PDF herunterladen
Thromb Haemost 2013; 110(04): 641-650
DOI: 10.1160/TH13-03-0212
Theme Issue Article
Schattauer GmbH

More than a simple storage organ: Adipose tissue as a source of adipokines involved in cardiovascular disease

Gersina Rega-Kaun
1   Department of Internal Medicine II, Medical University Vienna, Austria
2   5th Department of Internal Medicine for Diabetes and Rheumatology, Wilhelminenhospital, Vienna, Austria
,
Christoph Kaun
1   Department of Internal Medicine II, Medical University Vienna, Austria
,
Johann Wojta
1   Department of Internal Medicine II, Medical University Vienna, Austria
3   Core Facility, Medical University of Vienna, Austria
4   Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
› Institutsangaben
Weitere Informationen

Publikationsverlauf

Received: 21. März 2013

Accepted after minor revision: 19. Mai 2013

Publikationsdatum:
01. Dezember 2017 (online)

Auch verfügbar auf
    Lizenzen und Reprints

Summary

Overweight and obesity in many countries have developed into a serious health problem by themselves and by their impact on other pathologies such as insulin resistance, type 2 diabetes, hypertension, heart disease and cancer. The modulation of these diseases by adipose tissue-derived biomolecules, so-called adipokines, could be the key to differentiate between metabolically healthy and unhealthy obesity. This review will discuss the pathophysiological role of selected adipokines, primarily focusing on cardiovascular diseases. Furthermore, we will highlight possible therapeutic approaches, which target these biomolecules.

Keywords

Obesity - atherosclerosis - thrombosis
 

  • References

  • 1 Must A. et al. The disease burden associated with overweight and obesity. J Am Med Assoc 1999; 282: 1523-1529.
    CrossrefPubMedGoogle Scholar
  • 2 Pischon T. et al. General and abdominal adiposity and risk of death in Europe. N Engl J Med 2008; 359: 2105-2120.
    CrossrefPubMedGoogle Scholar
  • 3 Swinburn BA. et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet 2011; 378: 804-814.
    CrossrefPubMedGoogle Scholar
  • 4 Finkelstein EA. et al. Obesity and severe obesity forecasts through 2030. Am J Prev Med 2012; 42: 563-570.
    CrossrefPubMedGoogle Scholar
  • 5 Go AS. et al. Heart disease and stroke statistics--2013 update: a report from the American Heart Association. Circulation 2013; 127: e6-e245.
    CrossrefPubMedGoogle Scholar
  • 6 Adams TD. et al. Long-term mortality after gastric bypass surgery. N Engl J Med 2007; 357: 753-761.
    CrossrefPubMedGoogle Scholar
  • 7 Hamer M, Stamatakis E. Metabolically healthy obesity and risk of all-cause and cardiovascular disease mortality. J Clin Endocrinol Metab 2012; 97: 2482-2488.
    CrossrefPubMedGoogle Scholar
  • 8 Bluher M. Are there still healthy obese patients?. Curr Opin Endocrinol Diabetes Obes 2012; 19: 341-346.
    CrossrefPubMedGoogle Scholar
  • 9 Hauner H. Secretory factors from human adipose tissue and their functional role. Proc Nutr Soc 2005; 64: 163-169.
    CrossrefPubMedGoogle Scholar
  • 10 Bluher M. Adipose tissue dysfunction in obesity. Exp Clin Endocrinol Diabetes 2009; 117: 241-250.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 11 Skurk T. et al. Relationship between adipocyte size and adipokine expression and secretion. J Clin Endocrinol Metab 2007; 92: 1023-1033.
    CrossrefPubMedGoogle Scholar
  • 12 Arita Y. et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257: 79-83.
    CrossrefPubMedGoogle Scholar
  • 13 Bruun JM. et al. Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 2003; 285: E527-E533.
    CrossrefPubMedGoogle Scholar
  • 14 Gregoire FM. Adipocyte differentiation: from fibroblast to endocrine cell. Exp Biol Med 2001; 226: 997-1002.
    CrossrefPubMedGoogle Scholar
  • 15 Guo X, Liao K. Analysis of gene expression profile during 3T3-L1 preadipocyte differentiation. Gene 2000; 251: 45-53.
