Brief Reviews |
From the Department of Internal Medicine and Molecular Science, Osaka University Graduate School, Sumitomo Hospital, Osaka, Japan.
Correspondence to Yuji Matsuzawa, Osaka University Graduate School, Sumitomo Hospital, 5-3-20 Nakanoshima, Kita-Ku, Osaka, 530-0005, Japan. E-mail matsuzawa-yuji{at}sumitomo-hp.or.jp
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Key Words: adiponectin adipocytokines visceral fat multiple risk factors
| Introduction |
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| Molecular Characteristic of Adipocytes |
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have been well recognized as bioactive substances from adipose tissues, which control the functions of other organs. We classified these adipose tissuederived bioactive substances as adipocytokines, although some of them are not cytokines according to the classical category.
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The genes for plasminogen activator inhibitor type 1(PAI-1) and heparin binding endothelial growth factorlike growth factor are found to be highly expressed in adipose tissue.12,13 PAI-1 mRNA levels increased up to 10 times in visceral adipose tissue during development of fat accumulation in ventromedial hypothalamic lesioned rats, which is an experimental animal model of obesity, whereas it remained unchanged in the subcutaneous adipose tissue. We also demonstrated that plasma levels of PAI-1 were significantly correlated with visceral adiposity determined by CT scan in human subjects. Circulating PAI-1 has been considered to be a strong risk factor of coronary artery disease.14 These data suggest that the secreted PAI-1 from accumulated visceral fat may contribute to the determination of plasma PAI-1 levels, and increased secretion of PAI-1 from accumulated visceral adipose tissue may have an important role in the development of thrombotic disorders and atherosclerosis frequently found in obesity, especially visceral obesity.
Discovery of Adiponectin and Its Clinical Significance
As mentioned earlier, 40% of expressed genes in adipose tissue were unknown or, in other words, novel genes. The gene that expressed most abundantly and specifically in adipose tissue was also a novel gene.15 The molecule encoded by this gene, adipose most abundant gene transcript-1, possesses a signal peptide, collagen-like motif and globular domain, and has the significant homology with collagen X and VIII and complement factor C1q (Figure 2).15 We termed this matrix-like protein adiponectin. The mouse homolog of adiponectin has been cloned as ACRP30 and AdipoQ.16,17 We established the method for the determination of plasma adiponectin levels using enzyme-linked immunosorbent assay.18 Plasma levels of adiponectin in human are substantially high, up to 5 to 10 µg/mL on average. Interestingly, plasma levels are negatively correlated with body mass index, whereas leptin, another adipose tissue-specific secretory protein, is known to increase with body mass index.19 The negative correlation is stronger between adiponectin levels and visceral adiposity than between the protein and subcutaneous adiposity. The mechanism of reduction in plasma adiponectin levels in the subjects with visceral fat accumulation is not yet clarified. We reported that TNF-
is a strong inhibitor of adiponectin promoter activity.20 The negative correlation between visceral adiposity and adiponectin levels might be explained by the increased secretion from the accumulated visceral fat as at least 1 mechanism.
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We found that diabetic patients have lower adiponectin levels than control subjects. Diabetic patients with macroangiopathy also have lower levels of adiponectin than those without macroangiopathy.21 Lindsay et al22 also demonstrated that plasma levels of adiponectin were lower in Pima Indians, a unique cohort with high prevalence of obesity, with diabetes. They also demonstrated that plasma levels of adiponectin are strongly correlated with insulin sensitivity evaluated by glucose disposal rate.23 These results suggest that adiponectin has an important role in insulin actions and hypoadiponectinemia may result in insulin resistance and diabetes mellitus. Although it has not been clarified whether hypoadiponectinemia absorbed in diabetic patients is genetic or is attributed to visceral fat accumulation, adiponectin may play a crucial role in the development of diabetes mellitus and high adiponectin levels should protect the impairment of glucose metabolism, as demonstrated in the study of Pima Indians. Recent studies have also shown that subjects with hypertension have lower levels of plasma adiponectin.24
The more important significance of adiponectin is that this protein shows lower levels in ischemic heart disease.25 Kaplan-Meyer analysis in subjects with renal insufficiency demonstrated that the subjects with hypoadiponectinemia died of cardiac events more frequently during 4 years of observation.26 These data suggest that hypoadiponectinemia might be a novel and important risk factor of atherosclerotic disease.25
Cell Biological Functions of Adiponectin
A large amount of adiponectin flows with the blood stream inside of vascular walls. It would be interesting to know whether adiponectin can enter into vascular walls. Immunohistochemical examination using anti-adiponectin antibody demonstrated that there is no existence of adiponectin in the untreated normal vascular walls in rabbit. However, markedly positive immunohistochemical stain was detected in the balloon-injured vascular walls.27 Because adiponectin has been shown to have an ability to bind subendothelial collagen, such as collagen V, VIII, and X, endothelial injury may induce the entering of adiponectin into subendothelial space by binding to these collagens.
