r= 0.722 & r= 0.812; WC: r= 0.778 & r= 0.796; INS: r=0.625 & r=0.438; TG: r= 0.576 & r= 0.389; SBP: r=0.415 & r =0.359, all P<0.05), and only positively correlated with diastolic blood pressure in girls(r=0.395, P<0.05). And inversely correlated with high-density lipoprotein cholesterol (r=-0.347 & r=-0.535; P<0.01). But after controlling BMI, leptin merely correlated with serum insulin (partial r=0.402, P<0.05) in boys.
4 In simple linear correlation, adiponectin inversely correlated with BMI, waist circumference, fasting serum insulin, triglycerides in both boys and girls(BMI: r=-0.350 & r=-0.299; WC: r=-0.405 & r=-0.317; INS: r=-0.232 & r=-0.327; TG: r=-0.301 & r=-0.240, all P<0.05) and and positively correlated with high-density lipoprotein cholesteral in all subjects(male: r=0.251, female: r=0.260; P<0.05). But after controlling body mass index, adiponectin did not correlate with fasting serum insulin, triglycerides, high-density lipoprotein cholesteral(P>0.05).
5 BMI positively correlated with triglyceride, systolic blood pressure, diastolic blood pressure, insulin in both boys and girls(TG:r=0.664 & r=509; SBP: r=0.532 & r=0.562; DBP: r=0.24 & r=0.513; INS: r= 0.504 & r= 0.545, all P<0.05), and negatively correlated with high-density-lipoprotein-cholesterol in all subjects(male: r= -0.419, female: r=-0.599, P<0.05). After controlling leptin and adiponectin, BMI sfill correlated with the triglyceride, High-density-lipoprotein-cholesterol, systolic blood pressure, diastolic blood pressure in boys and girls(TG: partial r=0.407 & partial r=0.364; SBP: partial r=0.368 & partial r=0.509; DBP: partial r=0.218 & partial r=0.393; HDL-C: partial r=-0.259 & partial r=-0.337, all P<0.05). After controling leptin, BMI positively correlated with insulin in girls and did not correlat with insulin in boys(P>0.05).
6 The result of logistic regression showed BMI and insulin were the risk factors of MS in obese adolescents(BMI: OR=1.974; INS: OR=1.884, P<0.05).
Conclusions
1 There are lipids abnormality, increased blood pressure, increaced serum leptin and insulin level, decreaced adiponectin level in obese adolescents. And the prevalence of MS is higher in obese adolescents than normal weight adolescents.
2 Leptin correlates with triglyceride, systolic blood pressure, diastolic blood pressure, High-density-lipoprotein-cholesterol; and adiponectin correlates with triglyceride, High-density-lipoprotein-cholesterol. The increased serum leptin and decreased adiponectin may be related with the metabolic syndrome in obese adolescents.
3 Leptin correlates with serum insulin. Leptin may be one of the main causes of the increased serum insulin in male adolesents.
4 The degree of obesity and increased serum insulin level are risk factors of the MS.
引文
[1]Ogden CL,Carroll MD,Curtin LR,et al.Prevalence of overweight and obesity in the United States,1999-2004[J].JAMA,2006,295:1549-55.
[2]米杰,程红.儿童肥胖和代谢综合征[J].中国医刊,2007,42(5):17-20.
[3]米杰,程红,侯冬青,等.北京市2004年2-18岁儿童青少年超重和肥胖流行现状[J].中华流行病学杂志,2006,27(6):469-474.
[4]Ford ES,Giles WH,Dietz WH.Prevalence of the metabolic syndrome among US adults:findings from the third National Health and Nutrition Examination Survey[J].JAMA,2002,28:356-359.
[5]Cook S,Weitzman M,Auinger P,et al.Prevalence of a Metabolic Syndrome Phenotype in Adolescents[J].Arch pediatr Adolesc Med,2003,157:821-827.
[6]Cruz M,Weigensbeg M,Huang T,et al.the metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity[J].Clin Endocrinol Metab,2004,89(1):108-113.
[7]Kershaw EE,Flier JS.adipose tissue as an endocrine organ[J].Clin EndocrinolMetab,2004,80:2548-2556.
[8]陈名道.脂肪细胞产物与肥胖和代谢综合征[J].中华内分泌代谢杂志,2003,19:161-163.
[9]Pelleymounter MA,Cullen MJ,Baker MB,et al.Effects of the obese gene product on body weight regulation in ob/ob mice[J].Science,1995,269:540-543.
[10]龚大为,李平,朱大龙.脂肪因子研究进展[J].中国糖尿病杂志,2007,15(10):637-638.
[11]Galletti F,Barbato A,Versiero M,et al.circulating leptin levels predict the development of metabolic syndrone in middle-aged men:An 8-year follow-up stusy[J].J Hypertens,2007,25(8):1671-1677.
[12]李卉,姜一农.代谢综合征患者的血清瘦素[J].高血压杂志,2006,14(1):28-32.
[13]Berg AH,Combs TP,Du X,et al.The adipocyte secreted protein Acrp30enhances hepatic insulin action[J].Nature Medicine,2001,8:947-953.
[14]Yamauchi T,Kamon J,Minokoshi Y,et al.adiponectin stimulates glucose utilization and fatty acid oxidation by activating AMP-activated protein kinase[J]. Nature Medicine,2002,11:1288-1295.
[15]Ouchi N,Walsh K.adiponectin as an anti-inflammatory factor[J].Clin Chim Acta,2007,380:24-30.
[16]Berg AH,Scherer PE.adipose tissue,inflammation,and cardiovascular disease[J].Circ Res,2005,96:939-949.
[17]徐贵发,朱凤,刘春晓,等.城市居民血清瘦素水平与体质指数、血脂和胰岛素关系的研究[J].卫生研究,2005,34(2):205-207.
[18]Anahita H,Hossein F,ALireza M,et al.Metabolic syndrome and leptin concentrations in obese children[J].Indian J pediatr,2006,73(3):593-596.
[19]Sung SH,Chuang SY,Sheu WHH,et al.Adiponectin,but Not Leptin or High-Sensitivity C-Reactive Protein,Is Associated with Blood Pressure Independently of General and Abdominal Adiposity[J].Hypertens Res,2008,31:633-640.
[20]季成叶.中国学生超重肥胖BMI筛查标准的应用[J].中国学校卫生,2004,25(1):125-128.
[21]中华人民共和国教育部等编.2005年中国学生体质与健康调研报告[M].北京:高等教育出版社,2007,8:18-23.
[22]韩志钧等主编.临床化学常用项目自动分析法[M].沈阳:辽宁科学技术出版社,2005,8:977-980.
[23]中华人民共和国教育部等编.2005年中国学生体质与健康调研报告[M].高等教育出版社,2007,8:196-197.
[24]宋秀霞.国际糖尿病联盟代谢综合征全球共识定义[J].中华糖尿病杂志,2005,13:178-180.
[25]杨年红,周韫珍,毛丽梅,等.单纯性肥胖儿童血清瘦素水平与血糖及血脂变化的关系[J].中华预防医学院杂志,2003,37(3):186-188.
[26]罗勇,李小平,覃数,等.超重及肥胖患者血清抵抗素与脂联素水平[J].中华高血压杂志.2007,15(6):505-506.
[27]Koerner A,Kratzsch J,Kiess W.adipocytokines:leptin-the lassical,resistin-the controversial,ADIPOnectin-the promising,and more to come[J].Best Pract Res Clin Endocrinol Metab,2005,19:525-546.
[28] Zubin P, Edgard ED, Jennifer O, et al. adiponectin, adiposity, and Insulin Resistance in Children and Adolescents[J]. J Clin Endocrinol Metab, 2006, 91: 2119-2125.
[29] Korner A, Wabitsch M, Seidel B, et al. adiponectin xpression in humans is dependent on differentiation of adipocytes and down-regulated by humoral serum components of high molecular weight[J]. Biochem Biophys Res Commun, 2005, 337: 540-550.