    CrossrefPubMedGoogle Scholar
  • 16 Fain JN. et al. Comparison of the release of adipokines by adipose tissue, adipose tissue matrix, and adipocytes from visceral and subcutaneous abdominal adipose tissues of obese humans. Endocrinology 2004; 145: 2273-2282.
    CrossrefPubMedGoogle Scholar
  • 17 Cinti S. et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46: 2347-2355.
    CrossrefPubMedGoogle Scholar
  • 18 Lumeng CN. et al. Obesity induces a phenotypic switch in adipose tissue macrophage polarization. J Clin Invest 2007; 117: 175-184.
    CrossrefPubMedGoogle Scholar
  • 19 Zeyda M. et al. Human adipose tissue macrophages are of an anti-inflammatory phenotype but capable of excessive pro-inflammatory mediator production. Int J Obes 2007; 31: 1420-1428.
    CrossrefPubMedGoogle Scholar
  • 20 Morris DL. et al. Adipose tissue macrophages: phenotypic plasticity and diversity in lean and obese states. Curr Opin Clin Nutr Metab Care 2011; 14: 341-346.
    CrossrefPubMedGoogle Scholar
  • 21 Harford KA. et al. Fats, inflammation and insulin resistance: insights to the role of macrophage and T-cell accumulation in adipose tissue. Proc Nutr Soc 2011; 70: 408-417.
    CrossrefPubMedGoogle Scholar
  • 22 Brownlee M. Biochemistry and molecular cell biology of diabetic complications. Nature 2001; 414: 813-820.
    CrossrefPubMedGoogle Scholar
  • 23 Dasu MR, Jialal I. Free Fatty Acids in the presence of High Glucose Amplify Monocyte Inflammation via Toll-like Receptors. Am J Physiol Endocrinol Metab 2011; 300: E145-E154.
    CrossrefPubMedGoogle Scholar
  • 24 Nguyen MT. et al. A subpopulation of macrophages infiltrates hypertrophic adipose tissue and is activated by free fatty acids via Toll-like receptors 2 and 4 and JNK-dependent pathways. J Biol Chem 2007; 282: 35279-35292.
    CrossrefPubMedGoogle Scholar
  • 25 Ye J. et al. Hypoxia is a potential risk factor for chronic inflammation and adiponectin reduction in adipose tissue of ob/ob and dietary obese mice. Am J Physiol Endocrinol Metab 2007; 293: E1118-E1128.
    CrossrefPubMedGoogle Scholar
  • 26 Klein S. et al. Absence of an effect of liposuction on insulin action and risk factors for coronary heart disease. N Engl J Med 2004; 350: 2549-2557.
    CrossrefPubMedGoogle Scholar
  • 27 Sjostrom L. Bariatric surgery and reduction in morbidity and mortality: experiences from the SOS study. Int J Obes 2008; 32 (Suppl. 07) S93-S97.
    CrossrefPubMedGoogle Scholar
  • 28 Cancello R. et al. Reduction of macrophage infiltration and chemoattractant gene expression changes in white adipose tissue of morbidly obese subjects after surgery-induced weight loss. Diabetes 2005; 54: 2277-2286.
    CrossrefPubMedGoogle Scholar
  • 29 Zhang Y. et al. Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425-432.
    CrossrefPubMedGoogle Scholar
  • 30 Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 1998; 395: 763-770.
    CrossrefPubMedGoogle Scholar
  • 31 Ramachandrappa S, Farooqi IS. Genetic approaches to understanding human obesity. J Clin Invest 2011; 121: 2080-2086.
    CrossrefPubMedGoogle Scholar
  • 32 Farooqi IS. et al. Clinical and molecular genetic spectrum of congenital deficiency of the leptin receptor. N Engl J Med 2007; 356: 237-247.
    CrossrefPubMedGoogle Scholar
  • 33 Maffei M. et al. Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1995; 1: 1155-1161.
    CrossrefPubMedGoogle Scholar
  • 34 Heymsfield SB. et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. J Am Med Assoc 1999; 282: 1568-1575.
    CrossrefPubMedGoogle Scholar
  • 35 Moon HS. et al. Efficacy of metreleptin in obese patients with type 2 diabetes: cellular and molecular pathways underlying leptin tolerance. Diabetes 2011; 60: 1647-1656.
    CrossrefPubMedGoogle Scholar
  • 36 Vatier C. et al. Therapeutic use of recombinant methionyl human leptin. Biochimie 2012; 94: 2116-2125.
