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Gluteofemoral body fat as a determinant of metabolic health

International Journal of Obesity volume 34, pages 949–959 (2010)Cite this article

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Abstract

Body fat distribution is an important metabolic and cardiovascular risk factor, because the proportion of abdominal to gluteofemoral body fat correlates with obesity-associated diseases and mortality. Here, we review the evidence and possible mechanisms that support a specific protective role of gluteofemoral body fat. Population studies show that an increased gluteofemoral fat mass is independently associated with a protective lipid and glucose profile, as well as a decrease in cardiovascular and metabolic risk. Studies of adipose tissue physiology in vitro and in vivo confirm distinct properties of the gluteofemoral fat depot with regards to lipolysis and fatty acid uptake: in day-to-day metabolism it appears to be more passive than the abdominal depot and it exerts its protective properties by long-term fatty acid storage. Further, a beneficial adipokine profile is associated with gluteofemoral fat. Leptin and adiponectin levels are positively associated with gluteofemoral fat while the level of inflammatory cytokines is negatively associated. Finally, loss of gluteofemoral fat, as observed in Cushing's syndrome and lipodystrophy is associated with an increased metabolic and cardiovascular risk. This underlines gluteofemoral fat's role as a determinant of health by the long-term entrapment of excess fatty acids, thus protecting from the adverse effects associated with ectopic fat deposition.

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References

  1. Willett WC, Dietz WH, Colditz GA . Guidelines for healthy weight. N Engl J Med 1999; 341: 427–434.

    CAS  PubMed  Google Scholar 

  2. Canoy D, Luben R, Welch A, Bingham S, Wareham N, Day N et al. Fat distribution, body mass index and blood pressure in 22 090 men and women in the Norfolk cohort of the European prospective investigation into cancer and nutrition (EPIC-Norfolk) study. J Hypertens 2004; 22: 2067–2074.

    CAS  PubMed  Google Scholar 

  3. Grundy SM, Adams-Huet B, Vega GL . Variable contributions of fat content and distribution to metabolic syndrome risk factors. Metab Syndr Relat Disord 2008; 6: 281–288.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Yusuf S, Hawken S, Ounpuu S, Bautista L, Franzosi MG, Commerford P et al. Obesity and the risk of myocardial infarction in 27 000 participants from 52 countries: a case-control study. Lancet 2005; 366: 1640–1649.

    Article  PubMed  Google Scholar 

  5. Meisinger C, Doring A, Thorand B, Heier M, Lowel H . Body fat distribution and risk of type 2 diabetes in the general population: are there differences between men and women? The monica/kora augsburg cohort study. Am J Clin Nutr 2006; 84: 483–489.

    CAS  PubMed  Google Scholar 

  6. Taksali SE, Caprio S, Dziura J, Dufour S, Cali AM, Goodman TR et al. High visceral and low abdominal subcutaneous fat stores in the obese adolescent: a determinant of an adverse metabolic phenotype. Diabetes 2008; 57: 367–371.

    CAS  PubMed  Google Scholar 

  7. Hayashi T, Boyko EJ, McNeely MJ, Leonetti DL, Kahn SE, Fujimoto WY . Visceral adiposity, not abdominal subcutaneous fat area, is associated with an increase in future insulin resistance in japanese americans. Diabetes 2008; 57: 1269–1275.

    CAS  PubMed  Google Scholar 

  8. Sam S, Haffner S, Davidson MH, D’Agostino Sr RB, Feinstein S, Kondos G et al. Relationship of abdominal visceral and subcutaneous adipose tissue with lipoprotein particle number and size in type 2 diabetes. Diabetes 2008; 57: 2022–2027.

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Frayn KN . Visceral fat and insulin resistance--causative or correlative? Br J Nutr 2000; 83 (Suppl 1): S71–S77.

    CAS  PubMed  Google Scholar 

  10. Miles JM, Jensen MD . Counterpoint: visceral adiposity is not causally related to insulin resistance. Diabetes Care 2005; 28: 2326–2328.

    PubMed  Google Scholar 

  11. Perrini S, Laviola L, Cignarelli A, Melchiorre M, De Stefano F, Caccioppoli C et al. Fat depot-related differences in gene expression, adiponectin secretion, and insulin action and signalling in human adipocytes differentiated in vitro from precursor stromal cells. Diabetologia 2008; 51: 155–164.

    CAS  PubMed  Google Scholar 

  12. Seidell JC, Perusse L, Despres JP, Bouchard C . Waist and hip circumferences have independent and opposite effects on cardiovascular disease risk factors: the Quebec family study. Am J Clin Nutr 2001; 74: 315–321.

    CAS  PubMed  Google Scholar 

  13. Terry RB, Stefanick ML, Haskell WL, Wood PD . Contributions of regional adipose tissue depots to plasma lipoprotein concentrations in overweight men and women: possible protective effects of thigh fat. Metabolism 1991; 40: 733–740.

    CAS  PubMed  Google Scholar 

  14. Williams MJ, Hunter GR, Kekes-Szabo T, Snyder S, Treuth MS . Regional fat distribution in women and risk of cardiovascular disease. Am J Clin Nutr 1997; 65: 855–860.