[30] Yamauchi M, Moss KA, Bovenkerk JE, et al. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor[J]. Obes Res, 2005,13: 662-669.
[31] Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance [J]. Diabetologia, 2003,46: 1594-1603.
[32] Nilsson L, Binart N, Bohlooly Y ,et al. Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue[J]. Biochem Biophys Res Commun, 2005, 331: 1120-1126.
[33] Xu A, Chan KW, Hoo RL, et al. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes[J]. J Biol Chem, 2005, 280: 18073-18080
[34] Huang KC, Lue BH, Yen RF, et al. Plasma adiponectin levels and metabolic factors in nondiabetic adolescents[J]. Obes Res, 2004,12: 119-124.
[35] Cote M, Mauriege P, Bergeron J, et al. adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men[J]. J Clin Endocrinol Metab, 2005, 90: 1434-1439.
[36] Milan G, Granzotto M, Scarda A, et al. Resistin and adiponectin expression in visceral fatofobese rats: effectofweight loss[J]. ObesRes, 2002,10: 1095-1103.
[37] Lihn AS, Bruun JM, He G, et al. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects[J]. Mol Cell Endocrinol, 2004, 9:215-219.
[38] Demerath EW, Towne B, Wisemandle W, et al. Serum leptin concentration, body composition,and gonadal hormones during puberty [J]. Int J Obes Relat Metab Disord,1999,23:678-685.
[39]Casabiell X,Rinciro V,Peino R,et al.Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro:dexameshasone and estradiol stimulate leptin release in women,but not in men[J].J Clin Endcrinol Metab,1998,83:2149-2155.
[40]Wabitsch M,Blum WF,Muche R,et al.Contribution of and gene to gender difference in leptin production in obese children and adolescents[J].J Clin Invest,1997,100:808-813.
[41]王遂军,贾伟平,包玉倩,等.血清脂联素与肥胖的关系[J].中华内分泌代谢杂志,2005,21(1):36-38.
[42]Wajchenberg BL.Subcutaneous and visceral adipose tissue:their relation to the metabolic syndrome[J].Endocr Rev,2000,21:697-738.
[43]Nishizawa H,Shimomura I,Kishida K,et al.Androgens decrease plasma adiponectin,an insulin-sensitizing adipocytederived protein[J].Diabetes,2002,51:2734-2741.
[44]Tsou PL,Jiang YD,Chang CC,et al.Sex-related differences between adiponectin and insulin resistance in schoolchildren[J].Diabetes Care,2004,27:308-313.
[45]Lanfranco F,Zitzmann M,Simoni M et al.Serum adiponectin levels in hypogonadal men:influence of testosterone replacement therapy[J].Clinical Endocrinology,2004,60:500-507.
[46]Huang KC,Lin RCY,Kormas N,et al.Plasma leptin is associated with insulin resistance independent of age,body mass index,fat mass,lipids,and pubertal development in nondiabetic adolescents[J].International Journal of Obesity,2004,28:470-475.
[47]Valle M,Gascon F,Martos R,et al.Relationship between high plasma leptin concentrations and metabolic syndrome in obese prepubertal children[J].International Journal of Obesity,2003,27:13-18.
[48]胡静芳,吴国亭,秦利.老年代谢综合征患者血清瘦素水平与胰岛素抵抗的 研究[J].内科理论与实践,2008,3(5):335-338.
[49]Seufert J,Kieffer TJ,Leech CA,et al.Leptin suppression of insulin secretion and gene expression in human pancreatic islets:implications for the development of adipogenic diabetes mellitus[J].J Clin Endocrinol Metab,1999,84:670-676.
[50]D'Adamo M,Buongiorno A,Marcocia E,et al.Increased ob gene expression leads to elevated plasma leptin concentrations in patients with chronic primary hyperinsulinemia[J].Diabetes,1998,47:1625-1629.
[51]Cohen B,Novick D,Rubinstein M.Modulation of insulin activities by leptin[J].Science,1996,274:1185-1188.
[52]Collier GR,De Silva A,Sanigorski A,et al.Development of obesity and insulin resistance in the Israeli sand rat.Does leptin play a role[J].Ann NY Acad Sci,1997,827:50-63.
[53]Vikram NK,Misra A,Pandey RM,et al.adiponectin,insulin resistance,and C-reactive protein in postpubertal Asian Indian adolescents[J].Metabolism,2004,53:1336-1341.
[54]Kettaneh A,Heude B,Oppert JM,et al.Serum adiponectin is related to plasma high-density lipoprotein cholesterol but not to plasma insulin-concentration in healthy children:the FLVS Ⅱ study[J].Metabolism,2006,55:1171-1176.
[55]Weiss R,Dufour S,Groszmann A,et al.Low adiponectin levels in adolescent obesity:a marker of increased intramyocellular lipid accumulation[J].J Clin Endocrinol Metab,2003,88:2014-2018.
[56]MatsuzawaY,FunahashiT,Kihara S,et al.adiponectin andmetabolic syndrome[J].Arterioscler ThrombVasc Bio,2004,24(1):29-38.
[57]Yamauchi T,Kamon J,Minokoshi Y,et al.adiponectin stimulates glucose utilization and fatty-acid oxidation by activating ampactivated protein kinase[J].Nat Med,2002,8:1288-1295.
[58]Pajvani UB,Hawkins M,Combs TP,et al.Complex distribution,not absolute amount of adiponectin,correlates with thiazolidinedione mediated improvement in insulin sensitivity[J].J Biol Chem,2004,279:12152-12162.
[59]Xu A,Wang Y,Keshaw H,et al.The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice[J]. Journal of Clinical Investigation, 2003,112: 91-100.
[60] Wagner A, Simon c, Oujaa M, et al. adiponectin is associated with lipid profile and insulin sensitivity in French adolescents[J]. Diabetes & Metabolism, 2008, 34:465-471.
[61] Verges B, Petit JM, Duvillard L, et al. adiponectin is an important determinant of ApoA-I catabolism[J]. Arterioscler Thromb Vasc Biol, 2006,26: 1364-1369.
[62] Schneider JG, von Eynatten M, Schneider S, et al. Low plasma adiponectin levels are associated with increased hepatic lipase activity in vivo[J]. Diabetes Care, 2005,28: 2181-2186.
[63] Petersen KF, Oral EA, Dufour S, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy[J]. J Clin Invest, 2002, 109: 1345-1350.
[64] Simha V, Szczepaniak LS, Wagner AJ, et al. Effect of leptin replacement on intrahepatic and intramyocellular lipid content[J]. Metabolism, 2006, 55: 1171-1176.
[65] Steinberg GR, Parolin ML, Heigenhauser GJ, et al. Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance[J]. Am J Physiol Endocrinol Metab, 2002,283(1): E187-E192.
[66] Huang h, Dedousis N, Bandi A, et al. Liver Triglyceride Secretion and Lipid Oxidative Metabolism Are Rapidly Altered by Leptin in Vivo [J]. Endocrinology, 2006,147(3): 1480-1487.
[67] Sudi KM, Gallistl S, Weinhandl G, et al. No evidence for leptin as an independent associate of blood pressure in childhood and juvenile obesity[J]. J Pediatr Endocrinol Metab, 2000, 13: 513-521.
[68] Adamczak M, Wiecedil T, Funahashi T, et al. Decreased plasma adiponectin concentration in patients with essential hypertension[J]. Am J Hypertens, 2003, 16: 72-75.
[69] Agata J, Masuda A, Takada M, et al. High plasma immunoreactive leptin level in essential hypertension[J]. Am J Hypertens, 1997, 10: 1171-1174.
[70]Kokot F,Adamczak M,Wiecek A,et al.Does leptin play a role in the pathogenesis of essential hypertension?[J].Kidney Blood Press Res,1999,22:154-160.
