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Adiposopathy is a more rational treatment target for metabolic disease than obesity alone

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Abstract

Current guidelines recommend that weight-loss therapy should be primarily based upon specific body mass index (BMI) cut-off limits. However, in the adipocentric paradigm, it is acknowledged that co-morbidities, such as type 2 diabetes mellitus, hypertension, and dyslipidemia, occur at all levels of BMI. Excessive fat mass (adiposity) in genetically susceptible individuals results in fat dysfunction (adiposopathy), which then contributes to metabolic disorders that increase the risk of atherosclerotic cardiovascular disease. In this paradigm, the term “anti-obesity” treatment might best be replaced by “anti-adiposopathy” treatment, wherein the focus is not based solely on BMI, but instead directed towards physiologically improving fat cell function and clinically improving the metabolic health of patients. This may occur through appropriate diet, physical exercise, and other lifestyle changes, and/or from drug therapies. Cannabinoid receptor antagonists and peroxisome proliferator activated receptor agonists are examples of agents that physiologically improve fat function and clinically improve metabolic disease.

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References and Recommended Reading

  1. Bays H, Abate N, Chandalia M: Adiposopathy: sick fat causes high blood sugar, high blood pressure, and dyslipidemia. Future Cardiol 2005, 1:39–59.

    Article  CAS  Google Scholar 

  2. Kershaw EE, Flier JS: Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2004, 89:2548–2556.

    Article  PubMed  CAS  Google Scholar 

  3. Bays H: Adiposopathy, metabolic syndrome, quantum physics, general relativity, chaos and the Theory of Everything. Expert Rev Cardiovasc Ther 2005, 3:393–404.

    Article  PubMed  CAS  Google Scholar 

  4. Kahn R, Buse J, Ferrannini E, Stern M: The Metabolic Syndrome: Time for a Critical Appraisal: Joint statement from the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2005, 28:2289–2304.

    Article  PubMed  Google Scholar 

  5. Stern MP, Williams K, Gonzalez-Villalpando C, et al.: Does the metabolic syndrome improve identification of individuals at risk of type 2 diabetes and/or cardiovascular disease? Diabetes Care 2004, 27:2676–2681.

    Article  PubMed  Google Scholar 

  6. National Heart, Lung and Blood Institute: The practical guide to the identification, evaluation and treatment of overweight and obesity in adults. http://www.nhlbi.nih.gov/guidelines/obesity/prctgd_b.pdf. Accessed December 23, 2005.

  7. Snow V, Barry P, Fitterman N, et al.: Pharmacologic and surgical management of obesity in primary care: a clinical practice guideline from the American College of Physicians. Ann Intern Med 2005, 142:525–531.

    PubMed  Google Scholar 

  8. Grundy SM: What is the contribution of obesity to the metabolic syndrome? Endocrinol Metab Clin North Am 2004, 33:267–282.

    Article  PubMed  Google Scholar 

  9. Franks PW, Brage S, Luan J, et al.: Leptin predicts a worsening of the features of the metabolic syndrome independently of obesity. Obes Res 2005, 13:1476–1484.

    PubMed  CAS  Google Scholar 

  10. Karelis AD, St-Pierre DH, Conus F, et al.: Metabolic and body composition factors in subgroups of obesity: what do we know? J Clin Endocrinol Metab 2004, 89:2569–2575.

    Article  PubMed  CAS  Google Scholar 

  11. Haque WA, Shimomura I, Matsuzawa Y, Garg A: Serum adiponectin and leptin levels in patients with lipody-strophies. J Clin Endocrinol Metab 2002, 87:2395.

    Article  PubMed  CAS  Google Scholar 

  12. Meijssen S, Cabezas MC, Twickler TB, et al.: In vivo evidence of defective postprandial and postabsorptive free fatty acid metabolism in familial combined hyperlipidemia. J Lipid Res 2000, 41:1096–1102.

