The role of adiposity as a determinant of an inflammatory milieu

Journal of Cardiovascular Medicine

Volumn 9, Issue 5, 2008, Pages 450-460

  Calabrò, Paolo ^a,b   Limongelli, Giuseppe ^a   Pacileo, Giuseppe ^a   Di Salvo, Giovanni ^a   Golino, Paolo ^a   Calabrò, Raffaele ^a  

^a SECOND UNIVERSITY OF NAPLES   (Italy)

^b NONE   (Italy)

Author keywords

Adipose tissue; Atherosclerosis; Cardiovascular risk; Cytokines; Inflammation; Metabolic syndrome; Obesity

Indexed keywords

ACUTE PHASE PROTEIN; ADIPOCYTOKINE; AMYLOID A PROTEIN; ANGIOTENSINOGEN; APELIN; C REACTIVE PROTEIN; CANNABINOID RECEPTOR ANTAGONIST; CYTOKINE; INTERLEUKIN 6; LEPTIN; PLASMINOGEN ACTIVATOR INHIBITOR 1; RESISTIN; TRIACYLGLYCEROL; TUMOR NECROSIS FACTOR ALPHA; UNCOUPLING PROTEIN 1; VISFATIN;

ADIPOSE TISSUE; BROWN ADIPOSE TISSUE; CYTOKINE RELEASE; DISEASE ASSOCIATION; ENDOCRINE GLAND; HUMAN; INFLAMMATORY DISEASE; MACROPHAGE; NONHUMAN; OBESITY; PATHOGENESIS; REVIEW; WHITE ADIPOSE TISSUE;

ACUTE-PHASE PROTEINS; ADIPOCYTES; ADIPOKINES; ADIPONECTIN; ADIPOSE TISSUE; CARDIOVASCULAR DISEASES; HUMANS; INFLAMMATION; INFLAMMATION MEDIATORS; LEPTIN; OBESITY; RESISTIN;

EID: 42049112998     PISSN: 15582027     EISSN: None     Source Type: Journal    
DOI: 10.2459/JCM.0b013e3282eee9a8     Document Type: Review

References (126)

