Adipokines: Molecular links between obesity and atheroslcerosis

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 288, Issue 5 57-5, 2005, Pages

  Lau, David C W ^a,b   Dhillon, Bikramjit ^a,b   Yan, Hongyun ^a,b   Szmitko, Paul E ^d   Verma, Subodh ^b,c,e  

^a UNIVERSITY OF CALGARY   (Canada)

^b UNIVERSITY OF CALGARY   (Canada)

^c ST MICHAEL'S HOSPITAL   (Canada)

^d UNIVERSITY OF TORONTO   (Canada)

^e TORONTO GENERAL HOSPITAL   (Canada)

Author keywords

Adipose tissue; Endothelium; Metabolic syndrome

Indexed keywords

ADIPONECTIN; ANGIOTENSINOGEN; C REACTIVE PROTEIN; I KAPPA B; INTERCELLULAR ADHESION MOLECULE 1; INTERLEUKIN 6; LEPTIN; PLASMINOGEN ACTIVATOR INHIBITOR 1; RESISTIN; SERUM AMYLOID A; TUMOR NECROSIS FACTOR ALPHA; VASCULAR CELL ADHESION MOLECULE 1;

ADIPOSE TISSUE; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ATHEROGENESIS; ATHEROSCLEROSIS; BLOOD CLOTTING; CARDIOVASCULAR RISK; CONTROLLED STUDY; DIABETES MELLITUS; ENDOTHELIUM INJURY; EPIDEMIC; FIBRINOLYSIS; HOMEOSTASIS; HUMAN; IMMUNOHISTOLOGY; INFLAMMATION; INSULIN RESISTANCE; METABOLIC SYNDROME X; MOUSE; NONHUMAN; OBESITY; PRIORITY JOURNAL; RAT; REVIEW;

ADIPOSE TISSUE; ANIMALS; CORONARY ARTERIOSCLEROSIS; CYTOKINES; HUMANS; OBESITY; PEPTIDE HORMONES;

EID: 18044366410     PISSN: 03636135     EISSN: None     Source Type: Journal    
DOI: 10.1152/ajpheart.01058.2004     Document Type: Review

References (127)