    PubMed  CAS  Google Scholar 

  13. Salans LB, Dougherty JW: The effect of insulin upon glucose metabolism by adipose cells of different size. Influence of cell lipid and protein content, age, and nutritional state. J Clin Invest 1971, 50:1399–1410.

    PubMed  CAS  Google Scholar 

  14. Smith U: Effect of cell size on lipid synthesis by human adipose tissue in vitro. J Lipid Res 1971, 12:65–70.

    PubMed  CAS  Google Scholar 

  15. Julius U, Leonhardt W, Schneider H, et al.: Basal and stimulated hyperinsulinemia in obesity: relationship to adipose-cell size. Endokrinologie 1979, 73:214–220.

    PubMed  CAS  Google Scholar 

  16. Haller H, Leonhardt W, Hanefeld M, Julius U: Relationship between adipocyte hypertrophy and metabolic disturbances. Endokrinologie 1979, 74:63–72.

    PubMed  CAS  Google Scholar 

  17. Schneider BS, Faust IM, Hemmes R, Hirsch J: Effects of altered adipose tissue morphology on plasma insulin levels in the rat. Am J Physiol 1981, 240:E358-E362.

    PubMed  CAS  Google Scholar 

  18. Gregoire FM, Smas CM, Sul HS: Understanding adipocyte differentiation. Physiol Rev 1998, 78:783–809.

    PubMed  CAS  Google Scholar 

  19. Nadler ST, Stoehr JP, Schueler KL, et al.: The expression of adipogenic genes is decreased in obesity and diabetes mellitus. Proc Natl Acad Sci U S A 2000, 97:11371–11376.

    Article  PubMed  CAS  Google Scholar 

  20. Heilbronn L, Smith SR, Ravussin E: Failure of fat cell proliferation, mitochondrial function and fat oxidation results in ectopic fat storage, insulin resistance and type II diabetes mellitus. Int J Obes Relat Metab Disord 2004, 28(Suppl 4):S12-S21.

    Article  PubMed  CAS  Google Scholar 

  21. Hissin PJ, Foley JE, Wardzala LJ, et al.: Mechanism of insulin-resistant glucose transport activity in the enlarged adipose cell of the aged, obese rat. J Clin Invest 1982, 70:780–790.

    PubMed  CAS  Google Scholar 

  22. Le LS, Krief S, Farnier C, et al.: Cholesterol, a cell size-dependent signal that regulates glucose metabolism and gene expression in adipocytes. J Biol Chem 2001, 276:16904–16910.

    Article  Google Scholar 

  23. Bays H, Mandarino L, DeFronzo RA: Role of the adipocyte, free fatty acids, and ectopic fat in pathogenesis of type 2 diabetes mellitus: peroxisomal proliferator-activated receptor agonists provide a rational therapeutic approach. J Clin Endocrinol Metab 2004, 89:463–478.

    Article  PubMed  CAS  Google Scholar 

  24. Morrison RF, Farmer SR: Hormonal signaling and transcriptional control of adipocyte differentiation. J Nutr 2000, 130:3116S-3121S.

    PubMed  CAS  Google Scholar 

  25. Weisberg SP, McCann D, Desai M, et al.: Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 2003, 112:1796–1808.

    Article  PubMed  CAS  Google Scholar 

  26. Wellen KE, Hotamisligil GS: Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 2003, 112:1785–1788.

    Article  PubMed  CAS  Google Scholar 

  27. Wisse BE: The inflammatory syndrome: the role of adipose tissue cytokines in metabolic disorders linked to obesity. J Am Soc Nephrol 2004, 15:2792–2800.