[71]Suter PM,Locher R,Hasler E,et al.Is there a role for the ob gene product leptin in essential hypertension?[J].Am J Hypertens,1998,11:1305-1311.
[72]Almeida PB,Gimeno SG,Freire RD,et al.Leptin is not associated independently with hypertension in Japanese-Brazilian women[J].Braz J Med BiolRes,2006,39(1):99-105.
[73]Maryam G,Hossein F,Alireza M,et al.Serum Leptin Levels and Hypertension in Iranian Obese Children[J].The Endocrinologist,2007,17:258-261.
[74]Ohashi K,Kihara S,Ouchi N,et al.adiponectin replenishment ameliorates obesity-related hypertension[J].Hypertension,2006,47(6):1108-1116.
[75]张美仙,米杰,赵小元,等.瘦素和脂联素在儿童肥胖相关性高血压发病中的作用[J].中国循证儿科杂志,2008,13(2):96-102.
[76]Cesari M,Pessina AC,Zanchetta M,et al.Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high risk nondiabetic patients[J].J Intern Med,2006,260:474-483.
[77]Mallamaci F,Zoccali C,Cuzzola F,et al.adiponectin in essential hypertension[J].J Nephrol,2002,15:507-511.
[78]罗勇,李小平,覃数,等.超重及肥胖患者血清抵抗素与脂联素水平[J].中华高血压杂志.2007,15(6):505-506.
[79]Yang WS,Lee WJ,Funahashi T,et al.Plasma adiponectin levels in overweight and obese Asians[J].Obes Res,2002,10:1104-1110.
[80]Hrang KC,Chen CL,Chuang LM,et al.Plasma adiponectin Levels and Blood Pressures in Nondiabetic Adolescent Females[J].J Clin Endocrinol Metab,2003,88:4130-4134.
[81]Adamczak M,Wiecedil,Funahashi T,et al.Decreased plasma adiponectin concentration in patients with essential hypertension[J].Am J Hypertens,2003,16:72-75.
[82]徐轶群,季成叶,马军,等.女性青少年血清脂联素水平与血压的关系研究[J].中国学校卫生,2007,28(4):292-293.
[83]Ogawa Y,Masuzaki H,Hosoda K,et al.Increased glucose metabolism and insulin sensitivity in Transgenic SkinnyMice over expressing leptin[J].Diabetes,1999,48:1822-1829.
[84]Combs TP,Berg AH,Scherer PE,et al.Endogenous glucose production is inhibited by the adipose-derived protein Acrp30[J].J Clin Invest,2001,108:1875-1881.
[85]Wu X,Motoshima H,Mahadev K,et al.Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes[J].Diabetes,2003,52:1355-1363.
[86]Christoph H,Lorenz R,Guenter H,et al.Low serum adiponectin is indepen-dently associated with both the metabolic syndrome and angiographically determined coronary atherosclerosis[J].Clinica Chimica Acta,2007,383:97-102.
[87]Gilardini L,McTernan PG,Girola A,et al.adiponectin is a candidate marker of metabolic syndrome in obese children and adolescents[J].Atherosclerosis,2006,189:401-407.
[88]Gabriel QS,Martha LC,Mrc JW,et al.adiponectin Independently Predicts Metabolic Syndrome in Overweight Latino Youth[J].J Clin Endocrinol Metab,2007,92:1809-1813.
[89]Anahita H,Hossein F,Alireza M,et al.Metabolic Syndrome and Leptin Concentrations in Obese Children[J].Indian J Pediatr,2006,73(7):593-596.
[90]张建,华琦主编.代谢综合征[M].人民卫生出版社,2003,10:8-11.
[1]Ford ES,Giles WH,Dietz WH et al.Prevalence of the metabolic syndrome among US adults:findings from the third National Health and Nutrition Examination Survey[J].JAMA,2002,287:356-359.
[2]顾东风,Reynold K,杨文杰,等.中国成人代谢综合征的患病率[J].中华糖尿病杂志,2005,13(3):181-186.
[3]Cook S,Weitzman M,Auinger P,et al.Prevalence of a Metabolic Syndrome Phenotype in Adolescents[J].Arch pediatr Adolesc Med,2003;157:821-827.
[4]Cruz M,Weigensbeg M,Huang T,et al.The Metabolic Syndrome in Oveweight Hispanic Youth and the Role of Insulin Sensitivity.[J]Clin Endocrinol Metab,2004,89(1):108-113.
[5]米杰,程红.儿童肥胖和代谢综合征[J].中国医刊,2007,42(5):17-20.
[6]Ogden CL,Carroll MD,Curtin LR,et al.Prevalence of overweight and obesity in the United States,1999-2004[J].JAMA,2006,295:1549-1555.
[7]米杰,程红,侯冬青,等.北京市2004年2-18岁儿童青少年超重和肥胖流行现状[J].中华流行病学杂志,2006,27(6):469-474.
[8]Zhang Y,Proenca R,Maffei M,et al.Positional cloning of the mouse obese gene and its human homologue[J].Nature(Lond),1994,372:425-432.
[9]Muoio DM,Lynis DG.Peripheral metabolic actions of leptin[J].Best Pract Res Clin Endocrinol Metab,2002,16:653-666.
[10]柏晓璐,戴秋艳.瘦素与代谢综合征[J].内科理论也实践,2008,3(3):207-210.
[11]Gura T.leptin not impressive in clinical trial[J].Science,1999,286:881-882.
[12]Haj FG,Zabolotny JM,Kim YB,et al.Liver-specific proteintyrosine phosphatase 1B(PTP1B) re-expression alters glucose homeostasis of PTP1B-/-mice[J].J Biol Chem,2005,280:15038-15046.
[13]Scarpace PJ,Matheny M,Tumer N,et al.leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats[J].Diabetologia,2005,48:1075-1083.
[14] Shimomura I, Hammer RE, Ikemoto S, et al. leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy[J]. Nature, 1999, 401:73-76.
[15] Petersen KF, Oral EA, Dufour S, et al. leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy[J]. J Clin Invest, 2002, 109: 1345-1350.
[16] Ogawa Y, Masuzaki H, Hosoda K, et al. Increased glucose metabolism and insulin sensitivity in Transgenic Skinny Mice overexpressing leptin.Diabetes[J]. 1999,48:1822-1829.
[17] Steinberg GR, Bonen A, Dyck DJ. Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic leptin treatment in rats[J]. Am J Physiol, 2002, 282: E593-E600.
[18] Minokoshi Y, Kahn BB. Role of AMP-activated protein kinase in leptin induced fatty acid oxidation in muscle[J]. Biochem Soc Trans, 2003, 31: 196-201.
[19] Atkinson LL, Fischer MA, Lopaschuk GD. leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinaseacetyl- CoA carboxylase-malonyl-CoA axis[J]. J Biol Chem, 2002,277: 29424-29430.
[20] Huang W, Dedousis N, Bhatt BA, et al. Impaired activation of phosphatidylin- ositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in diet-induced obesity[J]. J Biol Chem, 2004,279: 21695-21700.
[21] Huang h, Dedousis N, Bandi A, et al. Liver Triglyceride Secretion and Lipid Oxidative Metabolism Are Rapidly Altered by leptin in Vivo [J]. Endocrinology, 2006,147(3): 1480-487.
[22] Steinberg GR, Parolin ML, Heigenhauser GJ, et al. leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance[J]. Am J Physiol Endocrinol Metab, 2002,283(1): E187-E192.
[23] Carlyle M, Jones OB, Kuo JJ, et al. Chronic Cardiovascular and Renal Actions of leptin: Role of Adrenergic Activity[J]. Hypertension, 2002, 39: 496-501.
[24] Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome[J]. Hypertens Res, 2006,29: 839-847.
[25] Correia ML, Haynes WG, Rahmouni K, et al. The concept of selective leptin resistance: evidence from agouti yellow obese mice[J]. Diabetes, 2002, 51(2): 439-442.
