代谢综合征患者脂肪因子的变化及意义
摘要
目的代谢综合征(metabolic syndrome,MS)是以中心性肥胖、胰岛素抵抗、高血压、高甘油三酯血症、低高密度脂蛋白胆固醇、糖耐量下降或2型糖尿病为主要特征的症候群。近年研究发现,脂肪组织不仅能储存能量,还具有内分泌功能。常见的脂肪组织分泌的活性物质有: 1.脂肪因子,如瘦素、脂联素、抵抗素;2.炎症因子,如肿瘤坏死因子-α(tumor necrosis factor-α, TNF-α),白细胞介素-6 (interleukin-6, IL-6),白细胞介素-1(interleukin-1, IL-1),单核细胞趋化蛋白-1 (monocyte chemoattractant protein-1, MCP-1),C反应蛋白(C-reactive protain, CRP)等;3.血栓形成调节因子,如纤溶酶原激活物抑制因子-1(plasminogen activator inhibitor-1, PAI-1),纤维蛋白原(fibrinogen)等。脂肪组织分泌的脂肪因子在代谢综合征的发病中的作用近年来受到广泛关注。本研究通过检测健康体检者血清脂联素、瘦素,探讨代谢综合征患者血清脂联素、瘦素水平的变化及意义,以及血清脂联素、瘦素与体重指数、腰围、腰臀比、收缩压、舒张压、空腹血糖、血清总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇的相关性。
方法参照美国国家胆固醇教育计划成人治疗组第三次指南(NCEP-ATPⅢ)提出的代谢综合征诊断标准[1],入选健康体检中首次发现代谢综合征组患者36例,其中男性16例,女性20例,年龄40岁～71岁,平均年龄59.2±8.2岁,设为代谢综合征组,同期健康体检正常人37例设为健康对照组,其中男性19例,女性18例,年龄40岁～70岁,平均年龄60.3±8.5岁。测定入选对象身高、体重、体重指数、腰围、臀围、腰臀比、血压和生化指标:空腹血糖、总胆固醇、血清甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇。用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)测定血清脂联素、瘦素水平。用SPSS13.0软件对数据进行统计学分析,P<0.05为有统计学意义。
结果
1.代谢综合征组血清脂联素低于健康对照组(1.71±1.73mg/L与2.80±1.80mg/L, P<0.05)。代谢综合征组血清瘦素与健康对照组比较未达到统计学意义(0.94±0.64ug/L与1.22±0.83ug/L, P>0.05)。
2.脂联素与腰围、臀围、腰臀比、体重指数、收缩压、舒张压、空腹血糖、总胆固醇、甘油三脂、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇的直线相关分析结果:①代谢综合征组:脂联素与总胆固醇(r=-0.432, P=0.009)、低密度脂蛋白胆固醇(r=-0.404, P=0.014)呈负相关。②男性组:脂联素与总胆固醇(r=-0.369, P=0.027)、低密度脂蛋白胆固醇(r=-0.381, P=0.022)、体重指数(r=-0.370, P=0.026)呈负相关。③女性组:脂联素与收缩血压(r=-0.348, P=0.032)、总胆固醇(r=-0.322, P=0.049)呈负相关。④代谢综合征组控制年龄、性别因素的偏回归分析显示:脂联素与总胆固醇(r=-0.435, P=0.010)、低密度脂蛋白胆固醇(r=-0.435, P=0.010)呈负相关。
3.瘦素与腰围、腰臀比、体重指数、收缩压、舒张压、空腹血糖、总胆固醇、甘油三脂、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇的直线相关分析结果显示:瘦素与各个测定指标无相关性。
4.以脂联素为应变量,以腰围、腰臀比、体重指数、收缩压、舒张压、空腹血糖、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密脂蛋白胆固醇、瘦素为变量,进行多元线性逐步回归分析,结果总胆固醇进入方程,脂联素与总胆固醇之间存在线性关系,线性回归方程为y=5.604-0.638X, P<0.01。
结论
1.健康体检首次诊断的代谢综合征患者血清脂联素水平降低。
2.血清脂联素与总胆固醇呈负相关关系。血清脂联素与血压、血脂、代谢指标的相关关系存在性别差异。脂联素水平与其他测定指标的相关分析:①代谢综合征组:脂联素与总胆固醇、低密度脂蛋白胆固醇呈负相关。②男性组:脂联素与总胆固醇、低密度脂蛋白胆固醇、体重指数呈负相关。③女性组:脂联素与收缩血压、总胆固醇呈负相关。④代谢综合征组控制年龄、性别因素的偏回归分析显示:脂联素与总胆固醇、低密度脂蛋白胆固醇呈负相关。
Objective Metabolic syndrome is incorporates into a single entity, insulin resistance and its associated cluster of related cardiovascular metabolic risk factors including essential hypertension, central obesity, hyper-triglyceridemia, hypo-high density lipoprotein cholesterol, impaired glucose tolerance and type 2 diabetes mellitus. Recent studies show that adipose tissue is not simply storage of energy, but is an active endocrine organ. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like tumor necrosis factor-a(TNF-a), interleukin-6(IL-6), interleukin-1(IL-1), monocyte chemo attractant protein (MCP-1), C reactive protein(CRP), et al, and some thrombogenesis factors, such as plasminogen activator inhibitor-1(PAI-1), fibrinogen, et al. The adipokine secreted by adipose tissue, such as adiponectin, leptin, resistin, play important roles in the pathogenesis of metabolic syndrome. This research is to investigate the change of adipokine levels in patients with metabolic syndrome, and their relationship with the components of metabolic syndrome. The aim of this study is also to detect the relationship between serum adiponectin, leptin and body mass index, waist circumference, waist to hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose(FBG), serum total cholesterol(TC), triglyceride (TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C).
Methods: Based on standards of NECP-ATPIII, 36 MS patients who were first diagnostic in the health examination were selected as MS group [20 women and 16men; mean (±SD) age, 59.2±8.2 years] and 37 healthy subjects as control group [18 women and 19 men; mean (±SD) age, 60.3±8.5 years]. After measured the anthropometric parameters: the height, weight ,waist circumference, hip circumference, the waist to hip ratio, systolic blood pressure and diastolic blood pressure, the biochemical parameters of MS group and healthy control group were collected: the fasting blood glucose, serum total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol were determined. The serum adiponectin and leptin levels were measured with enzyme linked immunosorbent assay (ELISA). All analyses were performed with the use of SPSS software (version 13.0). P<0.05 shew statistical significantly different.