    Article  PubMed  CAS  Google Scholar 

  28. Xu H, Barnes GT, Yang Q, 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.

    Article  PubMed  CAS  Google Scholar 

  29. Libby P, Theroux P: Pathophysiology of coronary artery disease. Circulation 2005, 111:3481–3488.

    Article  PubMed  Google Scholar 

  30. Shishehbor MH, Bhatt DL: Inflammation and atherosclerosis. Curr Atheroscler Rep 2004, 6:131–139.

    Article  PubMed  Google Scholar 

  31. Berg AH, Scherer PE: Adipose tissue, inflammation, and cardiovascular disease. Circ Res 2005, 96:939–949.

    Article  PubMed  CAS  Google Scholar 

  32. World Health Organization. Obesity and overweight facts. http://www.who.int/hpr/NPH/docs/gs_obesity.pdf. Accessed December 23, 2005.

  33. Jemal A, Ward E, Hao Y, Thun M: Trends in the leading causes of death in the United States, 1970–2002. JAMA 2005, 294:1255–1259.

    Article  PubMed  CAS  Google Scholar 

  34. Grundy SM: Obesity, metabolic syndrome, and cardiovascular disease. J Clin Endocrinol Metab 2004, 89:2595–2600.

    Article  PubMed  CAS  Google Scholar 

  35. Bray GA: Medical consequences of obesity. J Clin Endocrinol Metab 2004, 89:2583–2589.

    Article  PubMed  CAS  Google Scholar 

  36. Matsuzawa Y: Adipocytokines: emerging therapeutic targets. Curr Atheroscler Rep 2005, 7:58–62.

    Article  PubMed  CAS  Google Scholar 

  37. Miller WM, Nori Janosz KE, Yanez J, McCullough PA: Effects of weight loss and pharmacotherapy on inflammatory markers of cardiovascular disease. Expert Rev Cardiovasc Ther 2005, 3:743–759.

    Article  PubMed  CAS  Google Scholar 

  38. Ferroni P, Basili S, Falco A, Davi G: Inflammation, insulin resistance, and obesity. Curr Atheroscler Rep 2004, 6:424–431.

    Article  PubMed  Google Scholar 

  39. Fantuzzi G: Adipose tissue, adipokines, and inflammation. J Allergy Clin Immunol 2005, 115:911–919.

    Article  PubMed  CAS  Google Scholar 

  40. Santos AC, Lopes C, Guimaraes JT, Barros H: Central obesity as a major determinant of increased high-sensitivity C-reactive protein in metabolic syndrome. Int J Obes 2005, 29:1452–1456.

    Article  CAS  Google Scholar 

  41. Oguma Y, Sesso HD, Paffenbarger RS Jr, Lee IM: Weight change and risk of developing type 2 diabetes. Obes Res 2005, 13:945–951.

    PubMed  Google Scholar 

  42. Wolk R, Shamsuzzaman AS, Somers VK: Obesity, sleep apnea, and hypertension. Hypertension 2003, 42:1067–1074.

    Article  PubMed  CAS  Google Scholar 

  43. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A, et al.: Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci U S A 2003, 100:14211–14216.

    Article  PubMed  CAS  Google Scholar 

  44. Coatmellec-Taglioni G, Ribiere C: Factors that influence the risk of hypertension in obese individuals. Curr Opin Nephrol Hypertens 2003, 12:305–308.

    Article  PubMed  CAS  Google Scholar 

  45. Straznicky NE, Lambert EA, Lambert GW, et al.: Effects of dietary weight loss on sympathetic activity and cardiac risk factors associated with the metabolic syndrome. J Clin Endocrinol Metab 2005, 90:5998–6005.

    Article  PubMed  CAS  Google Scholar 

  46. Brown CD, Higgins M, Donato KA, et al.: Body mass index and the prevalence of hypertension and dyslipidemia. Obes Res 2000, 8:605–619.

    PubMed  CAS  Google Scholar 

  47. 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) final report: Circulation 2002, 106:3143–3421.

  48. Viguerie N, Vidal H, Arner P, et al.: Adipose tissue gene expression in obese subjects during low-fat and high-fat hypocaloric diets. Diabetologia 2005, 48:123–131.