[26] Rahmouni K, Morgan DA, Morgan GM, et al. Role of selective leptin resistance in diet-induced obesity hypertension[J]. Diabetes, 2005, 54:2012-2018.
[27] Lembo G, Vecchione C, Fratta L, et al. leptin induces direct vasodilation through distinct endothelial mechanisms[J]. Diabetes, 2000,49(2): 293-297.
[28] Fruhbeck G. Pivotal role of nitric oxide in the ocntrol of Blood Pressure after leptin administration[J]. Diabetes, 1999,48: 903-908.
[29] Mackintosh RM, Hirsch J. The effects of leptin administration in nonobese human subjects[J]. Obes Res, 2001 ,9:462-469.
[30] Agata J, Masuda A, Takada M, et al. High plasma immunoreactive leptin level in essential hypertension[J]. Am J Hypertens, 1997,10: 1171-1174.
[31] Serum leptin Levels and Hypertension in Iranian Obese Children[J]. The Endocrinologist, 2007,17: 258-261.
[32] Lee MJ, Fried SK. Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue[J]. J Lipid Res, 2006,47(9): 1984-1993.
[33] Muzumdar R, Ma X, Yang X, et al. Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms[J]. FASEB J, 2003, 17:1 130-1132.
[34] D'Adamo M, Buongiorno A, Marcocia E, et al. Increased ob gene expression eads to elevated plasma leptin concentrations in patients with chronic primary hyperinsulinemia [J]. Diabetes, 1998,47:1625-1629.
[35] Coralia P, Carmen FG, Teresa FA, et al. leptin impairs insulin signaling in rat adipocytes[J]. Diabetes, 2004, 53(2): 347-353.
[36] Zhao YF, Chen C. Regulation of pancreatic β-cell function by adipocytes [J]. Sheng Li Xue Bao, 2007, 59(3): 247- 252.
[37] Bodary PF, Westrick RJ, Wickenheiser KJ, et al. Effect of leptin on Arterial Thrombosis Following Vascular Injury in Mice[J]. JAMA, 2002, 287: 1706-1709.
[38]Barouch LA,Berkowitz DE,Harrison RW,et al.Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice[J].Circulation,2003,108(6):754-759.
[39]庄向华,董砚虎,许爱梅,等.糖尿病一级亲属脂联素和瘦素与胰岛素抵抗的相关性[J].中华糖尿病杂志,2005,13(1):8-10.
[40]Circulating leptin levels predict the development of metabolic syndrome in middle-aged men:an 8-year follow-up study[J].J Hypertens,25:1671-1677.
[41]Yamauchi T,Kamon J,Ito Y,et al.Cloning of adiponectin receptors that mediate antidiabetic metabolic effects[J].Nature,2003,423:762-769.
[42]Halleux CM,Takahashi M,Delporte ML.Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue[J].Biochem Biophys Res Commun,2001,16(288):1102-1107..
[43]Nishizawa H,Shimomura I,Kishida K,et al.Androgens decrease plasma ADIPOnectin,an insulin-sensitizing adipocytederived protein[J].Diabetes,2002,51:2734-2741.
[44]Yu JG,Javorchi S,Hevener AL,et al.The effect of thiazolidinediones on plasma adiponectin levels in normal,obese,and type 2 diabetic subjects[J].Diabetes,2002,51(8):2968-2974.
[45]唐金凤,杨颖,汪启迪,等.血清脂联索水平与肥胖度的关系[J].中华内分泌代谢杂志,2003,19(2):166-168.
[46]Yatagai T,Nagasaka S,Taninguchi A,et al.Hypoadiponectinemia is associated with visceral fat accumulation an insulin resistance in Japanese marl with type 2diabetes mellitus[J].Metabolism,2003,52(8):1274-1278.
[47]Berg AH,Combs TP,Du X,et al.The adipocytesecreted protein Acrp30enhances hepatic insulin action[J].Nat Med,2001,7:947-953.
[48]Nawrocki AR,Rajala MW,Tomas E,et al.Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferatoractivated receptor gamma agonists[J].J Biol Chem,2006,281:2654-2660.
[49]Tomas E,Tsao TS,Saha AK,et al.Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation[J]. Proc Natl Acad Sci U S A, 2002, 99: 16309-16313.
[50] Berg AH, Combs TP, Du X, et al. The adipocyte secreted protein Acrp30 enhances hepatic insulin action[J]. Nat Med, 2001,7: 947-953.
[51] Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J]. Nat Med, 2001,7: 941-946.
[52] Xu A, Wang Y, Keshaw H, et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice[J]. Journal of Clinical Investigation, 2003,112: 91-100.
[53] Stefan N, Stumvoll M, Vozarova B, et al. Plasma adiponectin and endogenous glucose production in humans[J]. Diabetes Care, 2003, 26: 3315-3319.
[54] Miyazaki Y, Mahankali A, Wajcberg E, et al. Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients[J]. J Clin Endocrinol Metab, 2004, 89: 4312-4319.
[55] Bugianesi E, Pagotto U, Manini R, et al. Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity[J]. J Clin Endocrinol Metab, 2005, 90: 3498-3504.
[56] Yamauchi T, Kamon J, Minokoshi Y, et al. adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase[J]. Nat Med, 2002, 8: 1288-1295.
[57] Yamauchi T, Kamon J, Minokoshi Y, et al. adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase[J]. Nat. Med, 2002, 8: 1288-1295.
[58] Matsuzawa Y, Funahashi T, Kihara S, et al. adiponectin and metabolic syndrome[J]. Arterioscler ThrombVasc Biol, 2004, 24(1): 29-38.
[59] Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesusmonkeys[J]. Diabetes,2001,50.(5):1126-1133.
[60]Yamauchi T,Kamon J,Waki H,et al.The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J].Nat.Med,2001,7:941-946.
[61]Goldstein BJ,Scalia R.adiponectin:a novel adipokine linking adipocytes and vascular function[J].J Clin Endocrinol Metab,2004,89(6):2563-2568.
[62]Ohashi K,Kihara S,Ouchi N,et al.adiponectin replenishmentameliorates obesity-related hypertension[J].Hypertension,2006,47(6):1108-1116.
[63]徐轶群,季成叶,马军,等.女性青少年血清脂联素水平与血压的关系研究[J].中国学校卫生,2007,28(4):292-293.
[64]Ouchi N,Walsh K.adiponectin as an anti-inflammatory factor[J].Clin Chim Acta,2007,380:24-30.
[65]Ouchi N,Kihara S,Arita Y,et a.l adipocyte-derived plasma protein,adiponectin,suppresses lipid accumulation and classA scavenger receptor expression in humanmonocyte-derived macrophages[J].Circulation,2001,103(8):1057-1063.
[66]Kumada M,Kihara S,Ouchi N,et al.adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages[J].Circulation,2004,109:2046-2049.
[67]Matsuda M,Shimomura I,Sata M,et al.Role of adiponectin in preventing vascular stenosis-The missing link of adipo-vaseular axis[J].J BiolChem,2002,277(40):37487-37491.
[68]Okamoto Y,Kihara S,Ouchi N,et al.ADIPOnectin reduces atherosclerosis in apolipoprotein E-deficient mice[J].Circulation,2002,106:2767-2770.
[69]Yamauchi T,Kamon J,Waki H,Imai Y,et al.Globular adiponectin protected ob/ob mice from diabetes and apoE deficient mice from atherosclerosis[J].J Biol Chem,2002,278:2461-2468.
[70]Shimabukuro M,Higa N,Asahi T,et al.Hypoadiponectinemia is closely linked to endothelial dysfunction in man[J].J Clin Endocrinol Metab,2003,88:3236-3240.
[71]Tan KCB,Xy A,ChowWS,et al.Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation[J].J Clin Endocrinol Metab,2004,89:765-769.
[72]Pilz S,Horejsi R,Miler R,et al.Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin[J].J Clin EndocrinolMetab,2005,90(8):4792-4796.