Result:
1. The adiponectin level of MS patents was lower significantly than healthy subjects (1.71±1.73mg/L vs. 2.80±1.80mg/L, P<0.05). It is not value significantly different between MS patents and healthy subjects in serum leptin level (0.94±0.64ug/L vs. 1.22±0.83ug/L, P>0.05).
2. In MS group, serum adiponectin concentrations were negatively correlated with the total cholesterol (r=-0.432, P=0.009), LDL-C (r=-0.404, P=0.014). In male group, serum adiponectin concentrations were negatively correlated with the total cholesterol (r=-0.369, P=0.027), LDL-C(r=-0.381, P=0.022), and body mass index (r=-0.370, P=0.026). In female group, serum adiponectin concentrations were negatively correlated with systolic blood pressure (r=-0.348, P=0.032), total cholesterol (r=-0.322, P=0.049). Controlling for the gender and age in MS group, adiponectin levels was negatively correlated with total cholesterol (r=-0.435, P=0.010) and LDL -C levels(r=-0.435, P=0.010).
3. There is no relationship between serum leptin level and other determinations.
4. The stepwise linear regression between serum adiponectin and other determinations shows that there is linear relationship between serum adiponectin and total cholesterols.
Conclusions:
1. The adiponectin level decreased in MS patients who were first diagnostic in the health examination.
2. The linear correlation between serum adiponectin and other determinations: in MS group, serum adiponectin concentrations were negatively correlated with the total cholesterol and LDL-C; in male group, serum adiponectin concentrations were negatively correlated with the total cholesterol, LDL-C, and body mass index; in female group, serum adiponectin concentrations were negatively correlated with systolic blood pressure, total cholesterol. Controlling for the gender and age in MS group, adiponectin levels was negatively correlated with total cholesterol and LDL -C.
方法参照美国国家胆固醇教育计划成人治疗组第三次指南(NCEP-ATPⅢ)提出的代谢综合征诊断标准[1],入选健康体检中首次发现代谢综合征组患者36例,其中男性16例,女性20例,年龄40岁～71岁,平均年龄59.2±8.2岁,设为代谢综合征组,同期健康体检正常人37例设为健康对照组,其中男性19例,女性18例,年龄40岁～70岁,平均年龄60.3±8.5岁。测定入选对象身高、体重、体重指数、腰围、臀围、腰臀比、血压和生化指标:空腹血糖、总胆固醇、血清甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇。用酶联免疫吸附法(enzyme linked immunosorbent assay,ELISA)测定血清脂联素、瘦素水平。用SPSS13.0软件对数据进行统计学分析,P<0.05为有统计学意义。
结果
1.代谢综合征组血清脂联素低于健康对照组(1.71±1.73mg/L与2.80±1.80mg/L, P<0.05)。代谢综合征组血清瘦素与健康对照组比较未达到统计学意义(0.94±0.64ug/L与1.22±0.83ug/L, P>0.05)。
2.脂联素与腰围、臀围、腰臀比、体重指数、收缩压、舒张压、空腹血糖、总胆固醇、甘油三脂、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇的直线相关分析结果:①代谢综合征组:脂联素与总胆固醇(r=-0.432, P=0.009)、低密度脂蛋白胆固醇(r=-0.404, P=0.014)呈负相关。②男性组:脂联素与总胆固醇(r=-0.369, P=0.027)、低密度脂蛋白胆固醇(r=-0.381, P=0.022)、体重指数(r=-0.370, P=0.026)呈负相关。③女性组:脂联素与收缩血压(r=-0.348, P=0.032)、总胆固醇(r=-0.322, P=0.049)呈负相关。④代谢综合征组控制年龄、性别因素的偏回归分析显示:脂联素与总胆固醇(r=-0.435, P=0.010)、低密度脂蛋白胆固醇(r=-0.435, P=0.010)呈负相关。
3.瘦素与腰围、腰臀比、体重指数、收缩压、舒张压、空腹血糖、总胆固醇、甘油三脂、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇的直线相关分析结果显示:瘦素与各个测定指标无相关性。
4.以脂联素为应变量,以腰围、腰臀比、体重指数、收缩压、舒张压、空腹血糖、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密脂蛋白胆固醇、瘦素为变量,进行多元线性逐步回归分析,结果总胆固醇进入方程,脂联素与总胆固醇之间存在线性关系,线性回归方程为y=5.604-0.638X, P<0.01。
结论
1.健康体检首次诊断的代谢综合征患者血清脂联素水平降低。
2.血清脂联素与总胆固醇呈负相关关系。血清脂联素与血压、血脂、代谢指标的相关关系存在性别差异。脂联素水平与其他测定指标的相关分析:①代谢综合征组:脂联素与总胆固醇、低密度脂蛋白胆固醇呈负相关。②男性组:脂联素与总胆固醇、低密度脂蛋白胆固醇、体重指数呈负相关。③女性组:脂联素与收缩血压、总胆固醇呈负相关。④代谢综合征组控制年龄、性别因素的偏回归分析显示:脂联素与总胆固醇、低密度脂蛋白胆固醇呈负相关。
Objective Metabolic syndrome is incorporates into a single entity, insulin resistance and its associated cluster of related cardiovascular metabolic risk factors including essential hypertension, central obesity, hyper-triglyceridemia, hypo-high density lipoprotein cholesterol, impaired glucose tolerance and type 2 diabetes mellitus. Recent studies show that adipose tissue is not simply storage of energy, but is an active endocrine organ. These are achieved predominantly through release of adipocytokines, which include several novel and highly active molecules released abundantly by adipocytes like leptin, resistin, adiponectin or visfatin, as well as some more classical cytokines released possibly by inflammatory cells infiltrating fat, like tumor necrosis factor-a(TNF-a), interleukin-6(IL-6), interleukin-1(IL-1), monocyte chemo attractant protein (MCP-1), C reactive protein(CRP), et al, and some thrombogenesis factors, such as plasminogen activator inhibitor-1(PAI-1), fibrinogen, et al. The adipokine secreted by adipose tissue, such as adiponectin, leptin, resistin, play important roles in the pathogenesis of metabolic syndrome. This research is to investigate the change of adipokine levels in patients with metabolic syndrome, and their relationship with the components of metabolic syndrome. The aim of this study is also to detect the relationship between serum adiponectin, leptin and body mass index, waist circumference, waist to hip ratio, systolic blood pressure, diastolic blood pressure, fasting blood glucose(FBG), serum total cholesterol(TC), triglyceride (TG), high density lipoprotein cholesterol(HDL-C), low density lipoprotein cholesterol(LDL-C).