    CrossrefPubMedGoogle Scholar
  • 37 Montague CT. et al. Depot-related gene expression in human subcutaneous and omental adipocytes. Diabetes 1998; 47: 1384-1391.
    CrossrefPubMedGoogle Scholar
  • 38 Guo KY. et al. Effects of obesity on the relationship of leptin mRNA expression and adipocyte size in anatomically distinct fat depots in mice. Am J Physiol Regul Integr Comp Physiol 2004; 287: R112-R119.
    CrossrefPubMedGoogle Scholar
  • 39 Lonnqvist F. et al. Leptin secretion from adipose tissue in women. Relationship to plasma levels and gene expression. J Clin Invest 1997; 99: 2398-2404.
    CrossrefPubMedGoogle Scholar
  • 40 Lofgren P. et al. Long-term prospective and controlled studies demonstrate adipose tissue hypercellularity and relative leptin deficiency in the postobese state. J Clin Endocrinol Metab 2005; 90: 6207-6213.
    CrossrefPubMedGoogle Scholar
  • 41 Wang B. et al. Hypoxia induces leptin gene expression and secretion in human preadipocytes: differential effects of hypoxia on adipokine expression by preadipocytes. J Endocrinol 2008; 198: 127-134.
    CrossrefPubMedGoogle Scholar
  • 42 Gualillo O. et al. Elevated serum leptin concentrations induced by experimental acute inflammation. Life Sci 2000; 67: 2433-2441.
    CrossrefPubMedGoogle Scholar
  • 43 Luheshi GN. et al. Leptin actions on food intake and body temperature are mediated by IL-1. Proc Natl Acad Sci USA 1999; 96: 7047-7052.
    CrossrefPubMedGoogle Scholar
  • 44 Curat CA. et al. From blood monocytes to adipose tissue-resident macrophages: induction of diapedesis by human mature adipocytes. Diabetes 2004; 53: 1285-1292.
    CrossrefPubMedGoogle Scholar
  • 45 Gruen ML. et al. Leptin requires canonical migratory signalling pathways for induction of monocyte and macrophage chemotaxis. Am J Physiol Cell Physiol 2007; 293: C1481-C1488.
    CrossrefPubMedGoogle Scholar
  • 46 Northcott JM. et al. Adipokines and the cardiovascular system: mechanisms mediating health and disease. Can J Physiol Pharmacol 2012; 90: 1029-1059.
    CrossrefPubMedGoogle Scholar
  • 47 Rosenbaum M. et al. Leptin reverses weight loss-induced changes in regional neural activity responses to visual food stimuli. J Clin Invest 2008; 118: 2583-2591.
    PubMedGoogle Scholar
  • 48 Ozcan L. et al. Endoplasmic reticulum stress plays a central role in development of leptin resistance. Cell Metab 2009; 9: 35-51.
    CrossrefPubMedGoogle Scholar
  • 49 Kashyap SR. et al. Metabolic Effects of Bariatric Surgery in Patients With Moderate Obesity and Type 2 Diabetes: Analysis of a randomized control trial comparing surgery with intensive medical treatment. Diabetes Care. 2013. Epub ahead of print.
    CrossrefGoogle Scholar
  • 50 Hu E. et al. AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 1996; 271: 10697-10703.
    CrossrefPubMedGoogle Scholar
  • 51 Maeda K. et al. cDNA cloning and expression of a novel adipose specific collagen-like factor, apM1 (AdiPose Most abundant Gene transcript 1). Biochem Biophys Res Commun 1996; 221: 286-289.
    CrossrefPubMedGoogle Scholar
  • 52 Yamauchi T. et al. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 2002; 8: 1288-1295.
    CrossrefPubMedGoogle Scholar
  • 53 Turer AT, Scherer PE. Adiponectin: mechanistic insights and clinical implications. Diabetologia 2012; 55: 2319-2326.
    CrossrefPubMedGoogle Scholar
  • 54 Matsunami T. et al. Regulation of synthesis and oxidation of fatty acids by adiponectin receptors (AdipoR1/R2) and insulin receptor substrate isoforms (IRS-1/-2) of the liver in a nonalcoholic steatohepatitis animal model. Metabolism 2011; 60: 805-814.