1. Abdel-Hafez M, Yan H, Kermouni A, and Lau DC. Adipose tissue-derived cytokines modulate preadipocyte differentiation and leptin production. Int J Obes Relat Metab Disord 26: S66, 2002 (Abstract).
2. Ahima R and Flier JS. Adipose tissue as an endocrine organ. Trends Endocrinol Metab 11: 327-332, 2000.
3. Artwohl M, Roden M, Holzenbein T, Freudenthaler A, Waldhausl W, and Baumgartner-Parzer SM. Modulation by leptin of proliferation and apoptosis in vascular endothelial cells. Int J Obes Relat Metab Disord 26: 577-580, 2002.
4. Bastard JP, Jardel C, Delattre J, Hainque B, Bruckert E, and Oberlin F. Evidence for a link between adipose tissue interleukin-6 content and serum C-reactive protein concentrations in obese subjects. Circulation 99: 2221-2222, 1999.
5. Bhagar K and Vallance P. Inflammatory cytokines impairs endothelium-dependent dilatation in human veins in vivo. Circulation 96: 3042-3047, 1997.
6. Bouloumie A, Drexler HC, Lafontan M, and Busse R. Leptin, the product of Ob gene, promotes angiogenesis. Circ Res 83: 1059-1066, 1998.
7. Bouloumie A, Marumo T, Lafontan M, and Busse R. Leptin induces oxidative stress in human endothelial cells. FASEB J 13: 1231-1238, 1999.
8. Braunwald E. Shattuck lecture-cardiovascular medicine at the turn of the millennium: triumphs, concerns, and opportunities. N Engl J Med 337: 1360-1369, 1997.
9. Brownlee M. Biochemistry and molecular biology of diabetic complications. Nat Med 414: 813-820, 2001.
10. Bruun JM, Verdich C, Toubro S, Astrup A, and Richelsen B. Association between measures of insulin sensitivity and circulating levels of interleukin-8, interleukin-6 and tumor necrosis factor-alpha. Effect of weight loss in obese men. Eur J Endocrinol 148: 535-542, 2003.
11. Burcelin R, Kamohara S, Li J, Tannenbaum GS, Charron MJ, and Friedman JM. Acute intravenous leptin infusion increases glucose turnover but not skeletal muscle glucose uptake in ob/ob mice. Diabetes 48: 1264-1269, 1999.
12. Calabro P, Samudio I, Willerson JT, and Yeh ET. Resistin promotes smooth muscle cell proliferation through activation of extracellular signal-regulated kinase 1/2 and phosphatidylinositol 3-kinase pathways. Circulation 110: 3335-3340, 2004.
13. Celerier J, Cruz A, Lamande N, Gasc JM, and Corvol P. Angiotensinogen and its cleaved derivatives inhibit angiogenesis. Hypertension 39: 224-228, 2002.
14. Cho E, Manson JE, Stampfer MJ, Solomon CG, Colditz GA, Speizer FE, Willett WC, and Hu FB. A prospective study of obesity and risk of coronary heart disease among, diabetic women. Diabetes Care 25: 1142-1148, 2002.
15. Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, and Roccella EJ; National Heart, Lung, and Blood Institute Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure; National High Blood Pressure Education Program Coordinating Committee. The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report. JAMA 289: 2560-2572, 2003.
16. Choy JC, Granville DJ, Hunt DW, and McManus BM. Endothelial cell apoptosis: biochemical characteristics and potential implications for atherosclerosis. J Mol Cell Cardiol 33: 1673-1690, 2001.
17. Christiansen T, Richelsen B, and Bruun JM. Monocyte chemoattractant protein-1 is produced in isolated adipocytes, associated with adiposity and reduced after weight loss in morbid obese subjects. Int J Obes Relat Metab Disord 29: 146-150, 2005.
18. Cooke JP and Oka RK. Does leptin cause vascular disease? Circulation 106: 1904-1905, 2002.
19. Devaraj S, Xu DY, and Jialal I. C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis. Circulation 107: 398-404, 2003.