[73]Lihn AS,Ostergard T,Nyholm B,et al.ADIPOnectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients[J].Am J Physiol Endocrinol Metab,2003,284:E443-E448.
[74]Daimon M,Oizumi T,Saitoh T,et al.Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese population-The Funagata study[J].Diabetes Care,2003,26(7):2015-2020.
[75]Haluzik M,Pafizkova J,Haluzik M,et al.adiponectin and its role in the obesity-induced insulin resistance and related complications[J].PhysiolRes,2004,53(2):123-129.
[2]米杰,程红.儿童肥胖和代谢综合征[J].中国医刊,2007,42(5):17-20.
[3]米杰,程红,侯冬青,等.北京市2004年2-18岁儿童青少年超重和肥胖流行现状[J].中华流行病学杂志,2006,27(6):469-474.
[4]Ford ES,Giles WH,Dietz WH.Prevalence of the metabolic syndrome among US adults:findings from the third National Health and Nutrition Examination Survey[J].JAMA,2002,28:356-359.
[5]Cook S,Weitzman M,Auinger P,et al.Prevalence of a Metabolic Syndrome Phenotype in Adolescents[J].Arch pediatr Adolesc Med,2003,157:821-827.
[6]Cruz M,Weigensbeg M,Huang T,et al.the metabolic syndrome in overweight Hispanic youth and the role of insulin sensitivity[J].Clin Endocrinol Metab,2004,89(1):108-113.
[7]Kershaw EE,Flier JS.adipose tissue as an endocrine organ[J].Clin EndocrinolMetab,2004,80:2548-2556.
[8]陈名道.脂肪细胞产物与肥胖和代谢综合征[J].中华内分泌代谢杂志,2003,19:161-163.
[9]Pelleymounter MA,Cullen MJ,Baker MB,et al.Effects of the obese gene product on body weight regulation in ob/ob mice[J].Science,1995,269:540-543.
[10]龚大为,李平,朱大龙.脂肪因子研究进展[J].中国糖尿病杂志,2007,15(10):637-638.
[11]Galletti F,Barbato A,Versiero M,et al.circulating leptin levels predict the development of metabolic syndrone in middle-aged men:An 8-year follow-up stusy[J].J Hypertens,2007,25(8):1671-1677.
[12]李卉,姜一农.代谢综合征患者的血清瘦素[J].高血压杂志,2006,14(1):28-32.
[13]Berg AH,Combs TP,Du X,et al.The adipocyte secreted protein Acrp30enhances hepatic insulin action[J].Nature Medicine,2001,8:947-953.
[14]Yamauchi T,Kamon J,Minokoshi Y,et al.adiponectin stimulates glucose utilization and fatty acid oxidation by activating AMP-activated protein kinase[J]. Nature Medicine,2002,11:1288-1295.
[15]Ouchi N,Walsh K.adiponectin as an anti-inflammatory factor[J].Clin Chim Acta,2007,380:24-30.
[16]Berg AH,Scherer PE.adipose tissue,inflammation,and cardiovascular disease[J].Circ Res,2005,96:939-949.
[17]徐贵发,朱凤,刘春晓,等.城市居民血清瘦素水平与体质指数、血脂和胰岛素关系的研究[J].卫生研究,2005,34(2):205-207.
[18]Anahita H,Hossein F,ALireza M,et al.Metabolic syndrome and leptin concentrations in obese children[J].Indian J pediatr,2006,73(3):593-596.
[19]Sung SH,Chuang SY,Sheu WHH,et al.Adiponectin,but Not Leptin or High-Sensitivity C-Reactive Protein,Is Associated with Blood Pressure Independently of General and Abdominal Adiposity[J].Hypertens Res,2008,31:633-640.
[20]季成叶.中国学生超重肥胖BMI筛查标准的应用[J].中国学校卫生,2004,25(1):125-128.
[21]中华人民共和国教育部等编.2005年中国学生体质与健康调研报告[M].北京:高等教育出版社,2007,8:18-23.
[22]韩志钧等主编.临床化学常用项目自动分析法[M].沈阳:辽宁科学技术出版社,2005,8:977-980.
[23]中华人民共和国教育部等编.2005年中国学生体质与健康调研报告[M].高等教育出版社,2007,8:196-197.
[24]宋秀霞.国际糖尿病联盟代谢综合征全球共识定义[J].中华糖尿病杂志,2005,13:178-180.
[25]杨年红,周韫珍,毛丽梅,等.单纯性肥胖儿童血清瘦素水平与血糖及血脂变化的关系[J].中华预防医学院杂志,2003,37(3):186-188.
[26]罗勇,李小平,覃数,等.超重及肥胖患者血清抵抗素与脂联素水平[J].中华高血压杂志.2007,15(6):505-506.
[27]Koerner A,Kratzsch J,Kiess W.adipocytokines:leptin-the lassical,resistin-the controversial,ADIPOnectin-the promising,and more to come[J].Best Pract Res Clin Endocrinol Metab,2005,19:525-546.
[28] Zubin P, Edgard ED, Jennifer O, et al. adiponectin, adiposity, and Insulin Resistance in Children and Adolescents[J]. J Clin Endocrinol Metab, 2006, 91: 2119-2125.
[29] Korner A, Wabitsch M, Seidel B, et al. adiponectin xpression in humans is dependent on differentiation of adipocytes and down-regulated by humoral serum components of high molecular weight[J]. Biochem Biophys Res Commun, 2005, 337: 540-550.
[30] Yamauchi M, Moss KA, Bovenkerk JE, et al. Regulation of adiponectin expression in human adipocytes: effects of adiposity, glucocorticoids, and tumor necrosis factor[J]. Obes Res, 2005,13: 662-669.
[31] Fasshauer M, Paschke R. Regulation of adipocytokines and insulin resistance [J]. Diabetologia, 2003,46: 1594-1603.
[32] Nilsson L, Binart N, Bohlooly Y ,et al. Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue[J]. Biochem Biophys Res Commun, 2005, 331: 1120-1126.
[33] Xu A, Chan KW, Hoo RL, et al. Testosterone selectively reduces the high molecular weight form of adiponectin by inhibiting its secretion from adipocytes[J]. J Biol Chem, 2005, 280: 18073-18080
[34] Huang KC, Lue BH, Yen RF, et al. Plasma adiponectin levels and metabolic factors in nondiabetic adolescents[J]. Obes Res, 2004,12: 119-124.
[35] Cote M, Mauriege P, Bergeron J, et al. adiponectinemia in visceral obesity: impact on glucose tolerance and plasma lipoprotein and lipid levels in men[J]. J Clin Endocrinol Metab, 2005, 90: 1434-1439.
[36] Milan G, Granzotto M, Scarda A, et al. Resistin and adiponectin expression in visceral fatofobese rats: effectofweight loss[J]. ObesRes, 2002,10: 1095-1103.
[37] Lihn AS, Bruun JM, He G, et al. Lower expression of adiponectin mRNA in visceral adipose tissue in lean and obese subjects[J]. Mol Cell Endocrinol, 2004, 9:215-219.
[38] Demerath EW, Towne B, Wisemandle W, et al. Serum leptin concentration, body composition,and gonadal hormones during puberty [J]. Int J Obes Relat Metab Disord,1999,23:678-685.
[39]Casabiell X,Rinciro V,Peino R,et al.Gender differences in both spontaneous and stimulated leptin secretion by human omental adipose tissue in vitro:dexameshasone and estradiol stimulate leptin release in women,but not in men[J].J Clin Endcrinol Metab,1998,83:2149-2155.
[40]Wabitsch M,Blum WF,Muche R,et al.Contribution of and gene to gender difference in leptin production in obese children and adolescents[J].J Clin Invest,1997,100:808-813.
[41]王遂军,贾伟平,包玉倩,等.血清脂联素与肥胖的关系[J].中华内分泌代谢杂志,2005,21(1):36-38.