    Article  CAS  PubMed  Google Scholar 

  15. Snijder MB, Visser M, Dekker JM, Goodpaster BH, Harris TB, Kritchevsky SB et al. Low subcutaneous thigh fat is a risk factor for unfavourable glucose and lipid levels, independently of high abdominal fat. The health ABC study. Diabetologia 2005; 48: 301–308.

    CAS  PubMed  Google Scholar 

  16. Buemann B, Astrup A, Pedersen O, Black E, Holst C, Toubro S et al. Possible role of adiponectin and insulin sensitivity in mediating the favorable effects of lower-body fat mass on blood lipids. J Clin Endocrinol Metab 2006; 91: 1698–1704.

    CAS  PubMed  Google Scholar 

  17. Yim JE, Heshka S, Albu JB, Heymsfield S, Gallagher D . Femoral-gluteal subcutaneous and intermuscular adipose tissues have independent and opposing relationships with CVD risk. J Appl Physiol 2008; 104: 700–707.

    PubMed  Google Scholar 

  18. Ferreira I, Snijder MB, Twisk JW, van Mechelen W, Kemper HC, Seidell JC et al. Central fat mass versus peripheral fat and lean mass: opposite (adverse versus favorable) associations with arterial stiffness? The amsterdam growth and health longitudinal study. J Clin Endocrinol Metab 2004; 89: 2632–2639.

    CAS  PubMed  Google Scholar 

  19. Snijder MB, Henry RM, Visser M, Dekker JM, Seidell JC, Ferreira I et al. Regional body composition as a determinant of arterial stiffness in the elderly: the Hoorn Study. J Hypertens 2004; 22: 2339–2347.

    CAS  PubMed  Google Scholar 

  20. Tanko LB, Bagger YZ, Alexandersen P, Larsen PJ, Christiansen C . Peripheral adiposity exhibits an independent dominant antiatherogenic effect in elderly women. Circulation 2003; 107: 1626–1631.

    PubMed  Google Scholar 

  21. Tanko LB, Bagger YZ, Alexandersen P, Larsen PJ, Christiansen C . Central and peripheral fat mass have contrasting effect on the progression of aortic calcification in postmenopausal women. Eur Heart J 2003; 24: 1531–1537.

    PubMed  Google Scholar 

  22. Okura T, Nakata Y, Yamabuki K, Tanaka K . Regional body composition changes exhibit opposing effects on coronary heart disease risk factors. Arterioscler Thromb Vasc Biol 2004; 24: 923–929.

    CAS  PubMed  Google Scholar 

  23. Van Pelt RE, Evans EM, Schechtman KB, Ehsani AA, Kohrt WM . Contributions of total and regional fat mass to risk for cardiovascular disease in older women. Am J Physiol Endocrinol Metab 2002; 282: E1023–E1028.

    CAS  PubMed  Google Scholar 

  24. Snijder MB, Dekker JM, Visser M, Bouter LM, Stehouwer CD, Yudkin JS et al. Trunk fat and leg fat have independent and opposite associations with fasting and postload glucose levels: the Hoorn Study. Diabetes Care 2004; 27: 372–377.

    PubMed  Google Scholar 

  25. Snijder MB, Dekker JM, Visser M, Yudkin JS, Stehouwer CD, Bouter LM et al. Larger thigh and hip circumferences are associated with better glucose tolerance: the Hoorn Study. Obes Res 2003; 11: 104–111.

    PubMed  Google Scholar 

  26. Rocha PM, Barata JT, Teixeira PJ, Ross R, Sardinha LB . Independent and opposite associations of hip and waist circumference with metabolic syndrome components and with inflammatory and atherothrombotic risk factors in overweight and obese women. Metabolism 2008; 57: 1315–1322.

    CAS  PubMed  Google Scholar 

  27. Snijder MB, Zimmet PZ, Visser M, Dekker JM, Seidell JC, Shaw JE . Independent and opposite associations of waist and hip circumferences with diabetes, hypertension and dyslipidemia: the Ausdiab Study. Int J Obes Relat Metab Disord 2004; 28: 402–409.

    CAS  PubMed  Google Scholar 

  28. Canoy D, Boekholdt SM, Wareham N, Luben R, Welch A, Bingham S et al. Body fat distribution and risk of coronary heart disease in men and women in the european prospective investigation into cancer and nutrition in norfolk cohort: a population-based prospective study. Circulation 2007; 116: 2933–2943.

    PubMed  Google Scholar 

  29. Canoy D, Wareham N, Welch A, Bingham S, Luben R, Day N et al. Plasma ascorbic acid concentrations and fat distribution in 19 068 British men and women in the European prospective investigation into cancer and nutrition Norfolk cohort study. Am J Clin Nutr 2005; 82: 1203–1209.

    CAS  PubMed  Google Scholar 

  30. Frayn KN . Adipose tissue as a buffer for daily lipid flux. Diabetologia 2002; 45: 1201–1210.

    CAS  PubMed  Google Scholar 

  31. Pouliot MC, Despres JP, Moorjani S, Lupien PJ, Tremblay A, Nadeau A et al. Regional variation in adipose tissue lipoprotein lipase activity: association with plasma high density lipoprotein levels. Eur J Clin Invest 1991; 21: 398–405.