20. Eckel RH. Obesity and heart disease: a statement for healthcare professionals from the Nutrition Committee, American Heart Association. Circulation 96: 3248-3250, 1997.
21. Emanueli C and Madeddu P. Renin-angiotensin and kallikrein-kinin systems coordinately modulate angiogenesis. Hypertension 39: e29, 2002.
22. Esposito K, Pontillo A, Di Palo C, Giugliano G, Masella M, Marfella R, and Giugliano D. Effect of weight loss and lifestyle changes on vascular inflammatory markers in obese women: a randomized trial. JAMA 289: 1799-1804, 2003.
23. Expert Panel on Detection E 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 285: 2486-2497, 2001.
24. Feingold KR, Doerrler W, Dinarello CA, Fiers W, and Grunfeld C. Stimulation of lipolysis in cultured fat cells by tumor necrosis factor, interleukin-1, and the interferons is blocked by inhibition of prostaglandin synthesis. Endocrinology 130: 10-16, 1992.
25. Ferroni P, Basili S, Falco A, and Davi G. Inflammation, insulin resistance, and obesity. Curr Atheroscler Rep 6: 424-431, 2004.
26. Festa A, D'Agostino R Jr, Tracy RP, and Haffner SM; Insulin Resistance Atherosclerosis Study. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of Type 2 diabetes: the insulin resistance atherosclerosis study. Diabetes 51: 1131-1137, 2002.
27. Ford ES, Galuska DA, Gillespie C, Will JC, Giles WH, and Dietz WH. C-reactive protein and body mass index in children: findings from the Third National Health and Nutrition Examination Survey, 1988-1994. J Pediatr 138: 486-492, 2001.
28. Ford ESG and Dietz WH. Prevalence of the metabolic syndrome among US adults: findings from the Third National Health and Nutrition Examination Survey. JAMA 287: 356-359, 2002.
29. Fried SK, Bunkin DA, and Greenberg AS. Omental and subcutaneous adipose tissues of obese subjects release interleukin-6: depot difference and regulation by glucocorticoid. J Clin Endocrinol Metab 83: 847-850, 1998.
30. Friedman JM. Obesity in the new millennium. Nature 404: 632-634, 2000.
31. Freeman DJ, Norrie J, Caslake MJ, Gaw A, Ford I, Lowe GD, O'Reilly DS, Packard CJ, and Sattar N; West of Scotland Coronary Prevention Study. C-reactive protein is an independent predictor of risk for the development of diabetes in the West of Scotland Coronary Prevention Study. Diabetes 51: 1596-1600, 2002.
32. Goetze S, Bungenstock A, Czupalla C, Eilers F, Stawowy P, Kintscher U, Spencer-Hansch C, Graf K, Nurnberg B, Law RE, Fleck E, and Grafe M. Leptin induces endothelial cell migration through Akt, which is inhibited by PPARgamma-ligands. Hypertension 40: 748-754, 2002.
33. Haffner SM, Stern MP, Hazuda HP, Mitchell BD, and Patterson JK. Cardiovascular risk factors in confirmed prediabetic individuals. Does the clock for coronary heart disease start ticking before the onset of clinical disease? JAMA 263: 2893-2898, 1990.
34. Heilbronn LK, Noakes M, and Clifton PM. Energy restriction and weight loss on very-low-fat diets reduce C-reactive protein concentrations in obese, healthy women. Arterioscler Thromb Vasc Biol 21: 968-970, 2001.
35. Hermann C, Assmus B, Urbich C, Zeiher AM, and Dimmeler S. Insulin-mediated stimulation of protein kinase Akt: a potent survival signaling cascade for endothelial cells. Arterioscler Thromb Vasc Biol 20: 402-409, 2000.
36. Higashiura K, Ura N, Ohata J, Togashi N, Takagi S, Saitoh S, Murakami H, Takagawa Y, and Shimamoto K. Correlations of adiponectin level with insulin resistance and atherosclerosis in Japanese male populations. Clin Endocrinol (Oxf) 61: 753-759, 2004.