Methods: Based on standards of NECP-ATPIII, 36 MS patients who were first diagnostic in the health examination were selected as MS group [20 women and 16men; mean (±SD) age, 59.2±8.2 years] and 37 healthy subjects as control group [18 women and 19 men; mean (±SD) age, 60.3±8.5 years]. After measured the anthropometric parameters: the height, weight ,waist circumference, hip circumference, the waist to hip ratio, systolic blood pressure and diastolic blood pressure, the biochemical parameters of MS group and healthy control group were collected: the fasting blood glucose, serum total cholesterol, triglyceride, high density lipoprotein cholesterol, low density lipoprotein cholesterol were determined. The serum adiponectin and leptin levels were measured with enzyme linked immunosorbent assay (ELISA). All analyses were performed with the use of SPSS software (version 13.0). P<0.05 shew statistical significantly different.
Result:
1. The adiponectin level of MS patents was lower significantly than healthy subjects (1.71±1.73mg/L vs. 2.80±1.80mg/L, P<0.05). It is not value significantly different between MS patents and healthy subjects in serum leptin level (0.94±0.64ug/L vs. 1.22±0.83ug/L, P>0.05).
2. In MS group, serum adiponectin concentrations were negatively correlated with the total cholesterol (r=-0.432, P=0.009), LDL-C (r=-0.404, P=0.014). In male group, serum adiponectin concentrations were negatively correlated with the total cholesterol (r=-0.369, P=0.027), LDL-C(r=-0.381, P=0.022), and body mass index (r=-0.370, P=0.026). In female group, serum adiponectin concentrations were negatively correlated with systolic blood pressure (r=-0.348, P=0.032), total cholesterol (r=-0.322, P=0.049). Controlling for the gender and age in MS group, adiponectin levels was negatively correlated with total cholesterol (r=-0.435, P=0.010) and LDL -C levels(r=-0.435, P=0.010).
3. There is no relationship between serum leptin level and other determinations.
4. The stepwise linear regression between serum adiponectin and other determinations shows that there is linear relationship between serum adiponectin and total cholesterols.
Conclusions:
1. The adiponectin level decreased in MS patients who were first diagnostic in the health examination.
2. The linear correlation between serum adiponectin and other determinations: in MS group, serum adiponectin concentrations were negatively correlated with the total cholesterol and LDL-C; in male group, serum adiponectin concentrations were negatively correlated with the total cholesterol, LDL-C, and body mass index; in female group, serum adiponectin concentrations were negatively correlated with systolic blood pressure, total cholesterol. Controlling for the gender and age in MS group, adiponectin levels was negatively correlated with total cholesterol and LDL -C.
引文
1 Expert panel on detection, evaluation, and treatment of high blood cholesterol in adults. Executive summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). JAMA. 2001, 285(19):2486-2497
2 Friedman J M, Halaas J L. Leptin and the regulation of body weight in mammals.Nature. 1998, 395(6704): 763- 770
3 Huang LU, Cai LI. Leptin a multifunctional hormone. Cell Res. 2000, 10(2):81-92
4 张广文, 赵平, 杨思进.代谢综合征的研究新进展.心血管病学进展. 2007, 28(4): 4-6
5 David E. Moller, Keith D. Kaufman. Metabolic syndrome: a clinical and molecular perspective. Annu Rev Med. 2005, 56:45-62
6 王鸿燕,林朱淼. 脂联素与 PPARγ 关系的研究进展. 国外医学内分泌分册. 2004, 24 (3):181
7 Stephan CM, L azar MA. Resist in and obesity associated insulin resistance.Trends Endocrinal Metab. 2002, 13 (1): 18-23
8 Peake PW, Kriketos AD, Campbell LV, et al. The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals. Eur J Endocrinol. 2005, 153(3):409-417
9 Merja Santaniemi, Y Antero Kesaniemi, Olavi Ukkola. Low plasma adiponectin concentration is an indicator of the metabolic syndrome.Eur J Endocrinol. 2006, 155(5): 745-750
10 Kopp HP, Krzyzanowska K, Mohlig M, et al. Effects of marked weight loss on plasma levels of adiponectin, markers of chronic sub clinical inflammation and insulin resistance in mobility obesity women. Int J Obes. 2005, 29 (7): 766 - 771
11 Yokoyama H, Emoto M, Mori K, et al. Plasma adiponectin level is associated with insulin - stimulated no oxidative glucose disposal. J Clin Endocrinal Metab. 2006, 91(1): 290 -294
12 Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002, 277(29): 25863-25866
13 Tanida M, Shen J, HoriiY, et al. Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats. Exp Biol Med. 2007, 232(3):390-397
14 Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002, 8(7): 731-737
15 毋淑珍.赵洛.沙杨文等.原发性高血压患者血清脂联素水平及与血压、胰岛素抵抗的关系. 中国心血管病研究杂志. 2007, 5 (6): 414 - 416
16 宋玲莉, 于春秋, 张丽君等,高血压患者血清抵抗素和脂联素水平的研究.心血管康复医学杂志. 2007, 16(1): 43- 45
17 Geffroy S, De Vos P, Staels B, et al. Localization of the human OB gene (OBS) to chromosome 7q32 by fluorescence in situ hybridization. Genomics. 1995, 28(3): 603-604
18 Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin. the classical, resistin. the controversial, adiponectin. the promising, and more to come. Best Pract Res ClinEndocrinol Metab. 2005, 19(4): 525-546
19 Brzozowski T, Konturek PC, Konturek SJ, et al. Role of prostaglandins in gastro protection and gastric adaptation. J Physiol Pharmacol. 2005, 56(Suppl 5): 33-55
20 Nawrot-Porabka K, Jaworek J, Leja-Szpak A, et al. Leptin is able to stimulate pancreatic enzyme secretion via activation of duodeno-pancreatic reflex and CCK release. J Physiol Pharmacol. 2004, 55(Suppl 2): 47-57
21 Konturek PC, Brzozowski T, Burnat G, et al. Role of brain-gut axis in healing of gastric ulcers. J Physiol Pharmacol. 2004; 55(2):179-192
22 Konturek SJ, Konturek JW, Pawlik T, et al. Brain-gut axis and its role in the control of food intake. J Physiol Pharmacol. 2004, 55(2):137-154
23 Konturek SJ, Pepera J, Zabielski K, et al. Brain-gut axis in pancreatic secretion and appetite control. J Physiol Pharmacol. 2003, 54: 293-317