1. Eckel RH, Krauss RM. American Heart Association call to action: obesity as a major risk factor for coronary heart disease. AHA Nutrition Committee. Circulation 1998; 97:2099-2100.
2. Grundy SM. Obesity, metabolic syndrome, and coronary atherosclerosis. Circulation 2002; 105:2696-2698.
3. Sowers JR. Obesity as a cardiovascular risk factor. Am J Med 2003; 115 (Suppl 8A):37S-41S.
4. Sharma AM. Adipose tissue: a mediator of cardiovascular risk. Int J Obes Relat Metab Disord 2002; 26 (Suppl 4):S5-S7.
5. Engeli S, Sharma AM. Role of adipose tissue for cardiovascular-renal regulation in health and disease. Horm Metab Res 2000; 32:485-499.
6. Guerre-Millo M. Adipose tissue and adipokines: for better or worse. Diabetes Metab 2004; 30:13-19.
7. Poirier P, Eckel RH. Obesity and cardiovascular disease. Curr Atheroscler Rep 2002; 4:448-453.
8. Peelman F, Waelput W, Iserentant H, Lavens D, Eyckerman S, Zabeau L, et al. Leptin: linking adipocyte metabolism with cardiovascular and autoimmune diseases. Prog Lipid Res 2004; 43:283-301.
9. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, et al. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 1999; 100:2473-2476.
10. Shuldiner AR, Yang R, Gong DW. Resistin, obesity and insulin resistance - the emerging role of the adipocyte as an endocrine organ. N Engl J Med 2001; 345:1345-1346.
11. Bullo-Bonet M, Garcia-Lorda P, Lopez-Soriano FJ, Argiles JM, Salas-Salvado J. Tumour necrosis factor, a key role in obesity? FEBS Lett 1999; 451:215-219.
12. Yudkin JS, Kumari M, Humphries SE, Mohamed-Ali V. Inflammation, obesity, stress and coronary heart disease: is interleukin-6 the link? Atherosclerosis 2000; 148:209-214.
13. Cinti S. The adipose organ: morphological perspectives of adipose tissues. Proc Nutr Soc 2001; 60:319-328.
14. Cannon B, Nedergaard J. Brown adipose tissue: function and physiological significance. Physiol Rev 2004; 84:277-359.
15. Gavrilova O, Marcus-Samuels B, Graham D, Kim JK, Shulman GI, Castle AL, et al. Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice. J Clin Invest 2000; 105:271-278.
16. Shimomura I, Hammer RE, Ikemoto S, Brown MS, Goldstein JL. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 1999; 401:73-76.
17. Engstrom G, Stavenow L, Hedblad B, Lind P, Eriksson KF, Janzon L, et al. Inflammation-sensitive plasma proteins, diabetes, and mortality and incidence of myocardial infarction and stroke: a population-based study. Diabetes 2003; 52:442-447.
18. Festa A, D'Agostino R Jr, Williams K, Karter AJ, Mayer-Davis EJ, Tracy RP, et al. The relation of body fat mass and distribution to markers of chronic inflammation. Int J Obes Relat Metab Disord 2001; 25:1407-1415.
19. Yudkin JS, Stehouwer CD, Emeis JJ, Coppack SW. C-reactive protein in healthy subjects: associations with obesity, insulin resistance, and endothelial dysfunction: a potential role for cytokines originating from adipose tissue? Arterioscler Thromb Vasc Biol 1999; 19:972-978.
20. Bullo M, Garcia-Lorda P, Megias I, Salas-Salvado J. Systemic inflammation, adipose tissue tumor necrosis factor, and leptin expression. Obes Res 2003; 11:525-531.
21. Das UN. Is obesity an inflammatory condition? Nutrition 2001; 17:953-966.
22. Calabro P, Willerson JT, Yeh ET. Inflammatory cytokines stimulated C-reactive protein production by human coronary artery smooth muscle cells. Circulation 2003; 108:1930-1932.
23. Yudkin JS. Adipose tissue, insulin action and vascular disease: inflammatory signals. Int J Obes Relat Metab Disord 2003; 27 (Suppl 3):S25-S28.
24. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003; 112:1796-1808.
25. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, et al. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 2003; 112:1821-1830.
26. Calabro P, Chang DW, Willerson JT, Yeh ET. Release of C-reactive protein in response to inflammatory cytokines by human adipocytes: linking obesity to vascular inflammation. J Am Coll Cardiol 2005; 46:1112-1113.
27. Calabro P, Chang DW, Willerson JT, Yeh ET. Production of C-reactive protein and serum amyloid A in response to inflammatory cytokines by human adipocytes [abstract]. Eur Heart J 2005; 26 (Suppl):334-335.
28. Cousin B, Munoz O, Andre M, Fontanilles AM, Dani C, Cousin JL, et al. A role for preadipocytes as macrophage-like cells. FASEB J 1999; 13:305-312.
