Rolle von endokrinen und metabolischen Faktoren des Fettgewebes in der Pathophysiologie des metabolischen Syndroms

  • Antje Böttner
  • Jürgen Kratzsch
  • Annette G. Beck-Sickinger
  • Michael Stumvoll
  • Wieland Kiess
Part of the Molekulare Medizin book series (MOLMED)


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

4.1.6 Literatur

  1. Ahima RS, Flier JS (2000) Adipose tissue as an endocrine organ. Trends Endocrinol Metab 11: 327–332PubMedGoogle Scholar
  2. Ahima RS, Prabakaran D, Mantzoros C, Qu D, Lowell B, Maratos-Flier E, Flier JS (1996) Role of leptin in the neuroendocrine response to fasting. Nature 382: 250–252PubMedGoogle Scholar
  3. Ahima RS, Saper CB, Flier JS, Elmquist JK (2000) Leptin regulation of neuroendocrine systems. Front Neuroendocrinol 21: 263–307PubMedGoogle Scholar
  4. Ailhaud G, Grimaldi P, Negrel R (1992) Cellular and molecular aspects of adipose tissue development. Annu Rev Nutr 12: 207–233PubMedGoogle Scholar
  5. Allison DB, Kaprio J, Korkeila M, Koskenvuo M, Neale MC, Hayakawa K (1996) The heritability of body mass index among an international sample of monozygotic twins reared apart. Int J Obes Relat Metab Disord 20: 501–506PubMedGoogle Scholar
  6. Allison DB, Fontaine KR, Manson JE, Stevens J, VanItallie TB (1999) Annual deaths attributable to obesity in the United States. JAMA 282: 1530–1538PubMedGoogle Scholar
  7. Barroso I, Gurnell M, Crowley VE et al. (1999) Dominant negative mutations in human PPARgamma associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402: 880–883PubMedGoogle Scholar
  8. Belanger C, Luu-The V, Dupont P, Tchernof A (2002) Adipose tissue intracrinology: potential importance of local androgen/estrogen metabolism in the regulation of adiposity. Horm Metab Res 34: 737–745PubMedGoogle Scholar
  9. Bennett BD, Solar GP, Yuan JQ, Mathias J, Thomas GR, Matthews W (1996) A role for leptin and its cognate receptor in hematopoiesis. Curr Biol 6: 1170–1180PubMedGoogle Scholar
  10. Berg AH, Combs TP, Du X, Brownlee M, Scherer PE (2001) The adipocyte-secreted protein Acrp30 enhances hepatic insulin action. Nat Med 7: 947–953PubMedGoogle Scholar
  11. Boney CM, Moats-Staats BM, Stiles AD, D’Ercole AJ (1994) Expression of insulin-like growth factor-I (IGF-I) and IGF-binding proteins during adipogenesis. Endocrinology 135: 1863–1868PubMedGoogle Scholar
  12. Böttner A, Kratzsch J, Müller G et al. (2004) Gender differences of adiponectin levels develop during the progression of puberty and are related to serum androgen levels. J Clin Endocrinol Metab 89: 4053–4061PubMedGoogle Scholar
  13. Bouloumie A, Drexler HC, Lafontan M, Busse R (1998) Leptin, the product of ob gene, promotes angiogenesis. Circ Res 83: 1059–1066PubMedGoogle Scholar
  14. Bouret SG, Draper SJ, Simerly RB (2004) Trophic action of leptin on hypothalamic neurons that regulate feeding. Science 304: 108–110PubMedGoogle Scholar
  15. Broadway NM, Saggerson ED (1997) Effect of membrane environment on the activity and inhibitability by malonyl-CoA of the carnitine acyltransferase of hepatic microsomal membranes. Biochem J 322: 435–440PubMedGoogle Scholar
  16. Bulun SE, Simpson ER (1994) Competitive reverse transcription-polymerase chain reaction analysis indicates that levels of aromatase cytochrome P450 transcripts in adipose tissue of buttocks, thighs, and abdomen of women increase with advancing age. J Clin Endocrinol Metab 78: 428–432PubMedGoogle Scholar
  17. Burt DW, Boswell JM, Paton IR, Butterwith SC (1992) Multiple growth factor mRNAs are expressed in chicken adipocyte precursor cells. Biochem Biophys Res Commun 187: 1298–1305PubMedGoogle Scholar
  18. Campfield LA, Smith FJ, Burn P (1996) The ob protein (leptin) pathway — a link between adipose tissue mass and central neural networks. Horm Metab Res 28: 619–632PubMedGoogle Scholar
  19. Cassis LA, English VL, Bharadwaj K, Boustany CM (2004) Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes. Endocrinology 145: 169–174PubMedGoogle Scholar
  20. Cawthorne MA, Morton NM, Pallett AL, Liu YL, Emilsson V (1998) Peripheral metabolic actions of leptin. Proc Nutr Soc 57: 449–453PubMedGoogle Scholar
  21. Chandran M, Phillips SA, Ciaraldi T, Henry RR (2003) Adiponectin: more than just another fat cell hormone? Diabetes Care 26: 2442–2450PubMedGoogle Scholar
  22. Chen H, Charlat O, Tartaglia LA et al. (1996) Evidence that the diabetes gene encodes the leptin receptor: Identification of a mutation in the leptin receptor gene in db/db mice. Cell 84: 491–495PubMedGoogle Scholar