    Article  CAS  PubMed  Google Scholar 

  32. Bos G, Snijder MB, Nijpels G, Dekker JM, Stehouwer CD, Bouter LM et al. Opposite contributions of trunk and leg fat mass with plasma lipase activities: the Hoorn Study. Obes Res 2005; 13: 1817–1823.

    CAS  PubMed  Google Scholar 

  33. Lemieux I . Energy partitioning in gluteal-femoral fat: does the metabolic fate of triglycerides affect coronary heart disease risk? Arterioscler Thromb Vasc Biol 2004; 24: 795–797.

    CAS  PubMed  Google Scholar 

  34. Frayn KN, Arner P, Yki-Jarvinen H . Fatty acid metabolism in adipose tissue, muscle and liver in health and disease. Essays Biochem 2006; 42: 89–103.

    CAS  PubMed  Google Scholar 

  35. Ruge T, Hodson L, Cheeseman J, Dennis AL, Fielding BA, Humphreys SM et al. Fasted to fed trafficking of fatty acids in human adipose tissue reveals a novel regulatory step for enhanced fat storage. J Clin Endocrinol Metab 2009; 94: 1781–1788.

    CAS  PubMed  Google Scholar 

  36. Dowling HJ, Fried SK, Pi-Sunyer FX . Insulin resistance in adipocytes of obese women: effects of body fat distribution and race. Metabolism 1995; 44: 987–995.

    CAS  PubMed  Google Scholar 

  37. Wahrenberg H, Lonnqvist F, Arner P . Mechanisms underlying regional differences in lipolysis in human adipose tissue. J Clin Invest 1989; 84: 458–467.

    CAS  PubMed  PubMed Central  Google Scholar 

  38. Arner P, Hellstrom L, Wahrenberg H, Bronnegard M . Beta-adrenoceptor expression in human fat cells from different regions. J Clin Invest 1990; 86: 1595–1600.

    CAS  PubMed  PubMed Central  Google Scholar 

  39. Arner P, Lithell H, Wahrenberg H, Bronnegard M . Expression of lipoprotein lipase in different human subcutaneous adipose tissue regions. J Lipid Res 1991; 32: 423–429.

    CAS  PubMed  Google Scholar 

  40. Doolittle MH, Ben-Zeev O, Elovson J, Martin D, Kirchgessner TG . The response of lipoprotein lipase to feeding and fasting. Evidence for posttranslational regulation. J Biol Chem 1990; 265: 4570–4577.

    CAS  PubMed  Google Scholar 

  41. Ramirez ME, McMurry MP, Wiebke GA, Felten KJ, Ren K, Meikle AW et al. Evidence for sex steroid inhibition of lipoprotein lipase in men: comparison of abdominal and femoral adipose tissue. Metabolism 1997; 46: 179–185.

    CAS  PubMed  Google Scholar 

  42. Martin ML, Jensen MD . Effects of body fat distribution on regional lipolysis in obesity. J Clin Invest 1991; 88: 609–613.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Guo Z, Hensrud DD, Johnson CM, Jensen MD . Regional postprandial fatty acid metabolism in different obesity phenotypes. Diabetes 1999; 48: 1586–1592.

    CAS  PubMed  Google Scholar 

  44. Tan GD, Goossens GH, Humphreys SM, Vidal H, Karpe F . Upper and lower-body adipose tissue function: a direct comparison of fat mobilization in humans. Obes Res 2004; 12: 114–118.

    PubMed  Google Scholar 

  45. Gjedsted J, Gormsen LC, Nielsen S, Schmitz O, Djurhuus CB, Keiding S et al. Effects of a 3-day fast on regional lipid and glucose metabolism in human skeletal muscle and adipose tissue. Acta Physiol (Oxf) 2007; 191: 205–216.

    CAS  Google Scholar 

  46. Horowitz JF, Klein S . Whole body and abdominal lipolytic sensitivity to epinephrine is suppressed in upper-body obese women. Am J Physiol Endocrinol Metab 2000; 278: E1144–E1152.

    CAS  PubMed  Google Scholar 

  47. Guo Z, Johnson CM, Jensen MD . Regional lipolytic responses to isoproterenol in women. Am J Physiol 1997; 273 (1 Part 1): E108–E112.

    CAS  PubMed  Google Scholar 

  48. Koutsari C, Snozek CL, Jensen MD . Plasma nefa storage in adipose tissue in the postprandial state: sex-related and regional differences. Diabetologia 2008; 51: 2041–2048.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Romanski SA, Nelson RM, Jensen MD . Meal fatty acid uptake in adipose tissue: gender effects in nonobese humans. Am J Physiol Endocrinol Metab 2000; 279: E455–E462.

    CAS  PubMed  Google Scholar 

  50. Patel JN, Coppack SW, Goldstein DS, Miles JM, Eisenhofer G . Norepinephrine spillover from human adipose tissue before and after a 72-hour fast. J Clin Endocrinol Metab 2002; 87: 3373–3377.