37. Hotamisligil GS. Mechanisms of TNF-alpha-induced insulin resistance. Exp Clin Endocrinol Diabetes 107: 119-125, 1999.
38. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, and Spiegelman BM. Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95: 2409-2415, 1995.
39. Hotamisligil GS, Peraldi P, Budavari A, Ellis R, White MF, and Spiegelman BM. IRS-1-mediated inhibition of insulin receptor tyrosine kinase activity in TNF-alpha- and obesity-induced insulin resistance. Science 271: 665-668, 1996.
40. Hotamisligil GS, Shargill NS, and Spiegelman BM. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259: 87-91, 1993.
41. Hu FB, Stampfer MJ, Haffner SM, Solomon CG, Willett WC, and Manson JE. Elevated risk of cardiovascular disease prior to clinical diagnosis of Type 2 diabetes. Diabetes Care 25: 1129-1134, 2002.
42. Hubert HB, Feinleib M, McNamara PM, and Castelli WP. Obesity as an independent risk factor-for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation 67: 968-977, 1983.
43. Hundal RS, Petersen KF, Mayerson AB, Randhawa PS, Inzucchi S, Shoelson SE, and Shulman GI. Mechanisms by which high-dose aspirin improves glucose metabolism in Type 2 diabetes. J Clin Invest 109: 1321-1326, 2002.
44. Inoguchi T, Li P, Umeda F, Yu HY, Kakimoto M, Imamura M, Aoki T, Etoh T, Hashimoto T, Naruse M, Sano H, Utsumi H, and Nawata H. High glucose level and free fatty acid stimulate reactive oxygen species production through protein kinase C-dependent activation of NAD(P)H oxidase in cultured vascular cells. Diabetes 49: 1939-1945, 2000.
45. Johnson BD, Kip KE, Marroquin OC, Ridker PM, Kelsey SF, Shaw LJ, Pepine CJ, Sharaf B, Bairey Merz CN, Sopko G, Olson MB, and Reis SE; National Heart, Lung, and Blood Institute. Serum amyloid A as a predictor of coronary artery disease and cardiovascular outcome in women: the National Heart, Lung, and Blood Institute-Sponsored Women's Ischemia Syndrome Evaluation (WISE). Circulation 109: 726-732, 2004.
46. Juhan-Vague I and Alessi MC. PAI-1, obesity, insulin resistance and risk of cardiovascular events. Thromb Haemost 78: 656-660, 1997.
47. Kahn BB and Flier JS. Obesity and insulin resistance. J Clin Invest 106: 473-481, 2000.
48. 48a.Knowler WC, Barrett-Connor E, Fowler SE, Hamman RF, Lachin JM, Walker EA, Nathan DM; Diahetes Prevention Program Research Group. Reduction in the incidence of type 2 diabetes with lifestyle intervention or metformin. N Engl J Med 346: 393-403, 2002.
49. Kohler HP and Grant PJ. Plasminogen activator inhibitor type I and coronary artery disease. N Engl J Med 342: 1792-1801, 2000.
50. Konstantinides S, Schafer K, Koschnick S, and Loskutoff DJ. Leptin-dependent platelet aggregation and arterial thrombosis suggests a mechanism for atherothrombotic disease in obesity. J Clin Invest 108: 1533-1540, 2001.
51. Kopelman PG. Obesity as a medical problem. Nature 404: 635-643, 2000.
52. Kopp HP, Kopp CW, Festa A, Krzyzanowska K, Kriwanek S, Minar E, Roka R, and Schernthaner G. Impact of weight loss on inflammatory proteins and their association with the insulin resistance syndrome in morbidly obese patients. Arterioscler Thromb Vasc Biol 23: 1042-1047, 2003.
53. Kubota N, Terauchi Y, Yamauchi T, Kubota T, Moroi M, Matsui J, Eto K, Yamashita T, Kamon J, Satoh H, Yano W, Froguel P, Nagai R, Kimura S, Kadowaki T, and Noda T. Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 277: 25863-25866, 2002.