    Article  PubMed  CAS  Google Scholar 

  49. Arvidsson E, Viguerie N, Andersson I, et al.: Effects of different hypocaloric diets on protein secretion from adipose tissue of obese women. Diabetes 2004, 53:1966–1971.

    Article  PubMed  CAS  Google Scholar 

  50. Giannopoulou I, Ploutz-Snyder LL, Carhart R, et al.: Exercise is required for visceral fat loss in postmenopausal women with type 2 diabetes. J Clin Endocrinol Metab 2005, 90:1511–1518.

    Article  PubMed  CAS  Google Scholar 

  51. You T, Berman DM, Ryan AS, Nicklas BJ: Effects of hypocaloric diet and exercise training on inflammation and adipocyte lipolysis in obese postmenopausal women. J Clin Endocrinol Metab 2004, 89:1739–1746.

    Article  PubMed  CAS  Google Scholar 

  52. Norris SL, Zhang X, Avenell A, et al.: Long-term effectiveness of lifestyle and behavioral weight loss interventions in adults with type 2 diabetes: a meta-analysis. Am J Med 2004, 117:762–774.

    Article  PubMed  Google Scholar 

  53. Aucott L, Poobalan A, Smith WC, et al.: Weight loss in obese diabetic and non-diabetic individuals and long-term diabetes outcomes—a systematic review. Diabetes Obes Metab 2004, 6:85–94.

    Article  PubMed  CAS  Google Scholar 

  54. Aucott L, Poobalan A, Smith WC, et al.: Effects of weight loss in overweight/obese individuals and long-term hypertension outcomes: a systematic review. Hypertension 2005, 45:1035–1041.

    Article  PubMed  CAS  Google Scholar 

  55. Boden G, Sargrad K, Homko C, et al.: Effect of a low-carbohydrate diet on appetite, blood glucose levels, and insulin resistance in obese patients with type 2 diabetes. Ann Intern Med 2005, 142:403–411.

    PubMed  CAS  Google Scholar 

  56. Stone NJ, Kushner R: Effects of dietary modification and treatment of obesity. Emphasis on improving vascular outcomes. Med Clin North Am 2000, 84:95–122.

    Article  PubMed  CAS  Google Scholar 

  57. Giannopoulou I, Fernhall B, Carhart R, et al.: Effects of diet and/or exercise on the adipocytokine and inflammatory cytokine levels of postmenopausal women with type 2 diabetes. Metabolism 2005, 54:866–875.

    Article  PubMed  CAS  Google Scholar 

  58. Petersen KF, Befroy D, Dufour S, et al.: Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 2003, 300:1140–1142.

    Article  PubMed  CAS  Google Scholar 

  59. Catalano KJ, Bergman RN, Ader M: Increased susceptibility to insulin resistance associated with abdominal obesity in aging rats. Obes Res 2005, 13:11–20.

    PubMed  CAS  Google Scholar 

  60. Eckel RH: The dietary approach to obesity: is it the diet or the disorder? JAMA 2005, 293:96–97.

    Article  PubMed  CAS  Google Scholar 

  61. Li Z, Maglione M, Tu W, et al.: Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005, 142:532–546.

    PubMed  CAS  Google Scholar 

  62. Bays HE: Current and investigational antiobesity agents and obesity therapeutic treatment targets. Obes Res 2004, 12:1197–1211.

    PubMed  CAS  Google Scholar 

  63. Bays H, Dujovne C: Anti-obesity drug development. Expert Opin Investig Drugs 2002, 11:1189–1204.

    Article  PubMed  Google Scholar 

  64. Valsamakis G, McTernan PG, Chetty R, 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.

    Article  PubMed  CAS  Google Scholar 

  65. Hsieh CJ, Wang PW, Liu RT, et al.: Orlistat for obesity: benefits beyond weight loss. Diabetes Res Clin Pract 2005, 67:78–83.

    Article  PubMed  CAS  Google Scholar 

  66. Kiortsis DN, Filippatos TD, Elisaf MS: The effects of orlistat on metabolic parameters and other cardiovascular risk factors. Diabetes Metab 2005, 31:15–22.