[42]Wajchenberg BL.Subcutaneous and visceral adipose tissue:their relation to the metabolic syndrome[J].Endocr Rev,2000,21:697-738.
[43]Nishizawa H,Shimomura I,Kishida K,et al.Androgens decrease plasma adiponectin,an insulin-sensitizing adipocytederived protein[J].Diabetes,2002,51:2734-2741.
[44]Tsou PL,Jiang YD,Chang CC,et al.Sex-related differences between adiponectin and insulin resistance in schoolchildren[J].Diabetes Care,2004,27:308-313.
[45]Lanfranco F,Zitzmann M,Simoni M et al.Serum adiponectin levels in hypogonadal men:influence of testosterone replacement therapy[J].Clinical Endocrinology,2004,60:500-507.
[46]Huang KC,Lin RCY,Kormas N,et al.Plasma leptin is associated with insulin resistance independent of age,body mass index,fat mass,lipids,and pubertal development in nondiabetic adolescents[J].International Journal of Obesity,2004,28:470-475.
[47]Valle M,Gascon F,Martos R,et al.Relationship between high plasma leptin concentrations and metabolic syndrome in obese prepubertal children[J].International Journal of Obesity,2003,27:13-18.
[48]胡静芳,吴国亭,秦利.老年代谢综合征患者血清瘦素水平与胰岛素抵抗的 研究[J].内科理论与实践,2008,3(5):335-338.
[49]Seufert J,Kieffer TJ,Leech CA,et al.Leptin suppression of insulin secretion and gene expression in human pancreatic islets:implications for the development of adipogenic diabetes mellitus[J].J Clin Endocrinol Metab,1999,84:670-676.
[50]D'Adamo M,Buongiorno A,Marcocia E,et al.Increased ob gene expression leads to elevated plasma leptin concentrations in patients with chronic primary hyperinsulinemia[J].Diabetes,1998,47:1625-1629.
[51]Cohen B,Novick D,Rubinstein M.Modulation of insulin activities by leptin[J].Science,1996,274:1185-1188.
[52]Collier GR,De Silva A,Sanigorski A,et al.Development of obesity and insulin resistance in the Israeli sand rat.Does leptin play a role[J].Ann NY Acad Sci,1997,827:50-63.
[53]Vikram NK,Misra A,Pandey RM,et al.adiponectin,insulin resistance,and C-reactive protein in postpubertal Asian Indian adolescents[J].Metabolism,2004,53:1336-1341.
[54]Kettaneh A,Heude B,Oppert JM,et al.Serum adiponectin is related to plasma high-density lipoprotein cholesterol but not to plasma insulin-concentration in healthy children:the FLVS Ⅱ study[J].Metabolism,2006,55:1171-1176.
[55]Weiss R,Dufour S,Groszmann A,et al.Low adiponectin levels in adolescent obesity:a marker of increased intramyocellular lipid accumulation[J].J Clin Endocrinol Metab,2003,88:2014-2018.
[56]MatsuzawaY,FunahashiT,Kihara S,et al.adiponectin andmetabolic syndrome[J].Arterioscler ThrombVasc Bio,2004,24(1):29-38.
[57]Yamauchi T,Kamon J,Minokoshi Y,et al.adiponectin stimulates glucose utilization and fatty-acid oxidation by activating ampactivated protein kinase[J].Nat Med,2002,8:1288-1295.
[58]Pajvani UB,Hawkins M,Combs TP,et al.Complex distribution,not absolute amount of adiponectin,correlates with thiazolidinedione mediated improvement in insulin sensitivity[J].J Biol Chem,2004,279:12152-12162.
[59]Xu A,Wang Y,Keshaw H,et al.The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice[J]. Journal of Clinical Investigation, 2003,112: 91-100.
[60] Wagner A, Simon c, Oujaa M, et al. adiponectin is associated with lipid profile and insulin sensitivity in French adolescents[J]. Diabetes & Metabolism, 2008, 34:465-471.
[61] Verges B, Petit JM, Duvillard L, et al. adiponectin is an important determinant of ApoA-I catabolism[J]. Arterioscler Thromb Vasc Biol, 2006,26: 1364-1369.
[62] Schneider JG, von Eynatten M, Schneider S, et al. Low plasma adiponectin levels are associated with increased hepatic lipase activity in vivo[J]. Diabetes Care, 2005,28: 2181-2186.
[63] Petersen KF, Oral EA, Dufour S, et al. Leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy[J]. J Clin Invest, 2002, 109: 1345-1350.
[64] Simha V, Szczepaniak LS, Wagner AJ, et al. Effect of leptin replacement on intrahepatic and intramyocellular lipid content[J]. Metabolism, 2006, 55: 1171-1176.
[65] Steinberg GR, Parolin ML, Heigenhauser GJ, et al. Leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance[J]. Am J Physiol Endocrinol Metab, 2002,283(1): E187-E192.
[66] Huang h, Dedousis N, Bandi A, et al. Liver Triglyceride Secretion and Lipid Oxidative Metabolism Are Rapidly Altered by Leptin in Vivo [J]. Endocrinology, 2006,147(3): 1480-1487.
[67] Sudi KM, Gallistl S, Weinhandl G, et al. No evidence for leptin as an independent associate of blood pressure in childhood and juvenile obesity[J]. J Pediatr Endocrinol Metab, 2000, 13: 513-521.
[68] Adamczak M, Wiecedil T, Funahashi T, et al. Decreased plasma adiponectin concentration in patients with essential hypertension[J]. Am J Hypertens, 2003, 16: 72-75.
[69] Agata J, Masuda A, Takada M, et al. High plasma immunoreactive leptin level in essential hypertension[J]. Am J Hypertens, 1997, 10: 1171-1174.
[70]Kokot F,Adamczak M,Wiecek A,et al.Does leptin play a role in the pathogenesis of essential hypertension?[J].Kidney Blood Press Res,1999,22:154-160.
[71]Suter PM,Locher R,Hasler E,et al.Is there a role for the ob gene product leptin in essential hypertension?[J].Am J Hypertens,1998,11:1305-1311.
[72]Almeida PB,Gimeno SG,Freire RD,et al.Leptin is not associated independently with hypertension in Japanese-Brazilian women[J].Braz J Med BiolRes,2006,39(1):99-105.
[73]Maryam G,Hossein F,Alireza M,et al.Serum Leptin Levels and Hypertension in Iranian Obese Children[J].The Endocrinologist,2007,17:258-261.
[74]Ohashi K,Kihara S,Ouchi N,et al.adiponectin replenishment ameliorates obesity-related hypertension[J].Hypertension,2006,47(6):1108-1116.
[75]张美仙,米杰,赵小元,等.瘦素和脂联素在儿童肥胖相关性高血压发病中的作用[J].中国循证儿科杂志,2008,13(2):96-102.
[76]Cesari M,Pessina AC,Zanchetta M,et al.Low plasma adiponectin is associated with coronary artery disease but not with hypertension in high risk nondiabetic patients[J].J Intern Med,2006,260:474-483.
[77]Mallamaci F,Zoccali C,Cuzzola F,et al.adiponectin in essential hypertension[J].J Nephrol,2002,15:507-511.
[78]罗勇,李小平,覃数,等.超重及肥胖患者血清抵抗素与脂联素水平[J].中华高血压杂志.2007,15(6):505-506.
[79]Yang WS,Lee WJ,Funahashi T,et al.Plasma adiponectin levels in overweight and obese Asians[J].Obes Res,2002,10:1104-1110.
[80]Hrang KC,Chen CL,Chuang LM,et al.Plasma adiponectin Levels and Blood Pressures in Nondiabetic Adolescent Females[J].J Clin Endocrinol Metab,2003,88:4130-4134.
[81]Adamczak M,Wiecedil,Funahashi T,et al.Decreased plasma adiponectin concentration in patients with essential hypertension[J].Am J Hypertens,2003,16:72-75.
[82]徐轶群,季成叶,马军,等.女性青少年血清脂联素水平与血压的关系研究[J].中国学校卫生,2007,28(4):292-293.