24 Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997, 387(6636): 903-908
25 Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002, 110(8): 1093-1103
26 Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight andobese humans. N Engl J Med. 1996, 334(5): 292-295
27 Kim S, Whelan J, Claycombe K, et al. Angiotensin II increases leptin secretionby 3T3-L1 and human adipocytes via a prostaglandin-independent mechanism. J Nutr. 2002, 132(6): 1135-1140
28 Kaminski T, Smolinska N, Gajewska A, et al. Leptin and long form of leptin receptor genes expression in the hypothalamus and pituitary during the luteal phase and early pregnancy in pigs. J Physiol Pharmacol. 2006, 57(1): 95-108
29 Beltowski J, Marciniak A, Wojcicka G. Leptin decreases renal medullary Na (+) K (+)-ATPase activity through phosphatidylinositol 3-kinase dependent mechanism. J Physiol Pharmacol. 2004, 55(2): 391-407
30 Jaworek J, Bonior J, Konturek SJ et al. Role of leptin in the control of postprandial pancreatic enzyme secretion. J Physiol Pharmacol. 2003, 54(4): 591-602
31 Ramsay JE, Ferrell WR, Crawford L, et al. Divergent metabolic and vascular phenotypes in pre-eclampsia and intrauterine growth restriction: relevance of adiposity. J Hypertens. 2004, 22(11): 2177-2183
32 Zhao Y, Sun R, You L, et al. Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochem Biophys Res Commun. 2003, 300(2): 247-252
33 Sanchez-Margalet V, Martin-Romero C, Gonzalez-Yanes C, et al. Leptin receptor (Ob-R) expression is induced inperipheral blood mononuclear cells by in vitro activation and in vivo in HIV-infected patients. Clin Exp Immunol. 2002, 129(1): 119-124
34 Fujita Y, Murakami M, Ogawa Y, et al. Leptin inhibits stress-induced apoptosis of T lymphocytes. Clin Exp Immunol. 2002, 128(1): 21-26
35 Caldefie-Chezet F, Poulin A, Tridon A, et al. Leptin: a potential regulator of polymorph nuclear neutrophil bactericidal action? J Leukoc Biol. 2001, 69(3): 414-418
36 Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol.2006, 6(10): 772-783
37 Steven R. Smith. Importance of diagnosing and treating the metabolic syndrome in reducing cardiovascular risk. Obesity. 2006, 14(Suppl) 128s-134s
38 Matsuzawa Y. Adipocytokines and metabolic syndrome. Semin Vasc Med. 2005, 5(1): 34-39
39 Rabin KR, Kamari Y, Avni I, et al. Adiponectin: linking the metabolic syndrome to its cardiovascular consequences. Expert Rev Cardiovasc Ther. 2005, 3(3): 465-471
1 Weiss R, Dziura J, Burgert TS, et al.Obesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004, 350(23): 2362-2374
2 Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol.2003, 54(4): 469-487
3 Scherer PE, Willians S, Fogliano M, et al. A novel serum protein similar to Clq produced exclusively in adipocytes. J Biol Chem, 1995,270 (45):2646-2649
4 Maeda K, Okubo K, Shimomura I, et al. cDNA cloning and expression of a novel adipose specific collagen like factor, APMl (Adipose Most abundant Gene transcript-1).Biochem Biophys Res Commun, 1996, 221(2):286-289
5 Nakano Y, Tobe T, Choi Miura NH, et al. Isolation and characterization of GBP28, a novel gelatirr binding protein purified from human plasma.J Biochem(Tokyo). 1996, 120 (4):803-812
6 Arita Y, Kihara S, Ouchi N, et al. Paradoxiael decrease of an adipose specific protein, adiponectin , in obesity. Biochem Biophys Res Commun. 1999, 257 (1): 79-83
7 Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin the classical, resistin the controversial, adiponectin the promising, and more to come. Best Pract Res Clin Endocrinol Metab. 2005, 19(4): 525-546
8 Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes: molecular structure and multimer formation of adiponectin. JBiol Chem.2003, 278(41): 40352-40363
9 Lihn AS, Pedersen SB, Richelsen B. Adiponectin: action, regulation and association to insulin sensitivity. Obes Rev. 2005, 6(1):13-21
10 Beylot M, Pinteur C, Peroni O. Expression of the adiponectin receptors AdipoR1 and AdipoR2 in lean rats and in obese zucker rats.Metabolism. 2006, 55(3):396-401
11 Woo JG, Dolan LM, Daniels SR, et al. Adolescent sex differences in adiponectin are conditional on pubertal development and adiposity. Obes Res. 2005,13(12):2095- 2101
12 Chen B, LamKS, Wang Y, et al. Hypoxia dys-regulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes. Biochem Biophys Res Commun.2006, 341(2): 549-556
13 Zhao T, Hou M, Xia M, et al. Globular adiponectin decreases leptin induced tumor necrosis factor- alpha expression bymurinemacrophages: Involvement of cAMP- PKA and MAPK pathways. Cell Immunol. 2005, 238(1):19-30
14 Kawanam i D, M aemura K, Takeda N , et al. Direct reciprocal effects of resistin and diponectin on vascular endothelial cells: a new insight into adipocytokine- endothelial cell interactions. Biochem Biophys Resommun. 2004, 314(2): 415-419
15 Lin LY, Lin CY, Su TC, et al. Angiotensin II-induced apoptosis in human endothelial cells is inhibited byadiponectin through restoration of the association between endothelial nitric oxide synthase and heat shock protein 90. FEBS Lett, 2004, 574 (13): 106-110
16 Guzik TJ, Harrison DG. Vascular NADPH oxidases as drug targets for novel antioxidant strategies. Drug Discov Today. 2006, 11(11-12): 524-533
17 Guzik TJ, Sadowski J, Guzik B, et al. Coronary artery superoxide production and noxisoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol. 2006, 26(2): 333-339
18 Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002, 277(29); 25863-25866
19 Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 . Nat Med. 2002; 8(7): 731-737
20 Nishimura K, Setoyama T, Tsumagari H, et al. Endogenous prostaglandins E (2) and F (2(alpha)) serve as an anti- apoptotic factor against apoptosis induced by tumor necrosis factor-alpha in mouse 3T3-L1 preadipocytes. Biosci Biotechnol Biochem. 2006, 70(9): 2145-2153