    Article  PubMed  CAS  Google Scholar 

  67. Kelley DE, Kuller LH, McKolanis TM, et al.: Effects of moderate weight loss and orlistat on insulin resistance, regional adiposity, and fatty acids in type 2 diabetes. Diabetes Care 2004, 27:33–40.

    Article  PubMed  CAS  Google Scholar 

  68. Tan KC, Tso AW, Tam SC, et al.: Acute effect of orlistat on post-prandial lipaemia and free fatty acids in overweight patients with Type 2 diabetes mellitus. Diabet Med 2002, 19:944–948.

    Article  PubMed  CAS  Google Scholar 

  69. Yesilbursa D, Serdar A, Heper Y, et al.: The effect of orlistat-induced weight loss on interleukin-6 and C-reactive protein levels in obese subjects. Acta Cardiol 2005, 60:265–269.

    Article  PubMed  Google Scholar 

  70. Samuelsson L, Gottsater A, Lindgarde F: Decreasing levels of tumour necrosis factor alpha and interleukin 6 during lowering of body mass index with orlistat or placebo in obese subjects with cardiovascular risk factors. Diabetes Obes Metab 2003, 5:195–201.

    Article  PubMed  CAS  Google Scholar 

  71. Halpern A, Mancini MC: Diabesity: are weight loss medications effective? Treat Endocrinol 2005, 4:65–74.

    Article  PubMed  CAS  Google Scholar 

  72. Didangelos TP, Thanopoulou AK, Bousboulas SH, et al.: The ORLIstat and CArdiovascular risk profile in patients with metabolic syndrome and type 2 DIAbetes (ORLICARDIA) Study. Curr Med Res Opin 2004, 20:1393–1401.

    Article  PubMed  CAS  Google Scholar 

  73. Guy-Grand B, Drouin P, Eschwege E, et al.: Effects of orlistat on obesity-related diseases—a six-month randomized trial. Diabetes Obes Metab 2004, 6:375–383.

    Article  PubMed  CAS  Google Scholar 

  74. Bakris G, Calhoun D, Egan B, et al.: Orlistat improves blood pressure control in obese subjects with treated but inadequately controlled hypertension. J Hypertens 2002, 20:2257–2267.

    Article  PubMed  CAS  Google Scholar 

  75. Rossner S, Sjostrom L, Noack R, et al.: Weight loss, weight maintenance, and improved cardiovascular risk factors after 2 years treatment with orlistat for obesity. European Orlistat Obesity Study Group. Obes Res 2000, 8:49–61.

    Article  PubMed  CAS  Google Scholar 

  76. Hutton B, Fergusson D: Changes in body weight and serum lipid profile in obese patients treated with orlistat in addition to a hypocaloric diet: a systematic review of randomized clinical trials. Am J Clin Nutr 2004, 80:1461–1468.

    PubMed  CAS  Google Scholar 

  77. Sjostrom L, Rissanen A, Andersen T, et al.: Randomised placebo-controlled trial of orlistat for weight loss and prevention of weight regain in obese patients. European Multicentre Orlistat Study Group. Lancet 1998, 352:167–172.

    Article  PubMed  CAS  Google Scholar 

  78. Mittendorfer B, Ostlund RE Jr, Patterson BW, Klein S: Orlistat inhibits dietary cholesterol absorption. Obes Res 2001, 9:599–604.

    PubMed  CAS  Google Scholar 

  79. Filippatos TD, Kiortsis DN, Liberopoulos EN, et al.: A review of the metabolic effects of sibutramine. Curr Med Res Opin 2005, 21:457–468.

    Article  PubMed  CAS  Google Scholar 

  80. Kim DM, Yoon SJ, Ahn CW, et al.: Sibutramine improves fat distribution and insulin resistance, and increases serum adiponectin levels in Korean obese nondiabetic premenopausal women. Diabetes Res Clin Pract 2004, 66(Suppl 1):S139-S144.