    CAS  PubMed  Google Scholar 

  51. Summers LK, Samra JS, Humphreys SM, Morris RJ, Frayn KN . Subcutaneous abdominal adipose tissue blood flow: variation within and between subjects and relationship to obesity. Clin Sci (Lond) 1996; 91: 679–683.

    CAS  Google Scholar 

  52. Ardilouze JL, Fielding BA, Currie JM, Frayn KN, Karpe F . Nitric oxide and beta-adrenergic stimulation are major regulators of preprandial and postprandial subcutaneous adipose tissue blood flow in humans. Circulation 2004; 109: 47–52.

    CAS  PubMed  Google Scholar 

  53. Karpe F, Fielding BA, Ardilouze JL, Ilic V, Macdonald IA, Frayn KN . Effects of insulin on adipose tissue blood flow in man. J Physiol 2002; 540 (Part 3): 1087–1093.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Kramer FM, Stunkard AJ, Marshall KA, McKinney S, Liebschutz J . Breast-feeding reduces maternal lower-body fat. J Am Diet Assoc 1993; 93: 429–433.

    CAS  PubMed  Google Scholar 

  55. Piche ME, Lapointe A, Weisnagel SJ, Corneau L, Nadeau A, Bergeron J et al. Regional body fat distribution and metabolic profile in postmenopausal women. Metabolism 2008; 57: 1101–1107.

    CAS  PubMed  Google Scholar 

  56. Ley CJ, Lees B, Stevenson JC . Sex- and menopause-associated changes in body-fat distribution. Am J Clin Nutr 1992; 55: 950–954.

    CAS  PubMed  Google Scholar 

  57. Trayhurn P, Rayner DV . Hormones and the ob gene product (leptin) in the control of energy balance. Biochem Soc Trans 1996; 24: 565–570.

    CAS  PubMed  Google Scholar 

  58. Montague CT, Prins JB, Sanders L, Digby JE, O′Rahilly S . Depot- and sex-specific differences in human leptin mrna expression: implications for the control of regional fat distribution. Diabetes 1997; 46: 342–347.

    CAS  PubMed  Google Scholar 

  59. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM . Positional cloning of the mouse obese gene and its human homologue. Nature 1994; 372: 425–432.

    CAS  PubMed  Google Scholar 

  60. 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.

    CAS  PubMed  Google Scholar 

  61. Bluher S, Mantzoros CS . Leptin in humans: lessons from translational research. Am J Clin Nutr 2009; 89: 991S–997S.

    PubMed  PubMed Central  Google Scholar 

  62. Cnop M, Landchild MJ, Vidal J, Havel PJ, Knowles NG, Carr DR et al. The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes 2002; 51: 1005–1015.

    CAS  PubMed  Google Scholar 

  63. Van Harmelen V, Reynisdottir S, Eriksson P, Thorne A, Hoffstedt J, Lonnqvist F et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes 1998; 47: 913–917.

    CAS  PubMed  Google Scholar 

  64. Chaparro J, Reeds DN, Wen W, Xueping E, Klein S, Semenkovich CF et al. Alterations in thigh subcutaneous adipose tissue gene expression in protease inhibitor-based highly active antiretroviral therapy. Metabolism 2005; 54: 561–567.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Papaspyrou-Rao S, Schneider SH, Petersen RN, Fried SK . Dexamethasone increases leptin expression in humans in vivo. J Clin Endocrinol Metab 1997; 82: 1635–1637.

    CAS  PubMed  Google Scholar 

  66. Liuzzi A, Savia G, Tagliaferri M, Lucantoni R, Berselli ME, Petroni ML et al. Serum leptin concentration in moderate and severe obesity: relationship with clinical, anthropometric and metabolic factors. Int J Obes Relat Metab Disord 1999; 23: 1066–1073.

    CAS  PubMed  Google Scholar 

  67. Ho SC, Tai ES, Eng PH, Ramli A, Tan CE, Fok AC . A study in the relationships between leptin, insulin, and body fat in asian subjects. Int J Obes Relat Metab Disord 1999; 23: 246–252.

    CAS  PubMed  Google Scholar 

  68. Vettor R, De Pergola G, Pagano C, Englaro P, Laudadio E, Giorgino F et al. Gender differences in serum leptin in obese people: relationships with testosterone, body fat distribution and insulin sensitivity. Eur J Clin Invest 1997; 27: 1016–1024.

    CAS  PubMed  Google Scholar 

  69. Shimizu H, Shimomura Y, Hayashi R, Ohtani K, Sato N, Futawatari T et al. Serum leptin concentration is associated with total body fat mass, but not abdominal fat distribution. Int J Obes Relat Metab Disord 1997; 21: 536–541.

    CAS  PubMed  Google Scholar 

  70. Saad MF, Damani S, Gingerich RL, Riad-Gabriel MG, Khan A, Boyadjian R et al. Sexual dimorphism in plasma leptin concentration. J Clin Endocrinol Metab 1997; 82: 579–584.