    CrossrefPubMedGoogle Scholar
  • 55 Halleux CM. et al. Secretion of adiponectin and regulation of apM1 gene expression in human visceral adipose tissue. Biochem Biophys Res Commun 2001; 288: 1102-1107.
    CrossrefPubMedGoogle Scholar
  • 56 Hector J. et al. TNF-alpha alters visfatin and adiponectin levels in human fat. Horm Metab Res 2007; 39: 250-255.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 57 Kubota N. et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 2002; 277: 25863-25866.
    CrossrefPubMedGoogle Scholar
  • 58 Matsuda M. et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipo-vascular axis. J Biol Chem 2002; 277: 37487-37491.
    CrossrefPubMedGoogle Scholar
  • 59 Okamoto Y. et al. An adipocyte-derived plasma protein, adiponectin, adheres to injured vascular walls. Horm Metab Res 2000; 32: 47-50.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 60 Ouchi N. et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signalling through a cAMP-dependent pathway. Circulation 2000; 102: 1296-1301.
    CrossrefPubMedGoogle Scholar
  • 61 Kumada M. et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 2004; 109: 2046-2049.
    CrossrefPubMedGoogle Scholar
  • 62 Ohashi K. et al. Adiponectin promotes macrophage polarization toward an anti-inflammatory phenotype. J Biol Chem 2010; 285: 6153-6160.
    CrossrefPubMedGoogle Scholar
  • 63 Ouchi N. et al. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expression in human monocyte-derived macrophages. Circulation 2001; 103: 1057-1063.
    CrossrefPubMedGoogle Scholar
  • 64 Pischon T. et al. Plasma adiponectin levels and risk of myocardial infarction in men. J Am Med Assoc 2004; 291: 1730-1737.
    CrossrefPubMedGoogle Scholar
  • 65 Shioji K. et al. Relationship of serum adiponectin level to adverse cardiovascular events in patients who undergo percutaneous coronary intervention. Circ J 2007; 71: 675-680.
    CrossrefPubMedGoogle Scholar
  • 66 Persson J. et al. Low plasma adiponectin concentration is associated with myocardial infarction in young individuals. J Intern Med 2010; 268: 194-205.
    CrossrefPubMedGoogle Scholar
  • 67 Sattar N. et al. Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation 2006; 114: 623-629.
    CrossrefPubMedGoogle Scholar
  • 68 Pischon T. et al. Letter by Pischon et al regarding article, "Adiponectin and coronary heart disease: a prospective study and meta-analysis". Circulation 2007; 115: e322. author reply e3.
    CrossrefPubMedGoogle Scholar
  • 69 Yamashita T. et al. Combination of serum adiponectin level and metabolic syndrome is closely associated with coronary artery disease in Japanese subjects with good glycemic control. Intern Med 2010; 49: 721-727.
    CrossrefPubMedGoogle Scholar
  • 70 Holland WL. et al. Receptor-mediated activation of ceramidase activity initiates the pleiotropic actions of adiponectin. Nat Med 2011; 17: 55-63.
    CrossrefPubMedGoogle Scholar
  • 71 Stofkova A. Leptin and adiponectin: from energy and metabolic dysbalance to inflammation and autoimmunity. Endocr Regul 2009; 43: 157-168.
    PubMedGoogle Scholar
  • 72 Kistorp C. et al. Plasma adiponectin, body mass index, and mortality in patients with chronic heart failure. Circulation 2005; 112: 1756-1762.
    CrossrefPubMedGoogle Scholar
  • 73 Matsumoto M. et al. Decrease in serum adiponectin levels in response to treatment predicts good prognosis in acute decompensated heart failure. J Clin Hypertens 2010; 12: 900-904.
    CrossrefPubMedGoogle Scholar
  • 74 Miyazaki Y, DeFronzo RA. Rosiglitazone and pioglitazone similarly improve insulin sensitivity and secretion, glucose tolerance and adipocytokines in type 2 diabetic patients. Diabetes Obes Metab 2008; 10: 1204-1211.
    CrossrefPubMedGoogle Scholar
  • 75 Iwaki M. et al. Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 2003; 52: 1655-1663.
    CrossrefPubMedGoogle Scholar
  • 76 Bodles AM. et al. Pioglitazone increases secretion of high-molecular-weight adiponectin from adipocytes. Am J Physiol Endocrinol Metab 2006; 291: E1100-E1105.