Atherosclerotic cellular changes consist of basically the following 3 cellular phenomena: monocyte adhesion to endothelial cells by the expression of adhesion molecules, oxidized LDL uptake of macrophages through scavenger receptors, and proliferation of migrated smooth muscle cells by the action of platelet-derived growth factors or heparin-binding endothelial growth factorlike growth factor. Adiponectin has potential inhibitory activities of these atherogenic cellular phenomena. Physiological concentration of adiponectin was demonstrated to strongly inhibit the expression of adhesion molecules, including intracellular adhesion molecule-1, vascular cellular adhesion molecule-1, and E-selectin.28 Adiponectin was shown to inhibit the TNF-
induced nuclear factor-
B activation through the inhibition of I
B phosphorylation, which might be a major molecular mechanism for the inhibition of monocyte adhesion to endothelial cells.29 Adiponectin also inhibits the expression of the scavenger receptor class A-1 (SR-A) of macrophages, resulting in markedly decreased uptake of oxidized LDL and inhibition of foam cell formation.30 In addition, adiponectin inhibits the proliferation and migration of smooth muscle cells. This inhibition was shown to be attributable to the binding competition to platelet-derived growth factor-BB receptor of adiponectin and the inhibition of signal transduction through extracellular signal-related kinase (ERK).31 From these vascular cellular functions, adiponectin may have a potential antiatherogenicity. In humans, many offensive factors are present, including oxidized LDL, inflammatory stimuli, and chemical substances that may induce vascular injuries. At that time, adiponectin secreted from adipose tissues may go into the injured arteries and protect against the development of atherogenic vascular changes (Figure 3). Therefore, adiponectin might be likened firefighters who put out the fire of the vascular walls while it is still small. When the plasma levels of adiponectin are decreased in the subjects with visceral fat accumulation, the small fire may become bigger and bigger because of the shortage of firefighters.
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Genetic Hypoadiponectinemia and Atherosclerosis
To know whether primary hypoadiponectinemia causes metabolic disturbances, including insulin resistance and atherosclerotic vascular changes, we investigated the clinical profiles of the subjects with gene mutation of adiponectin, which has been recently found. In the present study, we found 4 types of missense mutation, in which I164T mutation was the most frequent and was accompanied by marked hypoadiponectinemia. So far, we have found 9 subjects with I164T mutation, 8 of 9 accompanied by hypertension or hyperlipidemia and 9 of 9 accompanied by impaired glucose metabolism, including IGT or diabetes mellitus. In addition, 6 of 9 already had coronary artery disease.32,33 These results suggest that genetic hypoadiponectinemia may be part of the genetic background of metabolic syndrome for a variety of metabolic and cardiovascular diseases.
To confirm this concept, we established the knockout (KO) mouse of adiponectin gene. The KO mice showed no specific phenotype when no high-fat or high-sucrose diet was loaded. However, high-fat and high-sucrose diet induced marked elevation of plasma glucose as well as plasma insulin levels in the KO mice. The KO mice also showed marked insulin resistance, estimated by insulin tolerance test during high-fat and high-sucrose diet. The supplementation of adiponectin by adenovirus transfection clearly improved this insulin resistance.34 Increased intimal smooth muscle cell proliferation was also observed in the injured aorta in the KO mice, which was rescued by the supplementation of adiponectin in adenovirus-transfected KO mice, suggesting that adiponectin may have an important role in the prevention against vascular remodeling during endothelial injury.35
Apolipoprotein Edeficient mice were treated with recombinant adenovirus-expressed human adiponectin. The plasma adiponectin levels in adenovirus-adiponectintreated mice increased 48 times as much as in control mice. On the fourteenth day after adenovirus-adiponectin injection, the plaque formation in aortic sinus was inhibited by 30% compared with control apolipoprotein E KO mice.36 The lesions of adiponectin-treated mice and the lipid droplets became smaller compared with nontreated mice. Immunohistochemical analyses demonstrated that the adenovirus-mediated adiponectin migrated to foam cells in the fatty streak lesions.31 The real-time quantitative polymerase chain reaction revealed that adenovirus-adiponectin treatment significantly suppressed the mRNA levels of vascular cellular adhesion molecule-1 by 29% and SR-A by 34% and tended to reduce levels of TNF-
mRNA without affecting those of CD36 in the aortic tissue. These observation confirmed that adiponectin suppresses the development of atherosclerosis.