    CAS  PubMed  Google Scholar 

  71. Caprio S, Tamborlane WV, Silver D, Robinson C, Leibel R, McCarthy S et al. Hyperleptinemia: an early sign of juvenile obesity. Relations to body fat depots and insulin concentrations. Am J Physiol 1996; 271 (3 Part 1): E626–E630.

    CAS  PubMed  Google Scholar 

  72. Garnett SP, Hogler W, Blades B, Baur LA, Peat J, Lee J et al. Relation between hormones and body composition, including bone, in prepubertal children. Am J Clin Nutr 2004; 80: 966–972.

    CAS  PubMed  Google Scholar 

  73. Couillard C, Mauriege P, Imbeault P, Prud’homme D, Nadeau A, Tremblay A et al. Hyperleptinemia is more closely associated with adipose cell hypertrophy than with adipose tissue hyperplasia. Int J Obes Relat Metab Disord 2000; 24: 782–788.

    CAS  PubMed  Google Scholar 

  74. Baumgartner RN, Ross RR, Waters DL, Brooks WM, Morley JE, Montoya GD et al. Serum leptin in elderly people: associations with sex hormones, insulin, and adipose tissue volumes. Obes Res 1999; 7: 141–149.

    CAS  PubMed  Google Scholar 

  75. Staiger H, Tschritter O, Machann J, Thamer C, Fritsche A, Maerker E et al. Relationship of serum adiponectin and leptin concentrations with body fat distribution in humans. Obes Res 2003; 11: 368–372.

    CAS  PubMed  Google Scholar 

  76. Rissanen P, Makimattila S, Vehmas T, Taavitsainen M, Rissanen A . Effect of weight loss and regional fat distribution on plasma leptin concentration in obese women. Int J Obes Relat Metab Disord 1999; 23: 645–649.

    CAS  PubMed  Google Scholar 

  77. Bennett FI, McFarlane-Anderson N, Wilks R, Luke A, Cooper RS, Forrester TE . Leptin concentration in women is influenced by regional distribution of adipose tissue. Am J Clin Nutr 1997; 66: 1340–1344.

    CAS  PubMed  Google Scholar 

  78. Lonnqvist F, Wennlund A, Arner P . Relationship between circulating leptin and peripheral fat distribution in obese subjects. Int J Obes Relat Metab Disord 1997; 21: 255–260.

    CAS  PubMed  Google Scholar 

  79. Minocci A, Savia G, Lucantoni R, Berselli ME, Tagliaferri M, Calo G et al. Leptin plasma concentrations are dependent on body fat distribution in obese patients. Int J Obes Relat Metab Disord 2000; 24: 1139–1144.

    CAS  PubMed  Google Scholar 

  80. Nielsen NB, Hojbjerre L, Sonne MP, Alibegovic AC, Vaag A, Dela F et al. Interstitial concentrations of adipokines in subcutaneous abdominal and femoral adipose tissue. Regul Pept 2009; 155: 39–45.

    CAS  PubMed  Google Scholar 

  81. Jensen MD, Moller N, Nair KS, Eisenberg P, Landt M, Klein S . Regional leptin kinetics in humans. Am J Clin Nutr 1999; 69: 18–21.

    CAS  PubMed  Google Scholar 

  82. Perfetto F, Tarquini R, Cornelissen G, Mello G, Tempestini A, Gaudiano P et al. Circadian phase difference of leptin in android versus gynoid obesity. Peptides 2004; 25: 1297–1306.

    CAS  PubMed  Google Scholar 

  83. Langendonk JG, Pijl H, Toornvliet AC, Burggraaf J, Frolich M, Schoemaker RC et al. Circadian rhythm of plasma leptin levels in upper and lower-body obese women: influence of body fat distribution and weight loss. J Clin Endocrinol Metab 1998; 83: 1706–1712.

    CAS  PubMed  Google Scholar 

  84. Fruhbeck G . Intracellular signalling pathways activated by leptin. Biochem J 2006; 393 (Part 1): 7–20.

    CAS  PubMed  Google Scholar 

  85. 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.

    CAS  PubMed  Google Scholar 

  86. 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.

    CAS  PubMed  Google Scholar 

  87. Maeda K, Okubo K, Shimomura I, Funahashi T, Matsuzawa Y, Matsubara K . 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.

    CAS  PubMed  Google Scholar 

  88. Cnop M, Havel PJ, Utzschneider KM, Carr DB, Sinha MK, Boyko EJ et al. Relationship of adiponectin to body fat distribution, insulin sensitivity and plasma lipoproteins: evidence for independent roles of age and sex. Diabetologia 2003; 46: 459–469.

    CAS  PubMed  Google Scholar 

  89. Kern PA, Di Gregorio GB, Lu T, Rassouli N, Ranganathan G . Adiponectin expression from human adipose tissue: relation to obesity, insulin resistance, and tumor necrosis factor-alpha expression. Diabetes 2003; 52: 1779–1785.

    CAS  PubMed  Google Scholar 

  90. Mantzoros CS, Li T, Manson JE, Meigs JB, Hu FB . Circulating adiponectin levels are associated with better glycemic control, more favorable lipid profile, and reduced inflammation in women with type 2 diabetes. J Clin Endocrinol Metab 2005; 90: 4542–4548.