    CrossrefPubMedGoogle Scholar
  • 77 Saremi A. et al. Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors. Arterioscler Thromb Vasc Biol 2013; 33: 393-399.
    CrossrefPubMedGoogle Scholar
  • 78 Yang HB. et al. Pioglitazone induces regression and stabilization of coronary atherosclerotic plaques in patients with impaired glucose tolerance. Diabet Med 2012; 29: 359-365.
    CrossrefPubMedGoogle Scholar
  • 79 Sam S. et al. Pioglitazone-mediated changes in lipoprotein particle composition are predicted by changes in adiponectin level in type 2 diabetes. J Clin Endocrinol Metab 2012; 97: E110-E114.
    CrossrefPubMedGoogle Scholar
  • 80 Shen X. et al. Pioglitazone prevents hyperglycemia induced decrease of AdipoR1 and AdipoR2 in coronary arteries and coronary VSMCs. Mol Cell Endocrinol 2012; 363: 27-35.
    CrossrefPubMedGoogle Scholar
  • 81 Nesto RW. et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation 2003; 108: 2941-2948.
    CrossrefPubMedGoogle Scholar
  • 82 Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med 2007; 356: 2457-2471.
    CrossrefPubMedGoogle Scholar
  • 83 Dormandy JA. et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PROactive Study (PROspective pioglitAzone Clinical Trial In macroVascular Events): a randomised controlled trial. Lancet 2005; 366: 1279-1289.
    CrossrefPubMedGoogle Scholar
  • 84 Athyros VG. et al. Should adipokines be considered in the choice of the treatment of obesity-related health problems?. Curr Drug Targets 2010; 11: 122-135.
    CrossrefPubMedGoogle Scholar
  • 85 Vaiopoulos AG. et al. The role of adiponectin in human vascular physiology. Int J Cardiol 2012; 155: 188-193.
    CrossrefPubMedGoogle Scholar
  • 86 Dutheil F. et al. Blood lipids and adipokines concentrations during a 6 months nutritional and physical activity intervention for metabolic syndrome treatment. Lipids Health Dis 2010; 9: 148.
    CrossrefPubMedGoogle Scholar
  • 87 Hulver MW. et al. Adiponectin is not altered with exercise training despite enhanced insulin action. Am J Physiol Endocrinol Metab 2002; 283: E861-E865.
    CrossrefPubMedGoogle Scholar
  • 88 Butner KL. et al. A review of weight loss following Roux-en-Y gastric bypass vs restrictive bariatric surgery: impact on adiponectin and insulin. Obes Surg 2010; 20: 559-568.
    CrossrefPubMedGoogle Scholar
  • 89 Komiya T. et al. Cloning of the novel gene intelectin, which is expressed in intestinal paneth cells in mice. Biochem Biophys Res Commun 1998; 251: 759-762.
    CrossrefPubMedGoogle Scholar
  • 90 Schaffler A. et al. Genomic structure of human omentin, a new adipocytokine expressed in omental adipose tissue. Biochim Biophys Acta 2005; 1732: 96-102.
    CrossrefPubMedGoogle Scholar
  • 91 Yang RZ. et al. Identification of omentin as a novel depot-specific adipokine in human adipose tissue: possible role in modulating insulin action. Am J Physiol Endocrinol Metab 2006; 290: E1253-E1261.
    CrossrefPubMedGoogle Scholar
  • 92 de Souza Batista CM. et al. Omentin plasma levels and gene expression are decreased in obesity. Diabetes 2007; 56: 1655-1661.
    CrossrefPubMedGoogle Scholar
  • 93 Auguet T. et al. New adipokines vaspin and omentin. Circulating levels and gene expression in adipose tissue from morbidly obese women. BMC Med Genet 2011; 12: 60.
    CrossrefPubMedGoogle Scholar
  • 94 Jialal I. et al. Increased chemerin and decreased omentin-1 in both adipose tissue and plasma in nascent metabolic syndrome. J Clin Endocrinol Metab 2013; 98: E514-E517.
    CrossrefPubMedGoogle Scholar
  • 95 Liu R. et al. Omentin-1 is associated with carotid atherosclerosis in patients with metabolic syndrome. Diabetes Res Clin Pract 2011; 93: 21-25.
    CrossrefPubMedGoogle Scholar
  • 96 Moreno-Navarrete JM. et al. Circulating omentin as a novel biomarker of endothelial dysfunction. Obesity 2011; 19: 1552-1559.