21 Behre CJ, Fagerberg B, Hulten LM, et al. The reciprocal association of adipocytokines with insulin resistance and C-reactive protein in clinically healthy men. Metabolism. 2005, 54(4): 439-444
22 Yamamoto Y, Hirose H, Saito I, et al. Correlation of theadipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein- cholesterol, independent of body mass index, in the Japanese population. Clin Sci (Lond). 2002, 103(2): 137-142
23 Gannage-Yared MH, Fares F, Semaan M, and et al. Circulating osteoprotegerin is correlated with lipid profile, insulin sensitivity, adiponectin and sex steroids in an ageing male population. Clin Endocrinol (Oxf). 2006, 64(6): 652-658
24 Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006, 6(10): 772-783
25 Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002, 8(7): 731-737
26 Yokota T, Meka CS, Kouro T, et al. Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase prostaglandin pathway in stromal cells. J Immunol. 2003, 171(10): 5091-5099
27 Wolf AM, Wolf D, Rumpold H, et al. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun. 2004, 323(2):630-635
28 Neumeier M, Weigert J, Schaffler A, et al. Different effects of adiponectin isoforms in human monocytic cells. J Leukoc Biol. 2006; 79(4): 803-808
29 Kim KY, Kim JK, Han SH, et al. Adiponectin is a negative regulator of NK cell cytotoxicity. J Immunol. 2006, 176(10): 5958-5964
30 Waki H, Yamauchi T, Kamon J, et al. Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endo- crinology.2005, 146(2): 790- 796
31 Fasshauer M, Paschke R, Stumvoll M, et al. Adiponectin , obesity, and cardiovascular disease. Biochem.2004, 86 (11):779-784
32 Pajvani UB, Hawk ins M , Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Bio Chem, 2004, 279 (13): 12152-12162
33 Tabara Y, Osawa H, Kawamoto R, et al. Reduced high- molecular weight adiponectin and elevated hsCRP are synergistic risk factors for metabolic syndrome in a large scale middle-aged to elderly population: the J-SHIPP study.J Clin Endocrinol Metab. 2008, 93(3):715-722
34 Verges B, Petit JM, Duillad L, et al. Adiponectin is an important determinant of apoA-I catabolism. Arterioscler Thrombo Vasc Bio l, 2006, 26 (6): 1364-1369
35 Kobayashi M, Ohno T, Kawada T, et al. Serum adiponectin concentration: it’s correlation with diabetes-related traits and quantitative trait loci analysis in mouse SMXA recombinant inbred strains. Biosci Biotechnol Biochem.2006, 70(3):677-683
36 von-EynattenM , Hamann A , TwardellaD, et al. Relationship of adiponectin with markers of systemic inflammation, atherogenic dyslipidemia, and heart failure in patients with coronary heart disease. Clin Chem. 2006, 52 (5): 853-859
37 Xu A, Yin S, Wong L, et al. Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus protease inhibitor ritonavir in mice. Endocrinology. 2004, 145(2): 487-494
38 Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002; 277(29): 25863-25866
39 Yoon MJ, Lee GY, Chung JJ, et al. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor-α. Diabetes.2006, 55(9):2562-2570
40 Mori Y, Otabe S, Dina C, et al. Genome wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p. Diabetes. 2002, 51(4): 1247-1255
41 Kissebah AH, Sonnenberg GE, Myklebust J, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of metabolic syndrome. Proc Natl Acad Sci USA 2000, 97(26):14478-14483
42 Vionnet N, Hani El-H, Dupont S, et al. Genomewide search fortype 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2 diabetes locus on chromosome 1q21-q24. Am J Hum Genet. 2000, 67(6):1470-1480
43 Hara K, Boutin P, Mori Y, et al.Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes.2002, 51(2):536-540
44 Hara K, Yamauchi T, Kadowaki T.Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans. Curr Diab Rep.2005, 5(2):136-140
45 Hara K, Horikoshi M, Yamauchi T, et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care.2006, 29(6):1357-1362
46 Fisher FF, Trujillo ME, Hanif W, et al. Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia. 2005, 48(6):1084-1087
47 Miura A, Kajita K, Ishizawa M, et al. Inhibitory effect of ceramide on insulin-induced protein kinase Czeta translocation in rat adipocytes. Metabolism. 2003, 52(1): 19-24
48 Matsuzawa Y, Funahashi T, Kihara S, et al. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2004, 24(1): 29-33
49 Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000, 96(5): 1723-1732
50 Matsuda M, Shimomura I, Sata M, et al. Role of adiponectin in preventing vascular stenosis. J Biol Chem. 2002, 277(40): 37487-37491
51 Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002, 106(22): 2767-2770
52 Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens,negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000; 96(5):1723-1732
53 Hotta K, Funahashi T, Bodkin NL, et al. Circulation concentrations of the adipocyte protein adiponectin are decreased in parrallelv with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabe-tes 2001; 50(5):1126-1133
54 Yoshihisa O, Shinji K, Noriyuki O, et al. Adiponectin reduces atherosclerosis in apolipo-protein E-deficient mice. Circulation. 2002; 106(22):2767-2770
55 Yamachi T, Kamon J, Waki H, et al. Globular adiponectin protects ob/ob mice from diabetes and Apo E-deficient mice format herosclerosis. J Biol Chem. 2003; 278(4):2461-2468
56 Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasmaprotein, adiponectin, suppresses lipid accumulation and class A scavengerreceptor expression in human monocyte-derived macrophages. Circulation.2001; 103(8):1057-1063
57 Otsuka F, Sugiyama S, Kojima S, et al. Plasma adiponectin levels are associated with coronary lesion complexity in men with coronary artery disease. J Am Coll Cardiol.2006, 48(6): 1155-1162
58 Kato H, Kashiwagi H, Shiraga M, et al. Adiponectin act as an endogenous anti-thrombotic factor. Arteriosclerosis Thrombotic Vascular Biol.2006, 26 (1): 224-230
59 Shibata R, Sato K, Pimentel DR, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005, 11(10):1096-1103