    CAS  PubMed  Google Scholar 

  91. Lara-Castro C, Fu Y, Chung BH, Garvey WT . Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease. Curr Opin Lipidol 2007; 18: 263–270.

    CAS  PubMed  Google Scholar 

  92. Snijder MB, Flyvbjerg A, Stehouwer CD, Frystyk J, Henry RM, Seidell JC et al. Relationship of adiposity with arterial stiffness as mediated by adiponectin in older men and women: the Hoorn Study. Eur J Endocrinol 2009; 160: 387–395.

    CAS  PubMed  Google Scholar 

  93. Buemann B, Sorensen TI, Pedersen O, Black E, Holst C, Toubro S et al. Lower-body fat mass as an independent marker of insulin sensitivity--the role of adiponectin. Int J Obes (Lond) 2005; 29: 624–631.

    CAS  Google Scholar 

  94. Gavrila A, Chan JL, Yiannakouris N, Kontogianni M, Miller LC, Orlova C et al. Serum adiponectin levels are inversely associated with overall and central fat distribution but are not directly regulated by acute fasting or leptin administration in humans: cross-sectional and interventional studies. J Clin Endocrinol Metab 2003; 88: 4823–4831.

    CAS  PubMed  Google Scholar 

  95. Hanley AJ, Bowden D, Wagenknecht LE, Balasubramanyam A, Langfeld C, Saad MF et al. Associations of adiponectin with body fat distribution and insulin sensitivity in nondiabetic Hispanics and African-Americans. J Clin Endocrinol Metab 2007; 92: 2665–2671.

    CAS  PubMed  Google Scholar 

  96. Vilarrasa N, Vendrell J, Maravall J, Broch M, Estepa A, Megia A et al. Distribution and determinants of adiponectin, resistin and ghrelin in a randomly selected healthy population. Clin Endocrinol (Oxf) 2005; 63: 329–335.

    CAS  Google Scholar 

  97. Park KG, Park KS, Kim MJ, Kim HS, Suh YS, Ahn JD et al. Relationship between serum adiponectin and leptin concentrations and body fat distribution. Diabetes Res Clin Pract 2004; 63: 135–142.

    CAS  PubMed  Google Scholar 

  98. Fisher FM, McTernan PG, Valsamakis G, Chetty R, Harte AL, Anwar AJ et al. Differences in adiponectin protein expression: effect of fat depots and type 2 diabetic status. Horm Metab Res 2002; 34: 650–654.

    CAS  PubMed  Google Scholar 

  99. Drolet R, Belanger C, Fortier M, Huot C, Mailloux J, Legare D et al. Fat depot-specific impact of visceral obesity on adipocyte adiponectin release in women. Obesity (Silver Spring) 2009; 17: 424–430.

    CAS  Google Scholar 

  100. Rasmussen MS, Lihn AS, Pedersen SB, Bruun JM, Rasmussen M, Richelsen B . Adiponectin receptors in human adipose tissue: effects of obesity, weight loss, and fat depots. Obesity (Silver Spring) 2006; 14: 28–35.

    CAS  Google Scholar 

  101. Kriegler M, Perez C, DeFay K, Albert I, Lu SD . A novel form of TNF/cachectin is a cell surface cytotoxic transmembrane protein: ramifications for the complex physiology of TNF. Cell 1988; 53: 45–53.

    CAS  PubMed  Google Scholar 

  102. Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF et al. A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 1997; 385: 729–733.

    CAS  PubMed  Google Scholar 

  103. Fain JN, Bahouth SW, Madan AK . Tnfalpha release by the nonfat cells of human adipose tissue. Int J Obes Relat Metab Disord 2004; 28: 616–622.

    CAS  PubMed  Google Scholar 

  104. Langin D, Arner P . Importance of TNFalpha and neutral lipases in human adipose tissue lipolysis. Trends Endocrinol Metab 2006; 17: 314–320.

    CAS  PubMed  Google Scholar 

  105. Hotamisligil GS, Shargill NS, Spiegelman BM . Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993; 259: 87–91.

    CAS  PubMed  Google Scholar 

  106. Plomgaard P, Nielsen AR, Fischer CP, Mortensen OH, Broholm C, Penkowa M et al. Associations between insulin resistance and TNF-αalpha in plasma, skeletal muscle and adipose tissue in humans with and without type 2 diabetes. Diabetologia 2007; 50: 2562–2571.

    CAS  PubMed  Google Scholar 

  107. Uysal KT, Wiesbrock SM, Marino MW, Hotamisligil GS . Protection from obesity-induced insulin resistance in mice lacking TNF-αlpha function. Nature 1997; 389: 610–614.

    CAS  PubMed  Google Scholar 

  108. Carey AL, Bruce CR, Sacchetti M, Anderson MJ, Olsen DB, Saltin B et al. Interleukin-6 and tumor necrosis factor-alpha are not increased in patients with type 2 diabetes: evidence that plasma interleukin-6 is related to fat mass and not insulin responsiveness. Diabetologia 2004; 47: 1029–1037.