    CrossrefPubMedGoogle Scholar
  • 97 Zhong X. et al. Omentin inhibits TNF-alpha-induced expression of adhesion molecules in endothelial cells via ERK/NF-kappaB pathway. Biochem Biophys Res Commun 2012; 425: 401-406.
    CrossrefPubMedGoogle Scholar
  • 98 Shang FJ. et al. Serum omentin-1 levels are inversely associated with the presence and severity of coronary artery disease in patients with metabolic syndrome. Biomarkers 2011; 16: 657-662.
    CrossrefPubMedGoogle Scholar
  • 99 Shibata R. et al. Circulating omentin is associated with coronary artery disease in men. Atherosclerosis 2011; 219: 811-814.
    CrossrefPubMedGoogle Scholar
  • 100 Yamawaki H. et al. Omentin, a novel adipocytokine inhibits TNF-induced vascular inflammation in human endothelial cells. Biochem Biophys Res Commun 2011; 408: 339-343.
    CrossrefPubMedGoogle Scholar
  • 101 Tan BK. et al. Metformin treatment may increase omentin-1 levels in women with polycystic ovary syndrome. Diabetes 2010; 59: 3023-3031.
    CrossrefPubMedGoogle Scholar
  • 102 Shaker M. et al. Effect of Treatment with Metformin on Omentin-1, Ghrelin and other Biochemical, Clinical Features in PCOS Patients. Oman Med J 2010; 25: 289-293.
    PubMedGoogle Scholar
  • 103 Esteghamati A. et al. Comparative effects of metformin and pioglitazone on omentin and leptin concentrations in patients with newly diagnosed diabetes: A randomized clinical trial. Regul Pept 2013; 182C: 1-6.
    CrossrefPubMedGoogle Scholar
  • 104 Yan P. et al. Effects of the long-acting human glucagon-like peptide-1 analog liraglutide on plasma omentin-1 levels in patients with type 2 diabetes mellitus. Diabetes Res Clin Pract 2011; 92: 368-374.
    CrossrefPubMedGoogle Scholar
  • 105 Saremi A. et al. Effects of aerobic training on serum omentin-1 and cardiometabolic risk factors in overweight and obese men. J Sports Sci 2010; 28: 993-998.
    CrossrefPubMedGoogle Scholar
  • 106 Moreno-Navarrete JM. et al. Circulating omentin concentration increases after weight loss. Nutr Metab 2010; 7: 27.
    CrossrefPubMedGoogle Scholar
  • 107 Scatena M. et al. Osteopontin: a multifunctional molecule regulating chronic inflammation and vascular disease. Arterioscler Thromb Vasc Biol 2007; 27: 2302-2309.
    CrossrefPubMedGoogle Scholar
  • 108 Matsui Y. et al. Osteopontin deficiency attenuates atherosclerosis in female apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2003; 23: 1029-1034.
    CrossrefPubMedGoogle Scholar
  • 109 Tousoulis D. et al. Serum osteoprotegerin and osteopontin levels are associated with arterial stiffness and the presence and severity of coronary artery disease. Int J Cardiol. 2012. Epub ahead of print.
    Google Scholar
  • 110 Matsui Y. et al. Role of osteopontin in cardiac fibrosis and remodelling in angiotensin II-induced cardiac hypertrophy. Hypertension 2004; 43: 1195-1201.
    CrossrefPubMedGoogle Scholar
  • 111 Takemoto M. et al. Enhanced expression of osteopontin by high glucose. Involvement of osteopontin in diabetic macroangiopathy. Ann NY Acad Sci 2000; 902: 357-363.
    CrossrefPubMedGoogle Scholar
  • 112 Kase S. et al. Increased osteopontin levels in the vitreous of patients with diabetic retinopathy. Ophthalmic Res 2007; 39: 143-147.
    CrossrefPubMedGoogle Scholar
  • 113 Nomiyama T. et al. Osteopontin mediates obesity-induced adipose tissue macrophage infiltration and insulin resistance in mice. J Clin Invest 2007; 117: 2877-2888.
    CrossrefPubMedGoogle Scholar
  • 114 Gomez-Ambrosi J. et al. Plasma osteopontin levels and expression in adipose tissue are increased in obesity. J Clin Endocrinol Metab 2007; 92: 3719-3727.