60 Kojima S, Funahashi T, Sakamoto T, et al. The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction. Heart. 2003, 89(6):667
61 Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003; 23(1):85-89
62 Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol.2000, 20 (6): 1595-1599
63 Pischon T, Girman CJ, Hotamisligil GS, et al. Plasmaadiponectin levels and risk of myocardial infarction in men. JAMA. 2004, 291(14):1730-1737
2 Friedman J M, Halaas J L. Leptin and the regulation of body weight in mammals.Nature. 1998, 395(6704): 763- 770
3 Huang LU, Cai LI. Leptin a multifunctional hormone. Cell Res. 2000, 10(2):81-92
4 张广文, 赵平, 杨思进.代谢综合征的研究新进展.心血管病学进展. 2007, 28(4): 4-6
5 David E. Moller, Keith D. Kaufman. Metabolic syndrome: a clinical and molecular perspective. Annu Rev Med. 2005, 56:45-62
6 王鸿燕,林朱淼. 脂联素与 PPARγ 关系的研究进展. 国外医学内分泌分册. 2004, 24 (3):181
7 Stephan CM, L azar MA. Resist in and obesity associated insulin resistance.Trends Endocrinal Metab. 2002, 13 (1): 18-23
8 Peake PW, Kriketos AD, Campbell LV, et al. The metabolism of isoforms of human adiponectin: studies in human subjects and in experimental animals. Eur J Endocrinol. 2005, 153(3):409-417
9 Merja Santaniemi, Y Antero Kesaniemi, Olavi Ukkola. Low plasma adiponectin concentration is an indicator of the metabolic syndrome.Eur J Endocrinol. 2006, 155(5): 745-750
10 Kopp HP, Krzyzanowska K, Mohlig M, et al. Effects of marked weight loss on plasma levels of adiponectin, markers of chronic sub clinical inflammation and insulin resistance in mobility obesity women. Int J Obes. 2005, 29 (7): 766 - 771
11 Yokoyama H, Emoto M, Mori K, et al. Plasma adiponectin level is associated with insulin - stimulated no oxidative glucose disposal. J Clin Endocrinal Metab. 2006, 91(1): 290 -294
12 Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002, 277(29): 25863-25866
13 Tanida M, Shen J, HoriiY, et al. Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats. Exp Biol Med. 2007, 232(3):390-397
14 Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002, 8(7): 731-737
15 毋淑珍.赵洛.沙杨文等.原发性高血压患者血清脂联素水平及与血压、胰岛素抵抗的关系. 中国心血管病研究杂志. 2007, 5 (6): 414 - 416
16 宋玲莉, 于春秋, 张丽君等,高血压患者血清抵抗素和脂联素水平的研究.心血管康复医学杂志. 2007, 16(1): 43- 45
17 Geffroy S, De Vos P, Staels B, et al. Localization of the human OB gene (OBS) to chromosome 7q32 by fluorescence in situ hybridization. Genomics. 1995, 28(3): 603-604
18 Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin. the classical, resistin. the controversial, adiponectin. the promising, and more to come. Best Pract Res ClinEndocrinol Metab. 2005, 19(4): 525-546
19 Brzozowski T, Konturek PC, Konturek SJ, et al. Role of prostaglandins in gastro protection and gastric adaptation. J Physiol Pharmacol. 2005, 56(Suppl 5): 33-55
20 Nawrot-Porabka K, Jaworek J, Leja-Szpak A, et al. Leptin is able to stimulate pancreatic enzyme secretion via activation of duodeno-pancreatic reflex and CCK release. J Physiol Pharmacol. 2004, 55(Suppl 2): 47-57
21 Konturek PC, Brzozowski T, Burnat G, et al. Role of brain-gut axis in healing of gastric ulcers. J Physiol Pharmacol. 2004; 55(2):179-192
22 Konturek SJ, Konturek JW, Pawlik T, et al. Brain-gut axis and its role in the control of food intake. J Physiol Pharmacol. 2004, 55(2):137-154
23 Konturek SJ, Pepera J, Zabielski K, et al. Brain-gut axis in pancreatic secretion and appetite control. J Physiol Pharmacol. 2003, 54: 293-317
24 Montague CT, Farooqi IS, Whitehead JP, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature. 1997, 387(6636): 903-908
25 Farooqi IS, Matarese G, Lord GM, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest. 2002, 110(8): 1093-1103
26 Considine RV, Sinha MK, Heiman ML, et al. Serum immunoreactive-leptin concentrations in normal-weight andobese humans. N Engl J Med. 1996, 334(5): 292-295
27 Kim S, Whelan J, Claycombe K, et al. Angiotensin II increases leptin secretionby 3T3-L1 and human adipocytes via a prostaglandin-independent mechanism. J Nutr. 2002, 132(6): 1135-1140
28 Kaminski T, Smolinska N, Gajewska A, et al. Leptin and long form of leptin receptor genes expression in the hypothalamus and pituitary during the luteal phase and early pregnancy in pigs. J Physiol Pharmacol. 2006, 57(1): 95-108
29 Beltowski J, Marciniak A, Wojcicka G. Leptin decreases renal medullary Na (+) K (+)-ATPase activity through phosphatidylinositol 3-kinase dependent mechanism. J Physiol Pharmacol. 2004, 55(2): 391-407
30 Jaworek J, Bonior J, Konturek SJ et al. Role of leptin in the control of postprandial pancreatic enzyme secretion. J Physiol Pharmacol. 2003, 54(4): 591-602
31 Ramsay JE, Ferrell WR, Crawford L, et al. Divergent metabolic and vascular phenotypes in pre-eclampsia and intrauterine growth restriction: relevance of adiposity. J Hypertens. 2004, 22(11): 2177-2183
32 Zhao Y, Sun R, You L, et al. Expression of leptin receptors and response to leptin stimulation of human natural killer cell lines. Biochem Biophys Res Commun. 2003, 300(2): 247-252
33 Sanchez-Margalet V, Martin-Romero C, Gonzalez-Yanes C, et al. Leptin receptor (Ob-R) expression is induced inperipheral blood mononuclear cells by in vitro activation and in vivo in HIV-infected patients. Clin Exp Immunol. 2002, 129(1): 119-124
34 Fujita Y, Murakami M, Ogawa Y, et al. Leptin inhibits stress-induced apoptosis of T lymphocytes. Clin Exp Immunol. 2002, 128(1): 21-26
35 Caldefie-Chezet F, Poulin A, Tridon A, et al. Leptin: a potential regulator of polymorph nuclear neutrophil bactericidal action? J Leukoc Biol. 2001, 69(3): 414-418
36 Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol.2006, 6(10): 772-783
37 Steven R. Smith. Importance of diagnosing and treating the metabolic syndrome in reducing cardiovascular risk. Obesity. 2006, 14(Suppl) 128s-134s
38 Matsuzawa Y. Adipocytokines and metabolic syndrome. Semin Vasc Med. 2005, 5(1): 34-39