[83]Ogawa Y,Masuzaki H,Hosoda K,et al.Increased glucose metabolism and insulin sensitivity in Transgenic SkinnyMice over expressing leptin[J].Diabetes,1999,48:1822-1829.
[84]Combs TP,Berg AH,Scherer PE,et al.Endogenous glucose production is inhibited by the adipose-derived protein Acrp30[J].J Clin Invest,2001,108:1875-1881.
[85]Wu X,Motoshima H,Mahadev K,et al.Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes[J].Diabetes,2003,52:1355-1363.
[86]Christoph H,Lorenz R,Guenter H,et al.Low serum adiponectin is indepen-dently associated with both the metabolic syndrome and angiographically determined coronary atherosclerosis[J].Clinica Chimica Acta,2007,383:97-102.
[87]Gilardini L,McTernan PG,Girola A,et al.adiponectin is a candidate marker of metabolic syndrome in obese children and adolescents[J].Atherosclerosis,2006,189:401-407.
[88]Gabriel QS,Martha LC,Mrc JW,et al.adiponectin Independently Predicts Metabolic Syndrome in Overweight Latino Youth[J].J Clin Endocrinol Metab,2007,92:1809-1813.
[89]Anahita H,Hossein F,Alireza M,et al.Metabolic Syndrome and Leptin Concentrations in Obese Children[J].Indian J Pediatr,2006,73(7):593-596.
[90]张建,华琦主编.代谢综合征[M].人民卫生出版社,2003,10:8-11.
[1]Ford ES,Giles WH,Dietz WH et al.Prevalence of the metabolic syndrome among US adults:findings from the third National Health and Nutrition Examination Survey[J].JAMA,2002,287:356-359.
[2]顾东风,Reynold K,杨文杰,等.中国成人代谢综合征的患病率[J].中华糖尿病杂志,2005,13(3):181-186.
[3]Cook S,Weitzman M,Auinger P,et al.Prevalence of a Metabolic Syndrome Phenotype in Adolescents[J].Arch pediatr Adolesc Med,2003;157:821-827.
[4]Cruz M,Weigensbeg M,Huang T,et al.The Metabolic Syndrome in Oveweight Hispanic Youth and the Role of Insulin Sensitivity.[J]Clin Endocrinol Metab,2004,89(1):108-113.
[5]米杰,程红.儿童肥胖和代谢综合征[J].中国医刊,2007,42(5):17-20.
[6]Ogden CL,Carroll MD,Curtin LR,et al.Prevalence of overweight and obesity in the United States,1999-2004[J].JAMA,2006,295:1549-1555.
[7]米杰,程红,侯冬青,等.北京市2004年2-18岁儿童青少年超重和肥胖流行现状[J].中华流行病学杂志,2006,27(6):469-474.
[8]Zhang Y,Proenca R,Maffei M,et al.Positional cloning of the mouse obese gene and its human homologue[J].Nature(Lond),1994,372:425-432.
[9]Muoio DM,Lynis DG.Peripheral metabolic actions of leptin[J].Best Pract Res Clin Endocrinol Metab,2002,16:653-666.
[10]柏晓璐,戴秋艳.瘦素与代谢综合征[J].内科理论也实践,2008,3(3):207-210.
[11]Gura T.leptin not impressive in clinical trial[J].Science,1999,286:881-882.
[12]Haj FG,Zabolotny JM,Kim YB,et al.Liver-specific proteintyrosine phosphatase 1B(PTP1B) re-expression alters glucose homeostasis of PTP1B-/-mice[J].J Biol Chem,2005,280:15038-15046.
[13]Scarpace PJ,Matheny M,Tumer N,et al.leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats[J].Diabetologia,2005,48:1075-1083.
[14] Shimomura I, Hammer RE, Ikemoto S, et al. leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy[J]. Nature, 1999, 401:73-76.
[15] Petersen KF, Oral EA, Dufour S, et al. leptin reverses insulin resistance and hepatic steatosis in patients with severe lipodystrophy[J]. J Clin Invest, 2002, 109: 1345-1350.
[16] Ogawa Y, Masuzaki H, Hosoda K, et al. Increased glucose metabolism and insulin sensitivity in Transgenic Skinny Mice overexpressing leptin.Diabetes[J]. 1999,48:1822-1829.
[17] Steinberg GR, Bonen A, Dyck DJ. Fatty acid oxidation and triacylglycerol hydrolysis are enhanced after chronic leptin treatment in rats[J]. Am J Physiol, 2002, 282: E593-E600.
[18] Minokoshi Y, Kahn BB. Role of AMP-activated protein kinase in leptin induced fatty acid oxidation in muscle[J]. Biochem Soc Trans, 2003, 31: 196-201.
[19] Atkinson LL, Fischer MA, Lopaschuk GD. leptin activates cardiac fatty acid oxidation independent of changes in the AMP-activated protein kinaseacetyl- CoA carboxylase-malonyl-CoA axis[J]. J Biol Chem, 2002,277: 29424-29430.
[20] Huang W, Dedousis N, Bhatt BA, et al. Impaired activation of phosphatidylin- ositol 3-kinase by leptin is a novel mechanism of hepatic leptin resistance in diet-induced obesity[J]. J Biol Chem, 2004,279: 21695-21700.
[21] Huang h, Dedousis N, Bandi A, et al. Liver Triglyceride Secretion and Lipid Oxidative Metabolism Are Rapidly Altered by leptin in Vivo [J]. Endocrinology, 2006,147(3): 1480-487.
[22] Steinberg GR, Parolin ML, Heigenhauser GJ, et al. leptin increases FA oxidation in lean but not obese human skeletal muscle: evidence of peripheral leptin resistance[J]. Am J Physiol Endocrinol Metab, 2002,283(1): E187-E192.
[23] Carlyle M, Jones OB, Kuo JJ, et al. Chronic Cardiovascular and Renal Actions of leptin: Role of Adrenergic Activity[J]. Hypertension, 2002, 39: 496-501.
[24] Sympathetic Overdrive and Cardiovascular Risk in the Metabolic Syndrome[J]. Hypertens Res, 2006,29: 839-847.
[25] Correia ML, Haynes WG, Rahmouni K, et al. The concept of selective leptin resistance: evidence from agouti yellow obese mice[J]. Diabetes, 2002, 51(2): 439-442.
[26] Rahmouni K, Morgan DA, Morgan GM, et al. Role of selective leptin resistance in diet-induced obesity hypertension[J]. Diabetes, 2005, 54:2012-2018.
[27] Lembo G, Vecchione C, Fratta L, et al. leptin induces direct vasodilation through distinct endothelial mechanisms[J]. Diabetes, 2000,49(2): 293-297.
[28] Fruhbeck G. Pivotal role of nitric oxide in the ocntrol of Blood Pressure after leptin administration[J]. Diabetes, 1999,48: 903-908.
[29] Mackintosh RM, Hirsch J. The effects of leptin administration in nonobese human subjects[J]. Obes Res, 2001 ,9:462-469.
[30] Agata J, Masuda A, Takada M, et al. High plasma immunoreactive leptin level in essential hypertension[J]. Am J Hypertens, 1997,10: 1171-1174.
[31] Serum leptin Levels and Hypertension in Iranian Obese Children[J]. The Endocrinologist, 2007,17: 258-261.
[32] Lee MJ, Fried SK. Multilevel regulation of leptin storage, turnover, and secretion by feeding and insulin in rat adipose tissue[J]. J Lipid Res, 2006,47(9): 1984-1993.
[33] Muzumdar R, Ma X, Yang X, et al. Physiologic effect of leptin on insulin secretion is mediated mainly through central mechanisms[J]. FASEB J, 2003, 17:1 130-1132.
[34] D'Adamo M, Buongiorno A, Marcocia E, et al. Increased ob gene expression eads to elevated plasma leptin concentrations in patients with chronic primary hyperinsulinemia [J]. Diabetes, 1998,47:1625-1629.