These results together demonstrate that genetic hypoadiponectinemia can be an important background for both insulin resistance and atherosclerotic vascular disease, which may correspond to so-called metabolic syndrome.
| Conclusions |
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or PAI-1 induced by the accumulation of visceral obesity might be a major background of vascular changes as well as metabolic disorders, including insulin resistance, which are the characteristics of so-called metabolic syndrome (Figure 4).
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Received May 27, 2003; accepted August 26, 2003.
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S. H. Han, M. J. Quon, J.-a Kim, and K. K. Koh Adiponectin and Cardiovascular Disease: Response to Therapeutic Interventions J. Am. Coll. Cardiol., February 6, 2007; 49(5): 531 - 538. [Abstract] [Full Text] [PDF] |
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H. Takano, Y. Kodama, Y. Kitta, T. Nakamura, J.-e. Obata, A. Mende, K.-i. Kawabata, Y. Saitoh, D. Fujioka, T. Kobayashi, et al. Transcardiac adiponectin gradient is independently related to endothelial vasomotor function in large and resistance coronary arteries in humans Am J Physiol Heart Circ Physiol, December 1, 2006; 291(6): H2641 - H2646. [Abstract] [Full Text] [PDF] |
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F. Otsuka, S. Sugiyama, S. Kojima, H. Maruyoshi, T. Funahashi, K. Matsui, T. Sakamoto, M. Yoshimura, K. Kimura, S. Umemura, et al. Plasma Adiponectin Levels Are Associated With Coronary Lesion Complexity in Men With Coronary Artery Disease J. Am. Coll. Cardiol., September 19, 2006; 48(6): 1155 - 1162. [Abstract] [Full Text] [PDF] |
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K. Kajimoto, H. Naraba, and N. Iwai MicroRNA and 3T3-L1 pre-adipocyte differentiation RNA, September 1, 2006; 12(9): 1626 - 1632. [Abstract] [Full Text] [PDF] |
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T. O. Kiviniemi, A. Snapir, M. Saraste, J. O. Toikka, O. T. Raitakari, M. Ahotupa, J. J. Hartiala, M. Scheinin, and J. W. Koskenvuo Determinants of coronary flow velocity reserve in healthy young men Am J Physiol Heart Circ Physiol, August 1, 2006; 291(2): H564 - H569. [Abstract] [Full Text] [PDF] |
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N. Tsuboyama-Kasaoka, C. Shozawa, K. Sano, Y. Kamei, S. Kasaoka, Y. Hosokawa, and O. Ezaki Taurine (2-Aminoethanesulfonic Acid) Deficiency Creates a Vicious Circle Promoting Obesity Endocrinology, July 1, 2006; 147(7): 3276 - 3284. [Abstract] [Full Text] [PDF] |
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M. Daval, F. Foufelle, and P. Ferre Functions of AMP-activated protein kinase in adipose tissue J. Physiol., July 1, 2006; 574(1): 55 - 62. [Abstract] [Full Text] [PDF] |
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Y. Wang, K. S. L. Lam, L. Chan, K. W. Chan, J. B. B. Lam, M. C. Lam, R. C. L. Hoo, W. W. N. Mak, G. J. S. Cooper, and A. Xu Post-translational Modifications of the Four Conserved Lysine Residues within the Collagenous Domain of Adiponectin Are Required for the Formation of Its High Molecular Weight Oligomeric Complex J. Biol. Chem., June 16, 2006; 281(24): 16391 - 16400. [Abstract] [Full Text] [PDF] |
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G. Targher, L. Bertolini, R. Padovani, S. Rodella, G. Zoppini, L. Zenari, M. Cigolini, G. Falezza, and G. Arcaro Relations Between Carotid Artery Wall Thickness and Liver Histology in Subjects With Nonalcoholic Fatty Liver Disease. Diabetes Care, June 1, 2006; 29(6): 1325 - 1330. [Abstract] [Full Text] [PDF] |