    CAS  PubMed  Google Scholar 

  109. Zahorska-Markiewicz B, Janowska J, Olszanecka-Glinianowicz M, Zurakowski A . Serum concentrations of TNF-αalpha and soluble TNF-αalpha receptors in obesity. Int J Obes Relat Metab Disord 2000; 24: 1392–1395.

    CAS  PubMed  Google Scholar 

  110. Katsuki A, Sumida Y, Murashima S, Murata K, Takarada Y, Ito K et al. Serum levels of tumor necrosis factor-alpha are increased in obese patients with noninsulin-dependent diabetes mellitus. J Clin Endocrinol Metab 1998; 83: 859–862.

    CAS  PubMed  Google Scholar 

  111. Mohamed-Ali V, Goodrick S, Rawesh A, Katz DR, Miles JM, Yudkin JS et al. Subcutaneous adipose tissue releases interleukin-6, but not tumor necrosis factor-alpha, in vivo. J Clin Endocrinol Metab 1997; 82: 4196–4200.

    CAS  PubMed  Google Scholar 

  112. Mohamed-Ali V, Goodrick S, Bulmer K, Holly JM, Yudkin JS, Coppack SW . Production of soluble tumor necrosis factor receptors by human subcutaneous adipose tissue in vivo. Am J Physiol 1999; 277 (6 Part 1): E971–E975.

    CAS  PubMed  Google Scholar 

  113. Perry CD, Alekel DL, Ritland LM, Bhupathiraju SN, Stewart JW, Hanson LN et al. Centrally located body fat is related to inflammatory markers in healthy postmenopausal women. Menopause 2008; 15 (4 Part 1): 619–627.

    PubMed  PubMed Central  Google Scholar 

  114. Good M, Newell FM, Haupt LM, Whitehead JP, Hutley LJ, Prins JB . TNF and TNF receptor expression and insulin sensitivity in human omental and subcutaneous adipose tissue--influence of BMI and adipose distribution. Diab Vasc Dis Res 2006; 3: 26–33.

    PubMed  Google Scholar 

  115. Hauner H, Bender M, Haastert B, Hube F . Plasma concentrations of soluble TNF-αalpha receptors in obese subjects. Int J Obes Relat Metab Disord 1998; 22: 1239–1243.

    CAS  PubMed  Google Scholar 

  116. Kamimura D, Ishihara K, Hirano T . Il-6 signal transduction and its physiological roles: the signal orchestration model. Rev Physiol Biochem Pharmacol 2003; 149: 1–38.

    CAS  PubMed  Google Scholar 

  117. Fain JN, Madan AK, Hiler ML, Cheema P, Bahouth SW . 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.

    CAS  PubMed  Google Scholar 

  118. Kern PA, Ranganathan S, Li CL, Wood L, Ranganathan G . Adipose tissue tumor necrosis factor and interleukin-6 expression in human obesity and insulin resistance. Am J Physiol-Endocrinol Metab 2001; 280: E745–E751.

    CAS  PubMed  Google Scholar 

  119. Beasley LE, Koster A, Newman AB, Javaid MK, Ferrucci L, Kritchevsky SB et al. Inflammation and race and gender differences in computerized tomography-measured adipose depots. Obesity (Silver Spring) 2009; 17: 1062–1069.

    Google Scholar 

  120. Hoene M, Weigert C . The role of interleukin-6 in insulin resistance, body fat distribution and energy balance. Obes Rev 2008; 9: 20–29.

    CAS  PubMed  Google Scholar 

  121. Yang Q, Graham TE, Mody N, Preitner F, Peroni OD, Zabolotny JM et al. Serum retinol binding protein 4 contributes to insulin resistance in obesity and type 2 diabetes. Nature 2005; 436: 356–362.

    CAS  PubMed  Google Scholar 

  122. Gavi S, Stuart LM, Kelly P, Melendez MM, Mynarcik DC, Gelato MC et al. Retinol-binding protein 4 is associated with insulin resistance and body fat distribution in nonobese subjects without type 2 diabetes. J Clin Endocrinol Metab 2007; 92: 1886–1890.

    CAS  PubMed  Google Scholar 

  123. Gavi S, Qurashi S, Stuart LM, Lau R, Melendez MM, Mynarcik DC et al. Influence of age on the association of retinol-binding protein 4 with metabolic syndrome. Obesity (Silver Spring) 2008; 16: 893–895.

    CAS  Google Scholar 

  124. Youn BS, Kloting N, Kratzsch J, Lee N, Park JW, Song ES et al. Serum vaspin concentrations in human obesity and type 2 diabetes. Diabetes 2008; 57: 372–377.

    CAS  PubMed  Google Scholar 

  125. Macfarlane DP, Forbes S, Walker BR . Glucocorticoids and fatty acid metabolism in humans: fuelling fat redistribution in the metabolic syndrome. J Endocrinol 2008; 197: 189–204.

    CAS  PubMed  Google Scholar 

  126. Burt MG, Gibney J, Ho KK . Characterization of the metabolic phenotypes of Cushing's syndrome and growth hormone deficiency: a study of body composition and energy metabolism. Clin Endocrinol (Oxf) 2006; 64: 436–443.