[35] Coralia P, Carmen FG, Teresa FA, et al. leptin impairs insulin signaling in rat adipocytes[J]. Diabetes, 2004, 53(2): 347-353.
[36] Zhao YF, Chen C. Regulation of pancreatic β-cell function by adipocytes [J]. Sheng Li Xue Bao, 2007, 59(3): 247- 252.
[37] Bodary PF, Westrick RJ, Wickenheiser KJ, et al. Effect of leptin on Arterial Thrombosis Following Vascular Injury in Mice[J]. JAMA, 2002, 287: 1706-1709.
[38]Barouch LA,Berkowitz DE,Harrison RW,et al.Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice[J].Circulation,2003,108(6):754-759.
[39]庄向华,董砚虎,许爱梅,等.糖尿病一级亲属脂联素和瘦素与胰岛素抵抗的相关性[J].中华糖尿病杂志,2005,13(1):8-10.
[40]Circulating leptin levels predict the development of metabolic syndrome in middle-aged men:an 8-year follow-up study[J].J Hypertens,25:1671-1677.
[41]Yamauchi T,Kamon J,Ito Y,et al.Cloning of adiponectin receptors that mediate antidiabetic metabolic effects[J].Nature,2003,423:762-769.
[42]Halleux CM,Takahashi M,Delporte ML.Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue[J].Biochem Biophys Res Commun,2001,16(288):1102-1107..
[43]Nishizawa H,Shimomura I,Kishida K,et al.Androgens decrease plasma ADIPOnectin,an insulin-sensitizing adipocytederived protein[J].Diabetes,2002,51:2734-2741.
[44]Yu JG,Javorchi S,Hevener AL,et al.The effect of thiazolidinediones on plasma adiponectin levels in normal,obese,and type 2 diabetic subjects[J].Diabetes,2002,51(8):2968-2974.
[45]唐金凤,杨颖,汪启迪,等.血清脂联索水平与肥胖度的关系[J].中华内分泌代谢杂志,2003,19(2):166-168.
[46]Yatagai T,Nagasaka S,Taninguchi A,et al.Hypoadiponectinemia is associated with visceral fat accumulation an insulin resistance in Japanese marl with type 2diabetes mellitus[J].Metabolism,2003,52(8):1274-1278.
[47]Berg AH,Combs TP,Du X,et al.The adipocytesecreted protein Acrp30enhances hepatic insulin action[J].Nat Med,2001,7:947-953.
[48]Nawrocki AR,Rajala MW,Tomas E,et al.Mice lacking adiponectin show decreased hepatic insulin sensitivity and reduced responsiveness to peroxisome proliferatoractivated receptor gamma agonists[J].J Biol Chem,2006,281:2654-2660.
[49]Tomas E,Tsao TS,Saha AK,et al.Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation[J]. Proc Natl Acad Sci U S A, 2002, 99: 16309-16313.
[50] Berg AH, Combs TP, Du X, et al. The adipocyte secreted protein Acrp30 enhances hepatic insulin action[J]. Nat Med, 2001,7: 947-953.
[51] Yamauchi T, Kamon J, Waki H, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J]. Nat Med, 2001,7: 941-946.
[52] Xu A, Wang Y, Keshaw H, et al. The fat-derived hormone adiponectin alleviates alcoholic and nonalcoholic fatty liver diseases in mice[J]. Journal of Clinical Investigation, 2003,112: 91-100.
[53] Stefan N, Stumvoll M, Vozarova B, et al. Plasma adiponectin and endogenous glucose production in humans[J]. Diabetes Care, 2003, 26: 3315-3319.
[54] Miyazaki Y, Mahankali A, Wajcberg E, et al. Effect of pioglitazone on circulating adipocytokine levels and insulin sensitivity in type 2 diabetic patients[J]. J Clin Endocrinol Metab, 2004, 89: 4312-4319.
[55] Bugianesi E, Pagotto U, Manini R, et al. Plasma adiponectin in nonalcoholic fatty liver is related to hepatic insulin resistance and hepatic fat content, not to liver disease severity[J]. J Clin Endocrinol Metab, 2005, 90: 3498-3504.
[56] Yamauchi T, Kamon J, Minokoshi Y, et al. adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase[J]. Nat Med, 2002, 8: 1288-1295.
[57] Yamauchi T, Kamon J, Minokoshi Y, et al. adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase[J]. Nat. Med, 2002, 8: 1288-1295.
[58] Matsuzawa Y, Funahashi T, Kihara S, et al. adiponectin and metabolic syndrome[J]. Arterioscler ThrombVasc Biol, 2004, 24(1): 29-38.
[59] Hotta K, Funahashi T, Bodkin NL, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesusmonkeys[J]. Diabetes,2001,50.(5):1126-1133.
[60]Yamauchi T,Kamon J,Waki H,et al.The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity[J].Nat.Med,2001,7:941-946.
[61]Goldstein BJ,Scalia R.adiponectin:a novel adipokine linking adipocytes and vascular function[J].J Clin Endocrinol Metab,2004,89(6):2563-2568.
[62]Ohashi K,Kihara S,Ouchi N,et al.adiponectin replenishmentameliorates obesity-related hypertension[J].Hypertension,2006,47(6):1108-1116.
[63]徐轶群,季成叶,马军,等.女性青少年血清脂联素水平与血压的关系研究[J].中国学校卫生,2007,28(4):292-293.
[64]Ouchi N,Walsh K.adiponectin as an anti-inflammatory factor[J].Clin Chim Acta,2007,380:24-30.
[65]Ouchi N,Kihara S,Arita Y,et a.l adipocyte-derived plasma protein,adiponectin,suppresses lipid accumulation and classA scavenger receptor expression in humanmonocyte-derived macrophages[J].Circulation,2001,103(8):1057-1063.
[66]Kumada M,Kihara S,Ouchi N,et al.adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages[J].Circulation,2004,109:2046-2049.
[67]Matsuda M,Shimomura I,Sata M,et al.Role of adiponectin in preventing vascular stenosis-The missing link of adipo-vaseular axis[J].J BiolChem,2002,277(40):37487-37491.
[68]Okamoto Y,Kihara S,Ouchi N,et al.ADIPOnectin reduces atherosclerosis in apolipoprotein E-deficient mice[J].Circulation,2002,106:2767-2770.
[69]Yamauchi T,Kamon J,Waki H,Imai Y,et al.Globular adiponectin protected ob/ob mice from diabetes and apoE deficient mice from atherosclerosis[J].J Biol Chem,2002,278:2461-2468.
[70]Shimabukuro M,Higa N,Asahi T,et al.Hypoadiponectinemia is closely linked to endothelial dysfunction in man[J].J Clin Endocrinol Metab,2003,88:3236-3240.
[71]Tan KCB,Xy A,ChowWS,et al.Hypoadiponectinemia is associated with impaired endothelium-dependent vasodilation[J].J Clin Endocrinol Metab,2004,89:765-769.
[72]Pilz S,Horejsi R,Miler R,et al.Early atherosclerosis in obese juveniles is associated with low serum levels of adiponectin[J].J Clin EndocrinolMetab,2005,90(8):4792-4796.
[73]Lihn AS,Ostergard T,Nyholm B,et al.ADIPOnectin expression in adipose tissue is reduced in first-degree relatives of type 2 diabetic patients[J].Am J Physiol Endocrinol Metab,2003,284:E443-E448.
[74]Daimon M,Oizumi T,Saitoh T,et al.Decreased serum levels of adiponectin are a risk factor for the progression to type 2 diabetes in the Japanese population-The Funagata study[J].Diabetes Care,2003,26(7):2015-2020.
[75]Haluzik M,Pafizkova J,Haluzik M,et al.adiponectin and its role in the obesity-induced insulin resistance and related complications[J].PhysiolRes,2004,53(2):123-129.