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C. Langenberg, J. Bergstrom, C. Scheidt-Nave, J. Pfeilschifter, and E. Barrett-Connor Cardiovascular Death and the Metabolic Syndrome: Role of adiposity-signaling hormones and inflammatory markers. Diabetes Care, June 1, 2006; 29(6): 1363 - 1369. [Abstract] [Full Text] [PDF] |
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B. Verges, J. M. Petit, L. Duvillard, G. Dautin, E. Florentin, F. Galland, and P. Gambert Adiponectin Is an Important Determinant of ApoA-I Catabolism Arterioscler Thromb Vasc Biol, June 1, 2006; 26(6): 1364 - 1369. [Abstract] [Full Text] [PDF] |
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D. Fujioka, K.-i. Kawabata, Y. Saito, T. Kobayashi, T. Nakamura, Y. Kodama, H. Takano, J.-e. Obata, Y. Kitta, K. Umetani, et al. Role of adiponectin receptors in endothelin-induced cellular hypertrophy in cultured cardiomyocytes and their expression in infarcted heart Am J Physiol Heart Circ Physiol, June 1, 2006; 290(6): H2409 - H2416. [Abstract] [Full Text] [PDF] |
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J.-P. Despres Abdominal obesity: the most prevalent cause of the metabolic syndrome and related cardiometabolic risk Eur. Heart J. Suppl., May 1, 2006; 8(suppl_B): B4 - B12. [Abstract] [Full Text] [PDF] |
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K. Matsushita, H. Yatsuya, K. Tamakoshi, K. Wada, R. Otsuka, S. Takefuji, K. Sugiura, T. Kondo, T. Murohara, and H. Toyoshima Comparison of Circulating Adiponectin and Proinflammatory Markers Regarding Their Association With Metabolic Syndrome in Japanese Men Arterioscler Thromb Vasc Biol, April 1, 2006; 26(4): 871 - 876. [Abstract] [Full Text] [PDF] |
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M. Gary-Bobo, G. Elachouri, B. Scatton, G. Le Fur, F. Oury-Donat, and M. Bensaid The Cannabinoid CB1 Receptor Antagonist Rimonabant (SR141716) Inhibits Cell Proliferation and Increases Markers of Adipocyte Maturation in Cultured Mouse 3T3 F442A Preadipocytes Mol. Pharmacol., February 1, 2006; 69(2): 471 - 478. [Abstract] [Full Text] [PDF] |
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H. Kato, H. Kashiwagi, M. Shiraga, S. Tadokoro, T. Kamae, H. Ujiie, S. Honda, S. Miyata, Y. Ijiri, J. Yamamoto, et al. Adiponectin Acts as an Endogenous Antithrombotic Factor Arterioscler Thromb Vasc Biol, January 1, 2006; 26(1): 224 - 230. [Abstract] [Full Text] [PDF] |
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H. Ando, H. Yanagihara, Y. Hayashi, Y. Obi, S. Tsuruoka, T. Takamura, S. Kaneko, and A. Fujimura Rhythmic Messenger Ribonucleic Acid Expression of Clock Genes and Adipocytokines in Mouse Visceral Adipose Tissue Endocrinology, December 1, 2005; 146(12): 5631 - 5636. [Abstract] [Full Text] [PDF] |
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H. Koyama, T. Shoji, H. Yokoyama, K. Motoyama, K. Mori, S. Fukumoto, M. Emoto, T. Shoji, H. Tamei, H. Matsuki, et al. Plasma Level of Endogenous Secretory RAGE Is Associated With Components of the Metabolic Syndrome and Atherosclerosis Arterioscler Thromb Vasc Biol, December 1, 2005; 25(12): 2587 - 2593. [Abstract] [Full Text] [PDF] |
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J.-P. Despres, A. Golay, L. Sjostrom, and the Rimonabant in Obesity-Lipids Study Group Effects of Rimonabant on Metabolic Risk Factors in Overweight Patients with Dyslipidemia N. Engl. J. Med., November 17, 2005; 353(20): 2121 - 2134. [Abstract] [Full Text] [PDF] |
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L. L. Y. Chan, Q. Chen, A. G. G. Go, E. K. Y. Lam, and E. T. S. Li Reduced Adiposity in Bitter Melon (Momordica charantia)-Fed Rats Is Associated with Increased Lipid Oxidative Enzyme Activities and Uncoupling Protein Expression J. Nutr., November 1, 2005; 135(11): 2517 - 2523. [Abstract] [Full Text] [PDF] |