    Google Scholar 

  127. Rebuffe-Scrive M, Krotkiewski M, Elfverson J, Bjorntorp P . Muscle and adipose tissue morphology and metabolism in Cushing's syndrome. J Clin Endocrinol Metab 1988; 67: 1122–1128.

    CAS  PubMed  Google Scholar 

  128. Samra JS, Clark ML, Humphreys SM, MacDonald IA, Bannister PA, Frayn KN . Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue. J Clin Endocrinol Metab 1998; 83: 626–631.

    CAS  PubMed  Google Scholar 

  129. Mayo-Smith W, Hayes CW, Biller BM, Klibanski A, Rosenthal H, Rosenthal DI . Body fat distribution measured with ct: correlations in healthy subjects, patients with anorexia nervosa, and patients with Cushing syndrome. Radiology 1989; 170: 515–518.

    CAS  PubMed  Google Scholar 

  130. Wajchenberg BL, Bosco A, Marone MM, Levin S, Rocha M, Lerario AC et al. Estimation of body fat and lean tissue distribution by dual energy X-ray absorptiometry and abdominal body fat evaluation by computed tomography in cushing′s disease. J Clin Endocrinol Metab 1995; 80: 2791–2794.

    CAS  PubMed  Google Scholar 

  131. Rockall AG, Sohaib SA, Evans D, Kaltsas G, Isidori AM, Monson JP et al. Computed tomography assessment of fat distribution in male and female patients with Cushing's syndrome. Eur J Endocrinol 2003; 149: 561–567.

    CAS  PubMed  Google Scholar 

  132. Friedman TC, Mastorakos G, Newman TD, Mullen NM, Horton EG, Costello R et al. Carbohydrate and lipid metabolism in endogenous hypercortisolism: shared features with metabolic syndrome x and niddm. Endocr J 1996; 43: 645–655.

    CAS  PubMed  Google Scholar 

  133. Walker BR . Cortisol--cause and cure for metabolic syndrome? Diabet Med 2006; 23: 1281–1288.

    CAS  PubMed  Google Scholar 

  134. Garg A . Acquired and inherited lipodystrophies. N Engl J Med 2004; 350: 1220–1234.

    CAS  PubMed  Google Scholar 

  135. Garg A, Peshock RM, Fleckenstein JL . Adipose tissue distribution pattern in patients with familial partial lipodystrophy (Dunnigan variety). J Clin Endocrinol Metab 1999; 84: 170–174.

    CAS  PubMed  Google Scholar 

  136. Schmidt HH, Genschel J, Baier P, Schmidt M, Ockenga J, Tietge UJ et al. Dyslipemia in familial partial lipodystrophy caused by an r482w mutation in the lmna gene. J Clin Endocrinol Metab 2001; 86: 2289–2295.

    CAS  PubMed  Google Scholar 

  137. Barroso I, Gurnell M, Crowley VE, Agostini M, Schwabe JW, Soos MA et al. Dominant negative mutations in human ppargamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 1999; 402: 880–883.

    CAS  PubMed  Google Scholar 

  138. Savage DB, Tan GD, Acerini CL, Jebb SA, Agostini M, Gurnell M et al. Human metabolic syndrome resulting from dominant-negative mutations in the nuclear receptor peroxisome proliferator-activated receptor-gamma. Diabetes 2003; 52: 910–917.

    CAS  PubMed  Google Scholar 

  139. Misra A, Peethambaram A, Garg A . Clinical features and metabolic and autoimmune derangements in acquired partial lipodystrophy: report of 35 cases and review of the literature. Medicine (Baltimore) 2004; 83: 18–34.

    CAS  Google Scholar 

  140. Lindgren CM, Heid IM, Randall JC, Lamina C, Steinthorsdottir V, Qi L et al. Genome-wide association scan meta-analysis identifies three loci influencing adiposity and fat distribution. PLoS Genet 2009; 5: e1000508.

    PubMed  PubMed Central  Google Scholar 

  141. Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K et al. Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 2002; 87: 2784–2791.

    CAS  PubMed  Google Scholar 

  142. Akazawa S, Sun F, Ito M, Kawasaki E, Eguchi K . Efficacy of troglitazone on body fat distribution in type 2 diabetes. Diabetes Care 2000; 23: 1067–1071.

    CAS  PubMed  Google Scholar 

  143. Albu JB, Kenya S, He Q, Wainwright M, Berk ES, Heshka S et al. Independent associations of insulin resistance with high whole-body intermuscular and low leg subcutaneous adipose tissue distribution in obese hiv-infected women. Am J Clin Nutr 2007; 86: 100–106.

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank the Wellcome Trust for support of our work.

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  1. Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK

    K N Manolopoulos, F Karpe & K N Frayn

  2. NIHR Oxford Biomedical Research Centre, ORH Trust, OCDEM, Churchill Hospital, Oxford, UK

    F Karpe

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Manolopoulos, K., Karpe, F. & Frayn, K. Gluteofemoral body fat as a determinant of metabolic health. Int J Obes 34, 949–959 (2010). https://doi.org/10.1038/ijo.2009.286

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