29. Ahima RS, Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab 2000; 11:327-332.
30. Samad F, Loskutoff DJ. Tissue distribution and regulation of plasminogen activator inhibitor-1 in obese mice. Mol Med 1996; 2:568-582.
31. Samad F, Yamamoto K, Pandey M, Loskutoff DJ. Elevated expression of transforming growth factor-β in adipose tissue from obese mice. Mol Med 1997; 3:37-48.
32. Zhang B, Graziano MP, Doebber TW, Leibowitz MD, White-Carrington S, Szalkowski DM, et al. Down-regulation of the expression of the obese gene by an antidiabetic thiazolidinedione in Zucker diabetic fatty rats and db/db mice. J Biol Chem 1996; 271:9455-9459.
33. Eriksson P, Van Harmelen V, Hoffstedt J, Lundquist P, Vidal H, Stemme V, et al. Regional variation in plasminogen activator inhibitor-1 expression in adipose tissue from obese individuals. Thromb Haemost 2000; 83:545-548.
34. Fried SK, Bunkin DA, Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 1998; 83:847-850.
35. Giacchetti G, Faloia E, Mariniello B, Sardu C, Gatti C, Camilloni MA, et al. Overexpression of the renin-angiotensin system in human visceral adipose tissue in normal and overweight subjects. Am J Hypertens 2002; 15:381-388.
36. Dandona P, Weinstock R, Thusu K, Abdel-Rahman E, Aljada A, Wadden T. Tumor necrosis factor-α in sera of obese patients: fall with weight loss. J Clin Endocrinol Metab 1998; 83:2907-2910.
37. Itoh K, Imai K, Masuda T, Abe S, Tanaka M, Koga R, et al. Relationship between changes in serum leptin levels and blood pressure after weight loss. Hypertens Res 2002; 25:881-886.
38. Ziccardi P, Nappo F, Giugliano G, Esposito K, Marfella R, Cioffi M, et al. Reduction of inflammatory cytokine concentrations and improvement of endothelial functions in obese women after weight loss over one year. Circulation 2002; 105:804-809.
39. De Pergola G, Pannacciulli N. Coagulation and fibrinolysis abnormalities in obesity. J Endocrinol Invest 2002; 25:899-904.
40. Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor-α: direct role in obesity-linked insulin resistance. Science 1993; 259:87-91.
41. Perreault M, Marette A. Targeted disruption of inducible nitric oxide synthase protects against obesity-linked insulin resistance in muscle. Nat Med 2001; 7:1138-1143.
42. Samad F, Pandey M, Loskutoff DJ. Tissue factor gene expression in the adipose tissues of obese mice. Proc Natl Acad Sci U S A 1998; 95:7591-7596.
43. Sartipy P, Loskutoff DJ. Monocyte chemoattractant protein 1 in obesity and insulin resistance. Proc Natl Acad Sci U S A 2003; 100:7265-7270.
44. Vgontzas AN, Papanicolaou DA, Bixler EO, Kales A, Tyson K, Chrousos GP. Elevation of plasma cytokines in disorders of excessive daytime sleepiness: role of sleep disturbance and obesity. J Clin Endocrinol Metab 1997; 82:1313-1316.
45. Visser M, Bouter LM, McQuillan GM, Wener MH, Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA 1999; 282:2131-2135.
46. Weyer C, Yudkin JS, Stehouwer CD, Schalkwijk CG, Pratley RE, Tataranni PA. Humoral markers of inflammation and endothelial dysfunction in relation to adiposity and in vivo insulin action in Pima Indians. Atherosclerosis 2002; 161:233-242.
47. Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, et al. Adipocyte death defines macrophage localization and function in adipose tissue of obese mice and humans. J Lipid Res 2005; 46:2347-2355.
48. Halaas JL, Gajiwala KS, Maffei M, Cohen SL, Chait BT, Rabinowitz D, et al. Weight-reducing effects of the plasma protein encoded by the obese gene. Science 1995; 269:543-546.
49. Lee GH, Proenca R, Montez JM, Carroll KM, Darvishzadeh JG, Lee JI, et al. Abnormal splicing of the leptin receptor in diabetic mice. Nature 1996; 379:632-635.
50. Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, 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.
51. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, et al. Effects of the obese gene product on body weight regulation in ob/ob mice. Science 1995; 269:540-543.
52. Clement K, Vaisse C, Lahlou N, Cabrol S, Pelloux V, Cassuto D, et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998; 392:398-401.
53. Farooqi IS, Keogh JM, Kamath S, Jones S, Gibson WT, Trussell R, et al. Partial leptin deficiency and human adiposity. Nature 2001; 414:34-35.
54. Montague CT, Farooqi IS, Whitehead JP, Soos MA, Rau H, Wareham NJ, et al. Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 1997; 387:903-908.
55. Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, et al. Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 2002; 110:1093-1103.
56. Considine RV, Sinha MK, Heiman ML, Kriauciunas A, Stephens TW, Nyce MR, et al. Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 1996; 334:292-295.
57. Oral EA, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P, et al. Leptin-replacement therapy for lipodystrophy. N Engl J Med 2002; 346:570-578.
58. Luo JD, Zhang GS, Chen MS. Leptin and cardiovascular diseases. Timely Top Med Cardiovasc Dis 2005; 9:E34.
59. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, et al. The hormone resistin links obesity to diabetes. Nature 2001; 409:307-312.
60. McTernan CL, McTernan PG, Harte AL, Levick PL, Barnett AH, Kumar S. Resistin, central obesity, and type 2 diabetes. Lancet 2002; 359:46-47.
61. Degawa-Yamauchi M, Bovenkerk JE, Juliar BE, Watson W, Kerr K, Jones R, et al. Serum resistin (FIZZ3) protein is increased in obese humans. J Clin Endocrinol Metab 2003; 88:5452-5455.
62. Kim KH, Lee K, Moon YS, Sul HS. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 2001; 276:11252-11256.
63. Patel L, Buckels AC, Kinghorn IJ, Murdock PR, Holbrook JD, Plumpton C, et al. Resistin is expressed in human macrophages and directly regulated by PPARγ activators. Biochem Biophys Res Commun 2003; 300:472-476.
64. Savage DB, Sewter CP, Klenk ES, Segal DG, Vidal-Puig A, Considine RV, et al. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-γ action in humans. Diabetes 2001; 50:2199-2202.
65. Yang RZ, Huang Q, Xu A, McLenithan JC, Eisen JA, Shuldiner AR, et al. Comparative studies of resistin expression and phylogenomics in human and mouse. Biochem Biophys Res Commun 2003; 310:927-935.
66. Calabro P, Cirillo P, Maddaloni V, Limongelli G, Weisz S, Rucco MA, et al. Adipokine resistin induces expression of adhesion molecules and tissue factor in human coronary artery endothelial cells [abstract]. Circulation 2006; 114 (Suppl):II-308.
67. Calabro P, Samudio I, Willerson JT, Yeh ET. Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. Circulation 2004; 110:3335-3340.
68. Burnett MS, Lee CW, Kinnaird TD, Stabile E, Durrani S, Dullum MK, et al. The potential role of resistin in atherogenesis. Atherosclerosis 2005; 182:241-248.
69. Adeghate E. An update on the biology and physiology of resistin. Cell Mol Life Sci 2004; 61:2485-2496.
70. Nagaev I, Smith U. Insulin resistance and type 2 diabetes are not related to resistin expression in human fat cells or skeletal muscle. Biochem Biophys Res Commun 2001; 285:561-564.
71. Fain JN, Cheema PS, Bahouth SW, Lloyd Hiler M. Resistin release by human adipose tissue explants in primary culture. Biochem Biophys Res Commun 2003; 300:674-678.
72. Lee JH, Bullen JW Jr, Stoyneva VL, Mantzoros CS. Circulating resistin in lean, obese, and insulin-resistant mouse models: lack of association with insulinemia and glycemia. Am J Physiol Endocrinol Metab 2005; 288:E625-E632.
73. Rajala MW, Qi Y, Patel HR, Takahashi N, Banerjee R, Pajvani UB, et al. Regulation of resistin expression and circulating levels in obesity, diabetes, and fasting. Diabetes 2004; 53:1671-1679.
74. Asensio C, Cettour-Rose P, Theander-Carrillo C, Rohner-Jeanrenaud F, Muzzin P. Changes in glycemia by leptin administration or high-fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis. Endocrinology 2004; 145:2206-2213.
75. Schaffler A, Buchler C, Muller-Ladner U, Herfarth H, Ehling A, Paul G, et al. Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus. Horm Metab Res 2004; 36:702-707.
76. Vendrell J, Broch M, Vilarrasa N, Molina A, Gomez JM, Gutierrez C, et al. Resistin, adiponectin, ghrelin, leptin, and proinflammatory cytokines: relationships in obesity. Obes Res 2004; 12:962-971.
77. Azuma K, Katsukawa F, Oguchi S, Murata M, Yamazaki H, Shimada A, et al. Correlation between serum resistin level and adiposity in obese individuals. Obes Res 2003; 11:997-1001.
78. Yannakoulia M, Yiannakouris N, Bluher S, Matalas AL, Klimis-Zacas D, Mantzoros CS. Body fat mass and macronutrient intake in relation to circulating soluble leptin receptor, free leptin index, adiponectin, and resistin concentrations in healthy humans. J Clin Endocrinol Metab 2003; 88:1730-1736.