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M. Kivimaki, D. A. Lawlor, M. Juonala, G. Davey Smith, M. Elovainio, L. Keltikangas-Jarvinen, J. Vahtera, J. S.A. Viikari, and O. T. Raitakari Lifecourse Socioeconomic Position, C-Reactive Protein, and Carotid Intima-Media Thickness in Young Adults: The Cardiovascular Risk in Young Finns Study Arterioscler Thromb Vasc Biol, October 1, 2005; 25(10): 2197 - 2202. [Abstract] [Full Text] [PDF] |
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M. Yilmaz, N. Bukan, R. Ersoy, A. Karakoc, I. Yetkin, G. Ayvaz, N. Cakir, and M. Arslan Glucose intolerance, insulin resistance and cardiovascular risk factors in first degree relatives of women with polycystic ovary syndrome Hum. Reprod., September 1, 2005; 20(9): 2414 - 2420. [Abstract] [Full Text] [PDF] |
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D. Rothenbacher, H. Brenner, W. Marz, and W. Koenig Adiponectin, risk of coronary heart disease and correlations with cardiovascular risk markers Eur. Heart J., August 2, 2005; 26(16): 1640 - 1646. [Abstract] [Full Text] [PDF] |
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S. Pilz, R. Horejsi, R. Moller, G. Almer, H. Scharnagl, T. Stojakovic, R. Dimitrova, G. Weihrauch, M. Borkenstein, W. Maerz, et al. Early Atherosclerosis in Obese Juveniles Is Associated with Low Serum Levels of Adiponectin J. Clin. Endocrinol. Metab., August 1, 2005; 90(8): 4792 - 4796. [Abstract] [Full Text] [PDF] |
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J. B Ruige, D. P Ballaux, T. Funahashi, I. L Mertens, Y. Matsuzawa, and L. F Van Gaal Resting metabolic rate is an important predictor of serum adiponectin concentrations: potential implications for obesity-related disorders Am. J. Clinical Nutrition, July 1, 2005; 82(1): 21 - 25. [Abstract] [Full Text] [PDF] |
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C. M. Damcott, S. H. Ott, T. I. Pollin, L. J. Reinhart, J. Wang, J. R. O'Connell, B. D. Mitchell, and A. R. Shuldiner Genetic Variation in Adiponectin Receptor 1 and Adiponectin Receptor 2 Is Associated With Type 2 Diabetes in the Old Order Amish Diabetes, July 1, 2005; 54(7): 2245 - 2250. [Abstract] [Full Text] [PDF] |
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J. Park, H. K. Rho, K. H. Kim, S. S. Choe, Y. S. Lee, and J. B. Kim Overexpression of Glucose-6-Phosphate Dehydrogenase Is Associated with Lipid Dysregulation and Insulin Resistance in Obesity Mol. Cell. Biol., June 15, 2005; 25(12): 5146 - 5157. [Abstract] [Full Text] [PDF] |
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A. J. G. Hanley, J. B. Meigs, K. Williams, S. M. Haffner, and R. B. D'Agostino Sr. Re: "(Mis)use of Factor Analysis in the Study of Insulin Resistance Syndrome" Am. J. Epidemiol., June 15, 2005; 161(12): 1182 - 1184. [Full Text] [PDF] |
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G D Kolovou, K K Anagnostopoulou, and D V Cokkinos Pathophysiology of dyslipidaemia in the metabolic syndrome Postgrad. Med. J., June 1, 2005; 81(956): 358 - 366. [Abstract] [Full Text] [PDF] |
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G. Schillaci, M. Pirro, G. Vaudo, M. R. Mannarino, G. Savarese, G. Pucci, S. S. Franklin, and E. Mannarino Metabolic Syndrome Is Associated With Aortic Stiffness in Untreated Essential Hypertension Hypertension, June 1, 2005; 45(6): 1078 - 1082. [Abstract] [Full Text] [PDF] |
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T. Kadowaki and T. Yamauchi Adiponectin and Adiponectin Receptors Endocr. Rev., May 1, 2005; 26(3): 439 - 451. [Abstract] [Full Text] [PDF] |
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S. J. Zieman, V. Melenovsky, and D. A. Kass Mechanisms, Pathophysiology, and Therapy of Arterial Stiffness Arterioscler Thromb Vasc Biol, May 1, 2005; 25(5): 932 - 943. [Abstract] [Full Text] [PDF] |