    Article  PubMed  CAS  Google Scholar 

  81. Day C, Bailey CJ: Effect of the antiobesity agent sibutramine in obese-diabetic ob/ob mice. Int J Obes Relat Metab Disord 1998, 22:619–623.

    Article  PubMed  CAS  Google Scholar 

  82. Hung YJ, Chen YC, Pei D, et al.: Sibutramine improves insulin sensitivity without alteration of serum adiponectin in obese subjects with type 2 diabetes. Diabet Med 2005, 22:1024–1030.

    Article  PubMed  CAS  Google Scholar 

  83. McLaughlin T, Abbasi F, Lamendola C, et al.: Metabolic changes following sibutramine-assisted weight loss in obese individuals: role of plasma free fatty acids in the insulin resistance of obesity. Metabolism 2001, 50:819–824.

    Article  PubMed  CAS  Google Scholar 

  84. Fujioka K, Seaton TB, Rowe E, et al.: Weight loss with sibutramine improves glycaemic control and other metabolic parameters in obese patients with type 2 diabetes mellitus. Diabetes Obes Metab 2000, 2:175–187.

    Article  PubMed  CAS  Google Scholar 

  85. Finer N, Bloom SR, Frost GS, et al.: Sibutramine is effective for weight loss and diabetic control in obesity with type 2 diabetes: a randomised, double-blind, placebo-controlled study. Diabetes Obes Metab 2000, 2:105–112.

    Article  PubMed  CAS  Google Scholar 

  86. Vettor R, Serra R, Fabris R, et al.: Effect of sibutramine on weight management and metabolic control in type 2 diabetes: a meta-analysis of clinical studies. Diabetes Care 2005, 28:942–949.

    Article  PubMed  CAS  Google Scholar 

  87. Dujovne CA, Zavoral JH, Rowe E, Mendel CM: Effects of sibutramine on body weight and serum lipids: a double-blind, randomized, placebo-controlled study in 322 overweight and obese patients with dyslipidemia. Am Heart J 2001, 142:489–497.

    Article  PubMed  CAS  Google Scholar 

  88. Jordan J, Scholze J, Matiba B, et al.: Influence of Sibutramine on blood pressure: evidence from placebo-controlled trials. Int J Obes 2005, 29:509–516.

    CAS  Google Scholar 

  89. Birkenfeld AL, Schroeder C, Pischon T, et al.: Paradoxical effect of sibutramine on autonomic cardiovascular regulation in obese hypertensive patients—sibutramine and blood pressure. Clin Auton Res 2005, 15:200–206.

    Article  PubMed  Google Scholar 

  90. Ryan DH: Clinical use of sibutramine. Drugs Today 2004, 40:41–54.

    Article  PubMed  CAS  Google Scholar 

  91. Boden G, Laakso M: Lipids and glucose in type 2 diabetes: what is the cause and effect? Diabetes Care 2004, 27:2253–2259.

    Article  PubMed  CAS  Google Scholar 

  92. Havel PJ: Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 2004, 53(Suppl 1):S143-S151.

    Article  PubMed  CAS  Google Scholar 

  93. Rasouli N, Yao-Borengasser A, Miles LM, et al.: Increased plasma adiponectin in response to pioglitazone does not result from increased gene expression. Am J Physiol Endocrinol Metab 2005, 290:E42-E46.

    Article  PubMed  CAS  Google Scholar 

  94. Tilg H, Wolf AM: Adiponectin: a key fat-derived molecule regulating inflammation. Expert Opin Ther Targets 2005, 9:245–251.

    Article  PubMed  CAS  Google Scholar 

  95. Bogacka I, Xie H, Bray GA, Smith SR: The effect of pioglitazone on peroxisome proliferator-activated receptor-gamma target genes related to lipid storage in vivo. Diabetes Care 2004, 27:1660–1667.