54. Lau D, Yan H, Ahdel-Hafez M, Kermouni A. Adipokines and the paracrine control of their production in obesity and diabetes. Int J Obes Relat Metab Disord 26: S111, 2002 (Abstract).
55. Lau DC, Schillabeer G, Li ZH, Wong KL, Varzaneh FE, and Tough SC. Paracrine interactions in adipose tissue development and growth. Int J Obes Relat Metab Disord 20, Suppl 3: S16-S25, 1996.
56. Lau DCW. Adipose tissue growth and differentiation: view from the chair. Int J Obes Relat Metab Disord 24, Suppl 4: S20-S22, 2000.
57. Leinonen E, Hurt-Camejo E, Wiklund O, Hulten LM, Hiukka A, and Taskinen MR. Insulin resistance and adiposity correlate with acute-phase reaction and soluble cell adhesion molecules in type 2 diabetes. Atherosclerosis 166: 387-394, 2003.
58. Lemieux I, Pascot A, Prud'homme D, Almeras N, Bogaty P, Nadeau A, Bergeron J, and Despres JP. Elevated C-reactive protein: another component of the atherothrombotic profile of abdominal obesity. Arterioscler Thromb Vasc Biol 21: 961-967, 2001.
59. Lewis GF, Carpentier A, Adeli K, and Giacca A. Disordered fat storage and mobilization in the pathogenesis of insulin resistance and type 2 diabetes. Endocr Rev 23: 201-229, 2002.
60. Li ZH, Carraro R, Gregerman RI, and Lau DC. Adipocyte differentiation factor (ADF): a protein secreted by mature fat cells that induces preadipocyte differentiation in culture. Cell Biol Int 22: 253-270, 1998.
61. Libby P, Ridker PM, and Maseri A. Inflammation and atherosclerosis. Circulation 105: 1135-1143, 2002.
62. Lin Y, Rajala MW, Berger JP, Moller DE, Barzilai N, and Scherer PE. Hyperglycemia-induced production of acute phase reactants in adipose tissue. J Biol Chem 276: 42077-42083, 2001.
63. Lotfreda S, Yang SQ, and Lin HZ. Leptin regulates proinflammatory immune responses. FASEB J 12: 57-65, 1998.
64. Loskutoff DJ and Samad F. The adipocyte and hemostatic balance in obesity: studies of PAI-1. Arterioscler Thromb Vasc Biol 18: 1-6, 1998.
65. Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, and Matsuzawa Y. PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50: 2094-2099, 2001.
66. Marfella R, Quagliaro L, Nappo F, Ceriello A, and Giugliano D. Acute hyperglycemia induces oxidative stress in healthy subjects. J Clin Invest 108: 635-636, 2001.
67. Mather K, Anderson TJ, and Verma S. Insulin action in the vasculature: physiology and pathophysiology. J Vasc Res 38: 415-422, 2001.
68. McGill HC Jr, McMahan CA, Herderick EE, Zieske AW, Malcom GT, Tracy RE, and Strong JP; Pathobiological Determinants of Atherosclerosis in Youth (PDAY) Research Group. Obesity accelerates the progression of coronary atherosclerosis in young men. Circulation 105: 2712-2718, 2002.
69. McLaughlin T, Abbasi F, Lamendola C, Liang L, Reaven G, Schaaf P, and Reaven P. Differentiation between obesity and insulin resistance in the association with C-reactive protein. Circulation 106: 2908-2912, 2002.
70. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS, Klein S, and Coppack SW. Subcutaneous adipose tissue releases iriterleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 82: 4196-4200, 1997.
71. Mohamed-Ali V, Pinkney JH, and Coppack SW. Adipose tissue as an endocrine and paracrine organ. Int J Obes Relat Metab Disord 22: 1145-1158, 1998.
72. Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, and Marks JS. Prevalence of obesity, diabetes and obesity-related health risk factors, 2001. JAMA 289: 76-79, 2003.
73. 1-type angiotensin receptor in oxidative stress and atherogenesis. Part I: oxidative stress and atherogenesis. Circulation 105: 393-396, 2002.