79. McTernan PG, Fisher FM, Valsamakis G, Chetty R, Harte A, McTernan CL, et al. Resistin and type 2 diabetes: regulation of resistin expression by insulin and rosiglitazone and the effects of recombinant resistin on lipid and glucose metabolism in human differentiated adipocytes. J Clin Endocrinol Metab 2003; 88:6098-6106.
80. Zhang J, Qin Y, Zheng X, Qiu J, Gong L, Mao H, et al. The relationship between human serum resistin level and body fat content, plasma glucose as well as blood pressure. Zhonghua Yi Xue Za Zhi 2002; 82:1609-1612.
81. McTernan PG, McTernan CL, Chetty R, Jenner K, Fisher FM, Lauer MN, et al. Increased resistin gene and protein expression in human abdominal adipose tissue. J Clin Endocrinol Metab 2002; 87:2407.
82. Valsamakis G, McTernan PG, Chetty R, Al Daghri N, Field A, Hanif W, et al. Modest weight loss and reduction in waist circumference after medical treatment are associated with favorable changes in serum adipocytokines. Metabolism 2004; 53:430-434.
83. Heilbronn LK, Rood J, Janderova L, Albu JB, Kelley DE, Ravussin E, et al. Relationship between serum resistin concentrations and insulin resistance in nonobese, obese, and obese diabetic subjects. J Clin Endocrinol Metab 2004; 89:1844-1848.
84. Patel SD, Rajala MW, Rossetti L, Scherer PE, Shapiro L. Disulfide-dependent multimeric assembly of resistin family hormones. Science 2004; 304:1154-1158.
85. Fruebis J, Tsao TS, Javorschi S, Ebbets-Reed D, Erickson MR, Yen FT, et al. Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci U S A 2001; 98:2005-2010.
86. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 1995; 270:26746-26749.
87. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001; 7:941-946.
88. Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, et al. Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 1999; 257:79-83.
89. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA 2004; 291:1730-1737.
90. Hara K, Boutin P, Mori Y, Tobe K, Dina C, Yasuda K, 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; 51:536-540.
91. Kondo H, Shimomura I, Matsukawa Y, Kumada M, Takahashi M, Matsuda M, et al. Association of adiponectin mutation with type 2 diabetes: a candidate gene for the insulin resistance syndrome. Diabetes 2002; 51:2325-2328.
92. Takahashi M, Arita Y, Yamagata K, Matsukawa Y, Okutomi K, Horie M, et al. Genomic structure and mutations in adipose-specific gene, adiponectin. Int J Obes Relat Metab Disord 2000; 24:861-868.
93. Kissebah AH, Sonnenberg GE, Myklebust J, Goldstein M, Broman K, James RG, et al. Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome. Proc Natl Acad Sci U S A 2000; 97:14478-14483.
94. Lindsay RS, Funahashi T, Hanson RL, Matsuzawa Y, Tanaka S, Tataranni PA, et al. Adiponectin and development of type 2 diabetes in the Pima Indian population. Lancet 2002; 360:57-58.
95. Zoccali C, Mallamaci F, Tripepi G, Benedetto FA, Cutrupi S, Parlongo S, et al. Adiponectin, metabolic risk factors, and cardiovascular events among patients with end-stage renal disease. J Am Soc Nephrol 2002; 13:134-141.
96. Hotta K, Funahashi T, Bodkin NL, Ortmeyer HK, Arita Y, Hansen BC, et al. Circulating concentrations of the adipocyte protein adiponectin are decreased in parallel with reduced insulin sensitivity during the progression to type 2 diabetes in rhesus monkeys. Diabetes 2001; 50:1126-1133.
97. Ouchi N, Kihara S, Arita Y, Nishida M, Matsuyama A, Okamoto Y, 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.
98. Kumada M, Kihara S, Ouchi N, Kobayashi H, Okamoto Y, Ohashi K, et al. Adiponectin specifically increased tissue inhibitor of metalloproteinase-1 through interleukin-10 expression in human macrophages. Circulation 2004; 109:2046-2049.
99. Chen H, Montagnani M, Funahashi T, Shimomura I, Quon MJ. Adiponectin stimulates production of nitric oxide in vascular endothelial cells. J Biol Chem 2003; 278:45021-45026.
100. Kawanami D, Maemura K, Takeda N, Harada T, Nojiri T, Imai Y, et al. Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun 2004; 314:415-419.
101. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, et al. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-κB signaling through a cAMP-dependent pathway. Circulation 2000; 102:1296-1301.
102. Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, et al. Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 2003; 301:1045-1050.