    Article  PubMed  CAS  Google Scholar 

  96. McTernan PG, Fisher FM, Valsamakis G, 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.

    Article  PubMed  CAS  Google Scholar 

  97. Hetzel J, Balletshofer B, Rittig K, et al.: Rapid effects of rosiglitazone treatment on endothelial function and inflammatory biomarkers. Arterioscler Thromb Vasc Biol 2005, 25:1804–1809.

    Article  PubMed  CAS  Google Scholar 

  98. Chilton R, Chiquette E: Thiazolidinediones and cardiovascular disease. Curr Atheroscler Rep 2005, 7:115–120.

    Article  PubMed  CAS  Google Scholar 

  99. Lebovitz HE: Rationale for and role of thiazolidinediones in type 2 diabetes mellitus. Am J Cardiol 2002, 90:34G-41G.

    Article  PubMed  CAS  Google Scholar 

  100. Dormandy JA, Charbonnel B, Eckland DJ, 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.

    Article  PubMed  CAS  Google Scholar 

  101. Buse JB: Muraglitazar, a dual alpha/gamma PPAR activator: a randomized, double-blind, placebo-controlled, 24-week monotherapy trial in adult patients with type 2 diabetes. Clin Ther 2005, 27:1181–1195.

    Article  PubMed  CAS  Google Scholar 

  102. Fagerberg B, Edwards S, Halmos T, et al.: Tesaglitazar, a novel dual peroxisome proliferators-activated receptor alpha/gamma agonist, dose-dependently improves the metabolic abnormalities associated with insulin resistance in a non-diabetic population. Diabetologia 2005, 48:1716–1725.

    Article  PubMed  CAS  Google Scholar 

  103. Fredenrich A, Grimaldi PA: PPAR delta: an uncompletely known nuclear receptor. Diabetes Metab 2005, 31:23–27.

    Article  PubMed  CAS  Google Scholar 

  104. Osei-Hyiaman D, Depetrillo M, Pacher P, et al.: Endocannabinoid activation at hepatic CB1 receptors stimulates fatty acid synthesis and contributes to diet-induced obesity. J Clin Invest 2005, 115:1298–1305.

    Article  PubMed  CAS  Google Scholar 

  105. Poirier B, Bidouard JP, Cadrouvele C, et al.: The anti-obesity effect of rimonabant is associated with an improved serum lipid profile. Diabetes Obes Metab 2005, 7:65–72.

    Article  PubMed  CAS  Google Scholar 

  106. Bensaid M, Gary-Bobo M, Esclangon A, et al.: The cannabinoid CB1 receptor antagonist SR141716 increases Acrp30 mRNA expression in adipose tissue of obese fa/fa rats and in cultured adipocyte cells. Mol Pharmacol 2003, 63:908–914.

    Article  PubMed  CAS  Google Scholar 

  107. Anthenelli RM: Effects of rimonabant in the reduction of major cardiovascular risk factors. Results from the STRATUS-US Trial (smoking cessation in smokers motivated to quit) and the RIO-LIPIDS Trial (weight reducing and metabolic effects in overweight/obese patients with dyslipidemia. Paper presented at American College of Cardiology 53rd Annual Scientific Sessions, New Orleans, March 7–9, 2004.

  108. Ravinet TC, Arnone M, Delgorge C, et al.: Anti-obesity effect of SR141716, a CB1 receptor antagonist, in diet-induced obese mice. Am J Physiol Regul Integr Comp Physiol 2003, 284:R345-R353.

    Google Scholar 

  109. Van Gaal LF, Rissanen AM, Scheen AJ, et al.: Effects of the cannabinoid-1 receptor blocker rimonabant on weight reduction and cardiovascular risk factors in overweight patients: 1-year experience from the RIO-Europe study. Lancet 2005, 365:1389–1397.