    CrossrefPubMedGoogle Scholar
  • 115 Kiefer FW. et al. Osteopontin expression in human and murine obesity: extensive local up-regulation in adipose tissue but minimal systemic alterations. Endocrinology 2008; 149: 1350-1357.
    CrossrefPubMedGoogle Scholar
  • 116 Pietilainen KH. et al. Global transcript profiles of fat in monozygotic twins discordant for BMI: pathways behind acquired obesity. PLoS Med 2008; 5: e51.
    CrossrefPubMedGoogle Scholar
  • 117 Omar B. et al. Regulation of the pro-inflammatory cytokine osteopontin by GIP in adipocytes--a role for the transcription factor NFAT and phosphodiesterase 3B. Biochem Biophys Res Commun 2012; 425: 812-817.
    CrossrefPubMedGoogle Scholar
  • 118 Ahlqvist E. et al. A link between GIP and osteopontin in adipose tissue and insulin resistance. Diabetes. 2013. Epub ahead of print.
    CrossrefGoogle Scholar
  • 119 Zeyda M. et al. Osteopontin is an activator of human adipose tissue macrophages and directly affects adipocyte function. Endocrinology 2011; 152: 2219-2227.
    CrossrefPubMedGoogle Scholar
  • 120 Schaller G. et al. Increase of osteopontin plasma concentrations after bariatric surgery independent from inflammation and insulin resistance. Obes Surg 2009; 19: 351-356.
    CrossrefPubMedGoogle Scholar
  • 121 Riedl M. et al. Plasma osteopontin increases after bariatric surgery and correlates with markers of bone turnover but not with insulin resistance. J Clin Endocrinol Metab 2008; 93: 2307-2312.
    CrossrefPubMedGoogle Scholar
  • 122 Nakamachi T. et al. PPARalpha agonists suppress osteopontin expression in macrophages and decrease plasma levels in patients with type 2 diabetes. Diabetes 2007; 56: 1662-1670.
    CrossrefPubMedGoogle Scholar
  • 123 Rychli K. et al. Pigment epithelium-derived factor (PEDF) as a therapeutic target in cardiovascular disease. Expert Opin Ther Targets 2009; 13: 1295-1302.
    CrossrefPubMedGoogle Scholar
  • 124 Famulla S. et al. Pigment epithelium-derived factor (PEDF) is one of the most abundant proteins secreted by human adipocytes and induces insulin resistance and inflammatory signalling in muscle and fat cells. Int J Obes 2011; 35: 762-772.
    CrossrefPubMedGoogle Scholar
  • 125 Nakamura K. et al. Serum levels of pigment epithelium-derived factor (PEDF) are positively associated with visceral adiposity in Japanese patients with type 2 diabetes. Diabetes Metab Res Rev 2009; 25: 52-56.
    CrossrefPubMedGoogle Scholar
  • 126 Crowe S. et al. Pigment epithelium-derived factor contributes to insulin resistance in obesity. Cell Metab 2009; 10: 40-47.
    CrossrefPubMedGoogle Scholar
  • 127 Chen C. et al. Plasma level of pigment epithelium-derived factor is independently associated with the development of the metabolic syndrome in Chinese men: a 10-year prospective study. J Clin Endocrinol Metab 2010; 95: 5074-5081.
    CrossrefPubMedGoogle Scholar
  • 128 Yang S. et al. Serum pigment epithelium-derived factor is elevated in women with polycystic ovary syndrome and correlates with insulin resistance. J Clin Endocrinol Metab 2011; 96: 831-836.
    CrossrefPubMedGoogle Scholar
  • 129 Yamagishi S. et al. Elevated serum levels of pigment epithelium-derived factor in the metabolic syndrome. J Clin Endocrinol Metab 2006; 91: 2447-2450.
    CrossrefPubMedGoogle Scholar
  • 130 Moreno-Navarrete JM. et al. Liver, but not adipose tissue PEDF gene expression is associated with insulin resistance. Int J Obes. 2013. Epub ahead of print.
    CrossrefGoogle Scholar
  • 131 Oberbach A. et al. Combined proteomic and metabolomic profiling of serum reveals association of the complement system with obesity and identifies novel markers of body fat mass changes. J Proteome Res 2011; 10: 4769-4788.