39 Rabin KR, Kamari Y, Avni I, et al. Adiponectin: linking the metabolic syndrome to its cardiovascular consequences. Expert Rev Cardiovasc Ther. 2005, 3(3): 465-471
1 Weiss R, Dziura J, Burgert TS, et al.Obesity and the metabolic syndrome in children and adolescents. N Engl J Med. 2004, 350(23): 2362-2374
2 Guzik TJ, Korbut R, Adamek-Guzik T. Nitric oxide and superoxide in inflammation and immune regulation. J Physiol Pharmacol.2003, 54(4): 469-487
3 Scherer PE, Willians S, Fogliano M, et al. A novel serum protein similar to Clq produced exclusively in adipocytes. J Biol Chem, 1995,270 (45):2646-2649
4 Maeda K, Okubo K, Shimomura I, et al. cDNA cloning and expression of a novel adipose specific collagen like factor, APMl (Adipose Most abundant Gene transcript-1).Biochem Biophys Res Commun, 1996, 221(2):286-289
5 Nakano Y, Tobe T, Choi Miura NH, et al. Isolation and characterization of GBP28, a novel gelatirr binding protein purified from human plasma.J Biochem(Tokyo). 1996, 120 (4):803-812
6 Arita Y, Kihara S, Ouchi N, et al. Paradoxiael decrease of an adipose specific protein, adiponectin , in obesity. Biochem Biophys Res Commun. 1999, 257 (1): 79-83
7 Koerner A, Kratzsch J, Kiess W. Adipocytokines: leptin the classical, resistin the controversial, adiponectin the promising, and more to come. Best Pract Res Clin Endocrinol Metab. 2005, 19(4): 525-546
8 Waki H, Yamauchi T, Kamon J, et al. Impaired multimerization of human adiponectin mutants associated with diabetes: molecular structure and multimer formation of adiponectin. JBiol Chem.2003, 278(41): 40352-40363
9 Lihn AS, Pedersen SB, Richelsen B. Adiponectin: action, regulation and association to insulin sensitivity. Obes Rev. 2005, 6(1):13-21
10 Beylot M, Pinteur C, Peroni O. Expression of the adiponectin receptors AdipoR1 and AdipoR2 in lean rats and in obese zucker rats.Metabolism. 2006, 55(3):396-401
11 Woo JG, Dolan LM, Daniels SR, et al. Adolescent sex differences in adiponectin are conditional on pubertal development and adiposity. Obes Res. 2005,13(12):2095- 2101
12 Chen B, LamKS, Wang Y, et al. Hypoxia dys-regulates the production of adiponectin and plasminogen activator inhibitor-1 independent of reactive oxygen species in adipocytes. Biochem Biophys Res Commun.2006, 341(2): 549-556
13 Zhao T, Hou M, Xia M, et al. Globular adiponectin decreases leptin induced tumor necrosis factor- alpha expression bymurinemacrophages: Involvement of cAMP- PKA and MAPK pathways. Cell Immunol. 2005, 238(1):19-30
14 Kawanam i D, M aemura K, Takeda N , et al. Direct reciprocal effects of resistin and diponectin on vascular endothelial cells: a new insight into adipocytokine- endothelial cell interactions. Biochem Biophys Resommun. 2004, 314(2): 415-419
15 Lin LY, Lin CY, Su TC, et al. Angiotensin II-induced apoptosis in human endothelial cells is inhibited byadiponectin through restoration of the association between endothelial nitric oxide synthase and heat shock protein 90. FEBS Lett, 2004, 574 (13): 106-110
16 Guzik TJ, Harrison DG. Vascular NADPH oxidases as drug targets for novel antioxidant strategies. Drug Discov Today. 2006, 11(11-12): 524-533
17 Guzik TJ, Sadowski J, Guzik B, et al. Coronary artery superoxide production and noxisoform expression in human coronary artery disease. Arterioscler Thromb Vasc Biol. 2006, 26(2): 333-339
18 Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002, 277(29); 25863-25866
19 Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30 . Nat Med. 2002; 8(7): 731-737
20 Nishimura K, Setoyama T, Tsumagari H, et al. Endogenous prostaglandins E (2) and F (2(alpha)) serve as an anti- apoptotic factor against apoptosis induced by tumor necrosis factor-alpha in mouse 3T3-L1 preadipocytes. Biosci Biotechnol Biochem. 2006, 70(9): 2145-2153
21 Behre CJ, Fagerberg B, Hulten LM, et al. The reciprocal association of adipocytokines with insulin resistance and C-reactive protein in clinically healthy men. Metabolism. 2005, 54(4): 439-444
22 Yamamoto Y, Hirose H, Saito I, et al. Correlation of theadipocyte-derived protein adiponectin with insulin resistance index and serum high-density lipoprotein- cholesterol, independent of body mass index, in the Japanese population. Clin Sci (Lond). 2002, 103(2): 137-142
23 Gannage-Yared MH, Fares F, Semaan M, and et al. Circulating osteoprotegerin is correlated with lipid profile, insulin sensitivity, adiponectin and sex steroids in an ageing male population. Clin Endocrinol (Oxf). 2006, 64(6): 652-658
24 Tilg H, Moschen AR. Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol. 2006, 6(10): 772-783
25 Maeda N, Shimomura I, Kishida K, et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med. 2002, 8(7): 731-737
26 Yokota T, Meka CS, Kouro T, et al. Adiponectin, a fat cell product, influences the earliest lymphocyte precursors in bone marrow cultures by activation of the cyclooxygenase prostaglandin pathway in stromal cells. J Immunol. 2003, 171(10): 5091-5099
27 Wolf AM, Wolf D, Rumpold H, et al. Adiponectin induces the anti-inflammatory cytokines IL-10 and IL-1RA in human leukocytes. Biochem Biophys Res Commun. 2004, 323(2):630-635
28 Neumeier M, Weigert J, Schaffler A, et al. Different effects of adiponectin isoforms in human monocytic cells. J Leukoc Biol. 2006; 79(4): 803-808
29 Kim KY, Kim JK, Han SH, et al. Adiponectin is a negative regulator of NK cell cytotoxicity. J Immunol. 2006, 176(10): 5958-5964
30 Waki H, Yamauchi T, Kamon J, et al. Generation of globular fragment of adiponectin by leukocyte elastase secreted by monocytic cell line THP-1. Endo- crinology.2005, 146(2): 790- 796
31 Fasshauer M, Paschke R, Stumvoll M, et al. Adiponectin , obesity, and cardiovascular disease. Biochem.2004, 86 (11):779-784
32 Pajvani UB, Hawk ins M , Combs TP, et al. Complex distribution, not absolute amount of adiponectin, correlates with thiazolidinedione-mediated improvement in insulin sensitivity. J Bio Chem, 2004, 279 (13): 12152-12162