74. Nonogaki K, Fuller GM, Fuentes NL, Moser AH, Staprans I, GrunFeld C, and Feingold KR. Interleukin-6 stimulates hepatic triglyceride secretion in rats. Endocrinology 136: 2143-2149, 1995.
75. Okamoto Y, Kihara S, Ouchi N, Nishida M, Arita Y, Kumada M, Ohashi K, Sakai N, Shimomura I, Kobayashi H, Terasaka N, Inaba T, Funahashi T, and Matsuzawa Y. Adiponectin reduces atherosclerosis in apolipoprotein E-deficient mice. Circulation 106: 2767-2670, 2002.
76. O'Rourke L, Gronning LM, Yeaman SJ, and Shepherd FM. Glucose-dependent regulation of cholesterol ester metabolism in macrophages by insulin and leptin. J Biol Chem 277; 42557-42562, 2002.
77. Arita Y, Kihara S, Ouchi N, Maeda K, Kuriyama H, Okamoto Y, Kumada M, Hotta K, Nishida M, Takahashi M, Nakamura T, Shimomura I, Muraguchi M, Ohmoto Y, Funahashi T, and Matsuzawa Y. Adipocyte-derived plasma protein, adiponectin, suppresses lipid accumulation and class A scavenger receptor expressionin human monocyte-derived macrophages. Circulation 103: 1057-1063, 2001.
78. Ouchi N, Kihara S, Arita Y, Okamoto Y, Maeda K, Kuriyama H, Hotta K, Nishida M, Takahashi M, Muraguchi M, Ohmoto Y, Nakamura T, Yamashita S, Funahashi T, and Matsuzawa Y. Adiponectin, an adipocyte-derived plasma protein, inhibits endothelial NF-kappaB signaling through a cAMP-dependent pathway. Circulation 102: 1296-1301, 2000.
79. Ouchi N, Kihara S, Arita Y, Maeda K, Kuriyama H, Okamoto Y, Hotta K, Nishida M, Takahashi M, Nakamura T, Yamashita S, Funahashi T, and Matsuzawa Y. Novel modulator for endothelial adhesion molecules: adipocyte-derived plasma protein adiponectin. Circulation 100: 2473-2476, 1999.
80. Ouchi N, Kihara S, Funahashi T, Nakamura T, Nishida M, Kumada M, Okamoto Y, Ohashi K, Nagaretani H, Kishida K, Nishizawa H, Maeda N, Kobayashi H, Hiraoka H, and Matsuzawa Y. Reciprocal association of C-reactive protein with adiponectin in blood stream and adipose tissue. Circulation 107: 671-674, 2003.
81. Park HY, Kwon HM, Lim HJ, Hong BK, Lee JY, Park BE, Jang Y, Cho SY, and Kim HS. Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro. Exp Mol Med 33: 95-102, 2001.
82. Pasceri V, Willerson JT, and Yeh ET. Direct proinflammatory effect of C-reactive protein on human endothelial cells. Circulation 102: 2165-2168, 2000.
83. Pasceri V, Wu HD, Willerson JT, and Yeh ET. Modulation of vascular inflammation in vitro and in vivo by peroxisome proliferator-activated receptor-gamma-activators. Circulation 101: 235-238, 2000.
84. Pepys MB and Hirschfield GM. C-reactive protein: a critical update. J Clin Invest 111: 1805-1812, 2003.
85. Pradhan AD, Manson JE, Rifai N, Buring JE, and Ridker PM. C-reactive protein, interleukin 6, and risk of developing type 2 diabetes mellitus. JAMA 286: 327-334, 2001.
86. Quehenberger P, Exner M, Sunder-Plassmann R, Ruzicka K, Bieglmayer C, Endler G, Muellner C, Speiser W, and Wagner O. Leptin induces endothelin-1 in endothelial cells in vitro. Circ Res 90: 711-718, 2002.
87. Reaven GM. Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37: 1595-607, 1988.
88. Ridker PM. Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107: 363-369, 2003.
89. Ridker PM, Buring JE, Cook NR, and Rifai N. C-reactive protein, the metabolic syndrome, and risk of incident cardiovascular events: an 8-year follow-up of 14,719 initially healthy American women. Circulation 107: 391-397, 2003.
90. Rimm EB, Stampfer MJ, Giovannucci E, Ascherio A, Spiegelman D, Colditz GA, and Willett WC. Body size and fat distribution as predictors of coronary heart disease among middle-aged and older US men. Am J Epidemiol 141: 1117-1127, 1995.
91. Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med 340: 115-126, 1999.
92. Roytblat L, Rachinsky M, Fisher A, Greemberg L, Shapira Y, Douvdevani A, and Gelman S. Raised interleukin-6 levels in obese patients. Obes Res 8: 673-675, 2000.
93. Senn JJ, Klover PJ, Nowak IA, Zimmers TA, Koniaris LG, Furlanetto RW, and Mooney RA. Suppressor of cytokine signaling-3 (SOCS-3), a potential mediator of interleukin-6-dependent insulin resistance in hepatocytes. J Biol Chem 278: 13740-13746, 2003.
94. Shillabeer G, Kumar V, Tibbo E, and Lau DC. Arachidonic acid metabolites of the lipoxygenase as well as the cyclooxygenase pathway may be involved in regulating preadipocyte differentiation. Metabolism 47: 461-466, 1998.
95. Shimomura I, Hammer R, and Ikemoto S. Leptin reverses insulin resistance and diabetes mellitus in mice with congenital lipodystrophy. Nature 401: 73-76, 1999.
96. Shoelson SE, Lee J, and Yuan M. Inflammation and the IKKβ/IκB/ NF-κB axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord 27, Suppl 3: S49-S52, 2003.
97. Sierra-Honigmann MR, Nath AK, Murakami C, Garcia-Cardena G, Papapetropoulos A, Sessa WC, Madge LA, Schechner JS, Schwabb MB, Polverini PJ, and Flores-Riveros JR. Biological action of leptin as an angiogenic factor. Science 281: 1683-1386, 1998.
98. Souza SC, Yamamoto MT, Franciosa MD, Lien P, and Greenberg AS. BRL 49653 blocks the lipolytic actions of tumor necrosis factor-alpha: a potential new insulin-sensitizing mechanism for thiazolidinediones. Diabetes 47: 691-695, 1998.
99. Spiegelman BM and Flier JS. Adipogenesis and obesity: rounding out the big picture. Cell 87: 377-389, 1996.
100. Steinberg HO, Tarshoby M, Monestel R, Hook G, Cronin J, Johnson A, Bayazeed B, and Baron AD. Elevated circulating free fatty acid level impair endothelium-dependent vasodilatation. J Clin Invest 100: 1230-1239, 1997.
101. Steppan CM, Bailey ST, Bhat S, Brown EJ, Banerjee RR, Wright CM, Patel HR, Ahima RS, and Lazar MA. The hormone resistin links obesity to diabetes. Nature 409: 307-312, 2001.
102. Tchernof A, Nolan A, Sites CK, Ades PA, and Poehlman ET. Weight loss reduces C-reactive protein levels in obese postmenopausal women. Circulation 105: 564-569, 2002.
103. Tham DM, Martin-McNulty B, Wang YX, Wilson DW, Vergona R, Sullivan ME, Dole W, and Rutledge JC. Angiotensin II is associated with activation of NF-κB-associated genes and downregulation of PPARs. Physiol Genomics 11: 21-30, 2002.
104. Tremblay MS, Katzmarzyk PT, and Willms JD. Temporal trends in overweight and obesity in Canada. Int J Obes 26: 538-543, 2002.
105. Tuomilehto J, Lindstrom J, Eriksson JG, Valle TT, Hamalajnen H, Ilanne-Parikka P, Keinanen-Kiukaanniemi S, Laakso M, Louheranta A, Rastas M, Salminen V, and Uusitupa M; Finnish Diabetes Prevention Study Group. Prevention of type 2 diabetes mellitus by changes in lifestyle among subjects with impaired glucose tolerance. N Engl J Med 344: 1343-1350, 2001.
106. Unger RH. Lipotoxicity in the pathogenesis of obesity-dependent NIDDM. Genetic and clinical implications. Diabetes 44: 863-870, 1995.
107. Uysal KT, Wiesbrock SM, Marino MW, and Hotamisligil GS. Protection from obesity-induced insulin resistance in mice lacking TNF-α function. Nature 389: 610-614, 1997.
108. Verma S and Anderson TJ. Fundamentals of endothelial function for the clinical cardiologist. Circulation 105: 546-549, 2002.
109. Verma S, Li SH, Badiwala MV, Weisel RD, Fedak PW, Li RK, Dhillon B, and Mickle DA. Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein. Circulation 105: 1890-1896, 2002.