103. Brekke HK, Lenner RA, Taskinen MR, Mansson JE, Funahashi T, Matsuzawa Y, et al. Lifestyle modification improves risk factors in type 2 diabetes relatives. Diabetes Res Clin Pract 2005; 68:18-28.
104. Koh KK, Quon MJ, Han SH, Chung WJ, Ahn JY, Seo YH, et al. Additive beneficial effects of losartan combined with simvastatin in the treatment of hypercholesterolemic, hypertensive patients. Circulation 2004; 110:3687-3692.
105. Koh KK, Han SH, Quon MJ, Yeal Ahn J, Shin EK. Beneficial effects of fenofibrate to improve endothelial dysfunction and raise adiponectin levels in patients with primary hypertriglyceridemia. Diabetes Care 2005; 28:1419-1424.
106. Tatemoto K, Hosoya M, Habata Y, Fujii R, Kakegawa T, Zou MX, et al. Isolation and characterization of a novel endogenous peptide ligand for the human APJ receptor. Biochem Biophys Res Commun 1998; 251:471-476.
107. Boucher J, Masri B, Daviaud D, Gesta S, Guigne C, Mazzucotelli A, et al. Apelin, a newly identified adipokine up-regulated by insulin and obesity. Endocrinology 2005; 146:1764-1771.
108. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K, et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 2005; 307:426-430.
109. Hirai K, Hussey HJ, Barber MD, Price SA, Tisdale MJ. Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Res 1998; 58:2359-2365.
110. Todorov PT, McDevitt TM, Meyer DJ, Ueyama H, Ohkubo I, Tisdale MJ. Purification and characterization of a tumor lipid-mobilizing factor. Cancer Res 1998; 58:2353-2358.
111. Russell ST, Hirai K, Tisdale MJ. Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor. Br J Cancer 2002; 86:424-428.
112. Bao Y, Yamano Y, Morishima I. A novel lebocin-like gene from erisilkworm, Samia cynthia ricini, that does not encode the antibacterial peptide lebocin. Comp Biochem Physiol B Biochem Mol Biol 2005; 140:127-131.
113. Bing C, Bao Y, Jenkins J, Sanders P, Manieri M, Cinti S, et al. Zinc-α2-glycoprotein, a lipid mobilizing factor, is expressed in adipocytes and is up-regulated in mice with cancer cachexia. Proc Natl Acad Sci U S A 2004; 101:2500-2505.
114. Ridker PM, Koenig W, Fuster V. C-reactive protein and coronary heart disease. N Engl J Med 2004; 351:295-298.
115. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, et al. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 2003; 289:1799-1804.
116. Esposito K, Marfella R, Ciotola M, Di Palo C, Giugliano F, Giugliano G, et al. Effect of a Mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial. JAMA 2004; 292:1440-1446.
117. Obisesan TO, Leeuwenburgh C, Phillips T, Ferrell RE, Phares DA, Prior SJ, et al. C-reactive protein genotypes affect baseline, but not exercise training-induced changes, in C-reactive protein levels. Arterioscler Thromb Vasc Biol 2004; 24:1874-1879.
118. Okita K, Nishijima H, Murakami T, Nagai T, Morita N, Yonezawa K, et al. Can exercise training with weight loss lower serum C-reactive protein levels? Arterioscler Thromb Vasc Biol 2004; 24:1868-1873.
119. Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, et al. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 2003; 107:671-674.
120. Erren M, Reinecke H, Junker R, Fobker M, Schulte H, Schurek JO, et al. Systemic inflammatory parameters in patients with atherosclerosis of the coronary and peripheral arteries. Arterioscler Thromb Vasc Biol 1999; 19:2355-2363.
121. Fyfe AI, Rothenberg LS, DeBeer FC, Cantor RM, Rotter JI, Lusis AJ. Association between serum amyloid A proteins and coronary artery disease: evidence from two distinct arteriosclerotic processes. Circulation 1997; 96:2914-2919.
122. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med 2000; 342:836-843.
123. Ridker PM, Rifai N, Pfeffer MA, Sacks FM, Moye LA, Goldman S, et al. Inflammation, pravastatin, and the risk of coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events (CARE) Investigators. Circulation 1998; 98:839-844.
124. Spiegelman BM. PPAR-γ: adipogenic regulator and thiazolidinedione receptor. Diabetes 1998; 47:507-514.
125. Tiikkainen M, Hakkinen AM, Korsheninnikova E, Nyman T, Makimattila S, Yki-Jarvinen H. Effects of rosiglitazone and metformin on liver fat content, hepatic insulin resistance, insulin clearance, and gene expression in adipose tissue in patients with type 2 diabetes. Diabetes 2004; 53:2169-2176.
126. Pagotto U, Pasquali R. Fighting obesity and associated risk factors by antagonising cannabinoid type 1 receptors. Lancet 2005; 365:1363-1364.