33 Tabara Y, Osawa H, Kawamoto R, et al. Reduced high- molecular weight adiponectin and elevated hsCRP are synergistic risk factors for metabolic syndrome in a large scale middle-aged to elderly population: the J-SHIPP study.J Clin Endocrinol Metab. 2008, 93(3):715-722
34 Verges B, Petit JM, Duillad L, et al. Adiponectin is an important determinant of apoA-I catabolism. Arterioscler Thrombo Vasc Bio l, 2006, 26 (6): 1364-1369
35 Kobayashi M, Ohno T, Kawada T, et al. Serum adiponectin concentration: it’s correlation with diabetes-related traits and quantitative trait loci analysis in mouse SMXA recombinant inbred strains. Biosci Biotechnol Biochem.2006, 70(3):677-683
36 von-EynattenM , Hamann A , TwardellaD, et al. Relationship of adiponectin with markers of systemic inflammation, atherogenic dyslipidemia, and heart failure in patients with coronary heart disease. Clin Chem. 2006, 52 (5): 853-859
37 Xu A, Yin S, Wong L, et al. Adiponectin ameliorates dyslipidemia induced by the human immunodeficiency virus protease inhibitor ritonavir in mice. Endocrinology. 2004, 145(2): 487-494
38 Kubota N, Terauchi Y, Yamauchi T, et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem. 2002; 277(29): 25863-25866
39 Yoon MJ, Lee GY, Chung JJ, et al. Adiponectin increases fatty acid oxidation in skeletal muscle cells by sequential activation of AMP-activated protein kinase, p38 mitogen-activated protein kinase, and peroxisome proliferator-activated receptor-α. Diabetes.2006, 55(9):2562-2570
40 Mori Y, Otabe S, Dina C, et al. Genome wide search for type 2 diabetes in Japanese affected sib-pairs confirms susceptibility genes on 3q, 15q, and 20q and identifies two new candidate loci on 7p and 11p. Diabetes. 2002, 51(4): 1247-1255
41 Kissebah AH, Sonnenberg GE, Myklebust J, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of metabolic syndrome. Proc Natl Acad Sci USA 2000, 97(26):14478-14483
42 Vionnet N, Hani El-H, Dupont S, et al. Genomewide search fortype 2 diabetes-susceptibility genes in French whites: evidence for a novel susceptibility locus for early-onset diabetes on chromosome 3q27-qter and independent replication of a type 2 diabetes locus on chromosome 1q21-q24. Am J Hum Genet. 2000, 67(6):1470-1480
43 Hara K, Boutin P, Mori Y, et al.Genetic variation in the gene encoding adiponectin is associated with an increased risk of type 2 diabetes in the Japanese population. Diabetes.2002, 51(2):536-540
44 Hara K, Yamauchi T, Kadowaki T.Adiponectin: an adipokine linking adipocytes and type 2 diabetes in humans. Curr Diab Rep.2005, 5(2):136-140
45 Hara K, Horikoshi M, Yamauchi T, et al. Measurement of the high-molecular weight form of adiponectin in plasma is useful for the prediction of insulin resistance and metabolic syndrome. Diabetes Care.2006, 29(6):1357-1362
46 Fisher FF, Trujillo ME, Hanif W, et al. Serum high molecular weight complex of adiponectin correlates better with glucose tolerance than total serum adiponectin in Indo-Asian males. Diabetologia. 2005, 48(6):1084-1087
47 Miura A, Kajita K, Ishizawa M, et al. Inhibitory effect of ceramide on insulin-induced protein kinase Czeta translocation in rat adipocytes. Metabolism. 2003, 52(1): 19-24
48 Matsuzawa Y, Funahashi T, Kihara S, et al. Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol. 2004, 24(1): 29-33
49 Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens, negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000, 96(5): 1723-1732
50 Matsuda M, Shimomura I, Sata M, et al. Role of adiponectin in preventing vascular stenosis. J Biol Chem. 2002, 277(40): 37487-37491
51 Okamoto Y, Kihara S, Ouchi N, et al. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation. 2002, 106(22): 2767-2770
52 Yokota T, Oritani K, Takahashi I, et al. Adiponectin, a new member of the family of soluble defense collagens,negatively regulates the growth of myelomonocytic progenitors and the functions of macrophages. Blood. 2000; 96(5):1723-1732
53 Hotta K, Funahashi T, Bodkin NL, et al. Circulation concentrations of the adipocyte protein adiponectin are decreased in parrallelv with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabe-tes 2001; 50(5):1126-1133
54 Yoshihisa O, Shinji K, Noriyuki O, et al. Adiponectin reduces atherosclerosis in apolipo-protein E-deficient mice. Circulation. 2002; 106(22):2767-2770
55 Yamachi T, Kamon J, Waki H, et al. Globular adiponectin protects ob/ob mice from diabetes and Apo E-deficient mice format herosclerosis. J Biol Chem. 2003; 278(4):2461-2468
56 Ouchi N, Kihara S, Arita Y, et al. Adipocyte-derived plasmaprotein, adiponectin, suppresses lipid accumulation and class A scavengerreceptor expression in human monocyte-derived macrophages. Circulation.2001; 103(8):1057-1063
57 Otsuka F, Sugiyama S, Kojima S, et al. Plasma adiponectin levels are associated with coronary lesion complexity in men with coronary artery disease. J Am Coll Cardiol.2006, 48(6): 1155-1162
58 Kato H, Kashiwagi H, Shiraga M, et al. Adiponectin act as an endogenous anti-thrombotic factor. Arteriosclerosis Thrombotic Vascular Biol.2006, 26 (1): 224-230
59 Shibata R, Sato K, Pimentel DR, et al. Adiponectin protects against myocardial ischemia-reperfusion injury through AMPK- and COX-2-dependent mechanisms. Nat Med. 2005, 11(10):1096-1103
60 Kojima S, Funahashi T, Sakamoto T, et al. The variation of plasma concentrations of a novel, adipocyte derived protein, adiponectin, in patients with acute myocardial infarction. Heart. 2003, 89(6):667
61 Kumada M, Kihara S, Sumitsuji S, et al. Association of hypoadiponectinemia with coronary artery disease in men. Arterioscler Thromb Vasc Biol. 2003; 23(1):85-89
62 Hotta K, Funahashi T, Arita Y, et al. Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol.2000, 20 (6): 1595-1599
63 Pischon T, Girman CJ, Hotamisligil GS, et al. Plasmaadiponectin levels and risk of myocardial infarction in men. JAMA. 2004, 291(14):1730-1737