110. Verma S, Li SH, Wang CH, Fedak PW, Li RK, Weisel RD, and Mickle DA. Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 108: 736-740, 2003.
111. Verma S, Wang CH, Li SH, Dumont AS, Fedak PW, Badiwala MV, Dhillon B, Weisel RD, Li RK, Mickle DA, and Stewart DJ. A self-fulfilling prophecy: C-reactive protein attenuates nitric oxide production and inhibits angiogenesis. Circulation 106: 913-919, 2002.
112. Verma S, Wang CH, Weisel RD, Badiwala MV, Li SH, Fedak PW, Li RK, and Mickle DA. Hyperglycemia potentiates the proatherogenic effects of C-reactive portein: reversal with rosiglitazone. J Mol Cell Cardiol 35: 417-419, 2003.
113. Visser M, Bouter LM, McQuillan GM, Wener MH, and Harris TB. Elevated C-reactive protein levels in overweight and obese adults. JAMA 282: 2131-2135, 1999.
114. Wajchenberg BL. Subcutaneous and visceral adipose tissue: their relation to the metabolic syndrome. Endocr Rev 21: 697-738, 2000.
115. Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, and Jansson JO. Interleukin-6-deficient mice develop mature-onset obesity. Nat Med 8: 75-79, 2002.
116. Wang CH, Li SH, Weisel RD, Fedak PW, Dumont AS, Szmitko P, Li RK, Mickle DA, and Verma S. C-reactive protein upregulates angiotensin type 1 receptors in vascular smooth muscle. Circulation 107: 1783-1790, 2003.
117. Wang P, Ba ZF, and Chaudry IH. Administration of tumor necrosis factor-alpha in vivo depresses endothelium-dependent relaxation. Am J Physiol Heart Circ Physiol 266: H2535-H2541, 1994.
118. Willett WC, Manson JE, Stampfer MJ, Colditz GA, Rosner B, Speizer FE, and Hennekens CH. Weight, weight change, and coronary heart disease in women. Risk within the"'normal" weight range. JAMA 273: 461-465, 1995.
119. World Health Organization. Obesity. Preventing and managing the global epidemic. Report of a WHO consultation on obesity. Geneva: WHO, 1998, p. 1-276.
120. Yamagishi SI, Edelstein D, Du XL, Kaneda Y, Guzman M, and Brownlee M. Leptin induces mitochondrial superoxide production and monocyte chemoattractant protein-1 expression in aortic endothelial cells by increasing fatty acid oxidation via protein kinase A. J Biol Chem 276: 25096-25100, 2001.
121. Yamamoto Y, Hirose H, Saito I, Tomita M, Taniyama M, Matsubara K, Okazaki Y, Ishii T, Nishikai K, and Saruta T. Correlation of the adipocyte-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) 103: 137-142, 2002.
122. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, and Kadowaki T. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7: 941-946, 2001.
123. Yan H, Aziz E, Shillabeer G, Wong A, Shanghavi D, Kermouni A, Abdel-Hafez M, and Lau DC. Nitric oxide promotes differentiation of rat white adipocytes in culture. J Lipid Res 43: 2123-2129, 2002.
124. Yang WS, Lee WJ, Funahashi T, Tanaka S, Matsuzawa Y, Chao CL, Chen CL, Tai TY, and Chuang LM. Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 86: 3815-3819, 2001.
125. Yu JG, Javorschi S, Hevener AL, Kruszynska YT, Norman RA, Sinha M, and Olefsky JM. The effect of thiazolidinediones on plasma adiponectin levels in normal, obese, and type 2 diabetic subjects. Diabetes 51: 2968-2974, 2002.
126. Yuan M, Konstantopoulos N, Lee J, Hansen L, Li ZW, Karin M, and Shoelson SE. Reversal of obesity- and diet-induced insulin resistance with salicylates or targeted disruption of Ikkbeta. Science 293: 1673-1677, 2001.
127. Yudkin JS, Stehouwer CD, Emeis JJ, and 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 19: 972-978, 1999.