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H. Tomiyama, Y. Koji, M. Yambe, K. Motobe, K. Shiina, Z. Gulnisa, Y. Yamamoto, and A. Yamashina Elevated C-Reactive Protein Augments Increased Arterial Stiffness in Subjects With the Metabolic Syndrome Hypertension, May 1, 2005; 45(5): 997 - 1003. [Abstract] [Full Text] [PDF] |
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N. R. Qi, J. Wang, V. Zidek, V. Landa, P. Mlejnek, L. Kazdova, M. Pravenec, and T. W. Kurtz A New Transgenic Rat Model of Hepatic Steatosis and the Metabolic Syndrome Hypertension, May 1, 2005; 45(5): 1004 - 1011. [Abstract] [Full Text] [PDF] |
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A. Xu, M. C. Lam, K. W. Chan, Y. Wang, J. Zhang, R. L. C. Hoo, J. Y. Xu, B. Chen, W.-S. Chow, A. W. K. Tso, et al. Angiopoietin-like protein 4 decreases blood glucose and improves glucose tolerance but induces hyperlipidemia and hepatic steatosis in mice PNAS, April 26, 2005; 102(17): 6086 - 6091. [Abstract] [Full Text] [PDF] |
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M.-P. Chen, J. C.-R. Tsai, F.-M. Chung, S.-S. Yang, L.-L. Hsing, S.-J. Shin, and Y.-J. Lee Hypoadiponectinemia Is Associated With Ischemic Cerebrovascular Disease Arterioscler Thromb Vasc Biol, April 1, 2005; 25(4): 821 - 826. [Abstract] [Full Text] [PDF] |
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T. You, R. Yang, M. F. Lyles, D. Gong, and B. J. Nicklas Abdominal adipose tissue cytokine gene expression: relationship to obesity and metabolic risk factors Am J Physiol Endocrinol Metab, April 1, 2005; 288(4): E741 - E747. [Abstract] [Full Text] [PDF] |
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K. Ozawa, M. Miyazaki, M. Matsuhisa, K. Takano, Y. Nakatani, M. Hatazaki, T. Tamatani, K. Yamagata, J.-i. Miyagawa, Y. Kitao, et al. The Endoplasmic Reticulum Chaperone Improves Insulin Resistance in Type 2 Diabetes Diabetes, March 1, 2005; 54(3): 657 - 663. [Abstract] [Full Text] [PDF] |
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T. W.K. Ng, G. F. Watts, M. S. Farvid, D. C. Chan, and P. H. R. Barrett Adipocytokines and VLDL Metabolism: Independent Regulatory Effects of Adiponectin, Insulin Resistance, and Fat Compartments on VLDL Apolipoprotein B-100 Kinetics? Diabetes, March 1, 2005; 54(3): 795 - 802. [Abstract] [Full Text] [PDF] |
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D. C. Chan, G. F. Watts, T. W.K. Ng, Y. Uchida, N. Sakai, S. Yamashita, and P. H. R. Barrett Adiponectin and other Adipocytokines as Predictors of Markers of Triglyceride-Rich Lipoprotein Metabolism Clin. Chem., March 1, 2005; 51(3): 578 - 585. [Abstract] [Full Text] [PDF] |
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T. I. Pollin, K. Tanner, J. R. O'Connell, S. H. Ott, C. M. Damcott, A. R. Shuldiner, J. C. McLenithan, and B. D. Mitchell Linkage of Plasma Adiponectin Levels to 3q27 Explained by Association With Variation in the APM1 Gene Diabetes, January 1, 2005; 54(1): 268 - 274. [Abstract] [Full Text] [PDF] |
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S. S. Daskalopoulou, D. P. Mikhailidis, and M. Elisaf Prevention and Treatment of the Metabolic Syndrome Angiology, November 1, 2004; 55(6): 589 - 612. [Abstract] [PDF] |
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S. S. Daskalopoulou, D. P. Mikhailidis, and M. Elisaf Prevention and Treatment of the Metabolic Syndrome Angiology, November 1, 2004; 55(6): 589 - 612. [Abstract] [PDF] |
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K. S.-L. Lam, A. Xu, K. C.-B. Tan, L.-C. Wong, S.-C. Tiu, and S. Tam Serum Adiponectin Is Reduced in Acromegaly and Normalized after Correction of Growth Hormone Excess J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5448 - 5453. [Abstract] [Full Text] [PDF] |