    Article  PubMed  CAS  Google Scholar 

  110. Van Gaal L: 2 year data from the RIO-Europe Study: metabolic effects of rimonabant in overweight/obese patients. Paper presented at American College of Cardiology Annual Scientific Session 2005, Orlando, Florida, March 6–9.

  111. Pi-Sunyer FX: Effect of rimonabant on weight reduction and weight maintenance: RIO-North America (RIO-AN) Trial. Paper presented at American Heart Association Scientific Sessions 2004, November 7–10, New Orleans, 2005.

  112. Correa F, Mestre L, Molina-Holgado E, et al.: The role of cannabinoid system on immune modulation: therapeutic implications on CNS inflammation. Mini Rev Med Chem 2005, 5:671–675.

    Article  PubMed  CAS  Google Scholar 

  113. Jackson SJ, Diemel LT, Pryce G, Baker D: Cannabinoids and neuroprotection in CNS inflammatory disease. J Neurol Sci 2005, 233:21–25.

    Article  PubMed  CAS  Google Scholar 

  114. Massa F, Storr M, Lutz B: The endocannabinoid system in the physiology and pathophysiology of the gastrointestinal tract. J Mol Med 2005, 83:944–954.

    Article  PubMed  CAS  Google Scholar 

  115. Sheng WS, Hu S, Min X, et al.: Synthetic cannabinoid WIN55,212-2 inhibits generation of inflammatory mediators by IL-1beta-stimulated human astrocytes. Glia 2005, 49:211–219.

    Article  PubMed  Google Scholar 

  116. Klein TW, Newton C, Larsen K, et al.: Cannabinoid receptors and T helper cells. J Neuroimmunol 2004, 147:91–94.

    Article  PubMed  CAS  Google Scholar 

  117. van Oosten BW, Killestein J, Mathus-Vliegen EM, Polman CH: Multiple sclerosis following treatment with a cannabinoid receptor-1 antagonist. Mult Scler 2004, 10:330–331.

    Article  PubMed  Google Scholar 

  118. Scheen AJ: Rimonabant in patients with type 2 diabetes: results from RIO-Diabetes. American Diabetes Association 65th Annual Scientific Sessions Late Breaking Clinical Trials 2005, San Diego, CA, June 12.

  119. Flegal KM, Graubard BI, Williamson DF, Gail MH: Excess deaths associated with underweight, overweight, and obesity. Obstet Gynecol Surv 2005, 60:593–595.

    Article  Google Scholar 

  120. Gregg EW, Cheng YJ, Cadwell BL, et al.: Secular trends in cardiovascular disease risk factors according to body mass index in US adults. JAMA 2005, 293:1868–1874.

    Article  PubMed  CAS  Google Scholar 

  121. Abuissa H, Jones PG, Marso SP, O’keefe JH Jr.: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers for prevention of type 2 diabetes a meta-analysis of randomized clinical trials. J. Am Coll Cardiol 2005, 46:821–826.

    Article  PubMed  CAS  Google Scholar 

  122. Koh KK, Quon MJ, Han SH, et al.: Vascular and metabolic effects of combined therapy with ramipril and simvastatin in patients with type 2 diabetes. Hypertension 2005, 45:1088–1093.

    Article  PubMed  CAS  Google Scholar 

  123. Clasen R, Schupp M, Foryst-Ludwig A, et al.: PPARgamma-activating angiotensin type-1 receptor blockers induce adiponectin. Hypertension 2005, 46:137–143.

    Article  PubMed  CAS  Google Scholar 

  124. National Center for Health Statistics: National Health and Nutrition Examination Survey (NHANES) 1999 – 2004 Content. Atlanta, GA: Centers for Disease Control; 2004.

    Google Scholar 

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Bays, H., Dujovne, C.A. Adiposopathy is a more rational treatment target for metabolic disease than obesity alone. Curr Atheroscler Rep 8, 144–156 (2006). https://doi.org/10.1007/s11883-006-0052-6

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  • DOI: https://doi.org/10.1007/s11883-006-0052-6

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