    CrossrefPubMedGoogle Scholar
  • 132 Tschoner A. et al. Effect of weight loss on serum pigment epithelium-derived factor levels. Eur J Clin Invest 2011; 41: 937-942.
    CrossrefPubMedGoogle Scholar
  • 133 Ogata N. et al. Plasma concentration of pigment epithelium-derived factor in patients with diabetic retinopathy. J Clin Endocrinol Metab 2007; 92: 1176-1179.
    CrossrefPubMedGoogle Scholar
  • 134 Chavan SS. et al. Identification of pigment epithelium-derived factor as an adipocyte-derived inflammatory factor. Mol Med 2012; 18: 1161-1168.
    CrossrefPubMedGoogle Scholar
  • 135 Tahara N. et al. Serum level of pigment epithelium-derived factor is a marker of atherosclerosis in humans. Atherosclerosis 2011; 219: 311-315.
    CrossrefPubMedGoogle Scholar
  • 136 Yamagishi S. et al. Atheroprotective properties of pigment epithelium-derived factor (PEDF) in cardiometabolic disorders. Curr Pharm Des 2009; 15: 1027-1033.
    CrossrefPubMedGoogle Scholar
  • 137 Ueda S. et al. Administration of pigment epithelium-derived factor inhibits left ventricular remodelling and improves cardiac function in rats with acute myocardial infarction. Am J Pathol 2011; 178: 591-598.
    CrossrefPubMedGoogle Scholar
  • 138 Rychli K. et al. Prognostic value of pigment epithelium-derived factor in patients with advanced heart failure. Chest 2010; 138: 656-664.
    CrossrefPubMedGoogle Scholar
  • 139 Faber DR. et al. Role of adipose tissue in haemostasis, coagulation and fibrinolysis. Obes Rev 2009; 10: 554-563.
    CrossrefPubMedGoogle Scholar
  • 140 Van De Craen B. et al. The Biochemistry, Physiology and Pathological roles of PAI-1 and the requirements for PAI-1 inhibition in vivo. Thromb Res 2012; 130: 576-585.
    CrossrefPubMedGoogle Scholar
  • 141 Kockx M. et al. Relationship between visceral fat and PAI-1 in overweight men and women before and after weight loss. Thromb Haemost 1999; 82: 1490-1496.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 142 Primrose JN. et al. Reduction in factor VII, fibrinogen and plasminogen activator inhibitor-1 activity after surgical treatment of morbid obesity. Thromb Haemost 1992; 68: 396-399.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 143 Alessi MC, Juhan-Vague I. PAI-1 and the metabolic syndrome: links, causes, and consequences. Arterioscler Thromb Vasc Biol 2006; 26: 2200-2207.
    CrossrefPubMedGoogle Scholar
  • 144 Kruszynska YT. et al. Effects of troglitazone on blood concentrations of plasminogen activator inhibitor 1 in patients with type 2 diabetes and in lean and obese normal subjects. Diabetes 2000; 49: 633-639.
    CrossrefPubMedGoogle Scholar
  • 145 Trost S. et al. Impaired fibrinolysis and risk for cardiovascular disease in the metabolic syndrome and type 2 diabetes. Curr Diab Rep 2006; 6: 47-54.
    CrossrefPubMedGoogle Scholar
  • 146 Diebold I. et al. The ’PAI-1 paradox’ in vascular remodelling. Thromb Haemost 2008; 100: 984-991.
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 147 Crandall DL. et al. Modulation of adipose tissue development by pharmacological inhibition of PAI-1. Arterioscler Thromb Vasc Biol 2006; 26: 2209-2215.
    CrossrefPubMedGoogle Scholar
  • 148 Alessi MC. et al. Plasminogen activator inhibitor-1, adipose tissue and insulin resistance. Curr Opin Lipidol 2007; 18: 240-245.
    CrossrefPubMedGoogle Scholar
  • 149 Rega G. et al. Inflammatory cytokines interleukin-6 and oncostatin m induce plasminogen activator inhibitor-1 in human adipose tissue. Circulation 2005; 111: 1938-1945.
    CrossrefPubMedGoogle Scholar
  • 150 Ekstrom M. et al. Stimulated in vivo synthesis of plasminogen activator inhibitor-1 in human adipose tissue. Thromb Haemost 2012; 108: 485-492.
    Artikel in Thieme ConnectPubMedGoogle Scholar