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S. P. Bagby Obesity-Initiated Metabolic Syndrome and the Kidney: A Recipe for Chronic Kidney Disease? J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2775 - 2791. [Full Text] [PDF] |
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Y. Guan Peroxisome Proliferator-Activated Receptor Family and Its Relationship to Renal Complications of the Metabolic Syndrome J. Am. Soc. Nephrol., November 1, 2004; 15(11): 2801 - 2815. [Abstract] [Full Text] [PDF] |
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L. B. Tanko, J. M. Bruun, P. Alexandersen, Y. Z. Bagger, B. Richelsen, C. Christiansen, and P. J. Larsen Novel Associations Between Bioavailable Estradiol and Adipokines in Elderly Women With Different Phenotypes of Obesity: Implications for Atherogenesis Circulation, October 12, 2004; 110(15): 2246 - 2252. [Abstract] [Full Text] [PDF] |
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C. Menzaghi, T. Ercolino, L. Salvemini, A. Coco, S. H. Kim, G. Fini, A. Doria, and V. Trischitta Multigenic control of serum adiponectin levels: evidence for a role of the APM1 gene and a locus on 14q13 Physiol Genomics, October 4, 2004; 19(2): 170 - 174. [Abstract] [Full Text] [PDF] |
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S. Wakabayashi and Y. Aso Adiponectin Concentrations in Sera From Patients With Type 2 Diabetes Are Negatively Associated With Sympathovagal Balance as Evaluated by Power Spectral Analysis of Heart Rate Variation Diabetes Care, October 1, 2004; 27(10): 2392 - 2397. [Abstract] [Full Text] [PDF] |
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N. Satoh, M. Naruse, T. Usui, T. Tagami, T. Suganami, K. Yamada, H. Kuzuya, A. Shimatsu, and Y. Ogawa Leptin-to-Adiponectin Ratio as a Potential Atherogenic Index in Obese Type 2 Diabetic Patients Diabetes Care, October 1, 2004; 27(10): 2488 - 2490. [Full Text] [PDF] |
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J. E. Morley and R. N. Baumgartner Cytokine-Related Aging Process J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2004; 59(9): M924 - M929. [Full Text] [PDF] |
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U. Meier and A. M. Gressner Endocrine Regulation of Energy Metabolism: Review of Pathobiochemical and Clinical Chemical Aspects of Leptin, Ghrelin, Adiponectin, and Resistin Clin. Chem., September 1, 2004; 50(9): 1511 - 1525. [Abstract] [Full Text] [PDF] |
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A. Bottner, J. Kratzsch, G. Muller, T. M. Kapellen, S. Bluher, E. Keller, M. Bluher, and W. Kiess Gender Differences of Adiponectin Levels Develop during the Progression of Puberty and Are Related to Serum Androgen Levels J. Clin. Endocrinol. Metab., August 1, 2004; 89(8): 4053 - 4061. [Abstract] [Full Text] [PDF] |
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C. Hug, J. Wang, N. S. Ahmad, J. S. Bogan, T.-S. Tsao, and H. F. Lodish T-cadherin is a receptor for hexameric and high-molecular-weight forms of Acrp30/adiponectin PNAS, July 13, 2004; 101(28): 10308 - 10313. [Abstract] [Full Text] [PDF] |
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R. Shibata, N. Ouchi, S. Kihara, K. Sato, T. Funahashi, and K. Walsh Adiponectin Stimulates Angiogenesis in Response to Tissue Ischemia through Stimulation of AMP-activated Protein Kinase Signaling J. Biol. Chem., July 2, 2004; 279(27): 28670 - 28674. [Abstract] [Full Text] [PDF] |
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B. J. Goldstein and R. Scalia Adiponectin: A Novel Adipokine Linking Adipocytes and Vascular Function J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2563 - 2568. [Abstract] [Full Text] [PDF] |
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