  23. Chua SC Jr, Chung WK, Wu-Peng XS, Zhang Y, Liu SM, Tartaglia L, Leibel RL (1996) Phenotypes of mouse diabetes and rat fatty due to mutations in the OB (leptin) receptor. Science 271: 994–996PubMedGoogle Scholar
  24. Cianflone K, Maslowska M, Sniderman AD (1999) Acylation stimulating protein (ASP), an adipocyte autocrine: new directions. Semin Cell Dev Biol 10: 31–41PubMedGoogle Scholar
  25. Clarke SD (2001) Polyunsaturated fatty acid regulation of gene transcription: a molecular mechanism to improve the metabolic syndrome. J Nutr 131: 1129–1132PubMedGoogle Scholar
  26. Clarke SD, Nelson C, Gaperikova D, deMar J, Lapillonne A, and Heird WC (2003) Fatty acid regulation of gene expression: A genomic mechanism to improve the metabolic syndrome. In: Bachmann C, Koletzko B (eds) Genetic expression and nutrition. Vevey/Lippincott Williams & Wilkins Philadelphia, pp 67–83Google Scholar
  27. Clement K, Vaisse C, Lahlou N et al. (1998) A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 392: 398–401PubMedGoogle Scholar
  28. Clement K, Boutin P, Froguel P (2002) Genetics of obesity. Am J Pharmacogenomics 2: 177–187PubMedGoogle Scholar
  29. Cohen P, Friedman JM (2004) Leptin and the control of metabolism: Role for stearoyl-CoA desaturase-1 (SCD-1). J Nutr 134: 2455S–2463SPubMedGoogle Scholar
  30. Considine RV (2001) Regulation of leptin production. Rev Endocr Metab Disord 2: 357–363PubMedGoogle Scholar
  31. Considine RV, Nyce MR, Morales LM et al. (1996a) Paracrine stimulation of preadipocyte-enriched cell cultures by mature adipocytes. Am J Physiol 270: E895–E899PubMedGoogle Scholar
  32. Considine RV, Sinha MK, Heiman ML et al. (1996b) Serum immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med 334: 292–295PubMedGoogle Scholar
  33. Cottam R (2004) Obesity and culture. Lancet 364: 1202–1203PubMedGoogle Scholar
  34. Dalgaard LT, Pedersen O (2001) Uncoupling proteins: Functional characteristics and role in the pathogenesis of obesity and type II diabetes. Diabetologia 44: 946–965PubMedGoogle Scholar
  35. Darimont C, Delansorne R, Paris J, Ailhaud G, Negrel R (1997) Influence of estrogenic status on the lipolytic activity of parametrial adipose tissue in vivo: An in situ microdialysis study. Endocrinology 138: 1092–1096PubMedGoogle Scholar
  36. Del Prato S, Bonadonna RC, Bonora E, Gulli G, Solini A, Shank M, DeFronzo RA (1993) Characterization of cellular defects of insulin action in type 2 (non-insulin-dependent) diabetes mellitus. J Clin Invest 91: 484–494PubMedGoogle Scholar
  37. Deslypere JP, Verdonck L, Vermeulen A (1985) Fat tissue: A steroid reservoir and site of steroid metabolism. J Clin Endocrinol Metab 61: 564–570PubMedGoogle Scholar
  38. Dietze D, Koenen M, Rohrig K, Horikoshi H, Hauner H, Eckel J (2002) Impairment of insulin signaling in human skeletal muscle cells by co-culture with human adipocytes. Diabetes 51: 2369–2376PubMedGoogle Scholar
  39. Dötsch J, Rascher W, Meissner U (2004) Perinatal programming of appetite control by leptin? Eur J Endocrinol 151: 159–160Google Scholar
  40. Ehrhart-Bornstein M, Lamounier-Zepter V, Schraven A et al. (2003) Human adipocytes secrete mineralocorticoid-releasing factors. Proc Natl Acad Sci USA 100: 14211–14216PubMedGoogle Scholar
  41. Engeli S, Schling P, Gorzelniak K et al. (2003) The adipose-tissue renin-angiotensin-aldosterone system: role in the metabolic syndrome? Int J Biochem Cell Biol 35: 807–825PubMedGoogle Scholar
  42. Entenmann G, Hauner H (1996) Relationship between replication and differentiation in cultured human adipocyte precursor cells. Am J Physiol 270: C1011–C1016PubMedGoogle Scholar
  43. Evans RM, Barish GD, Wang YX (2004) PPARs and the complex journey to obesity. Nat Med 10: 355–361PubMedGoogle Scholar
  44. Farooqi IS, Jebb SA, Langmack G et al. (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341: 879–884PubMedGoogle Scholar
  45. Fischer-Posovszky P, Tornqvist H, Debatin KM, Wabitsch M (2004) Inhibition of death-receptor mediated apoptosis in human adipocytes by the insulin-like growth factor I (IGF-I)/IGF-I receptor autocrine circuit. Endocrinology 145: 1849–1859PubMedGoogle Scholar
  46. Flier JS (1998) Whats in a name? In search of leptins physiological role. J Clin Endocrinol Metab 83: 1407–1413PubMedGoogle Scholar
  47. Flier JS (2004) Obesity wars: molecular progress confronts an expanding epidemic. Cell 116: 337–350PubMedGoogle Scholar
  48. Folkerd EJ, James VH (1982) Studies on the activity of 17 beta-hydroxysteroid dehydrogenase in human adipose tissue. J Steroid Biochem 16: 539–543PubMedGoogle Scholar
  49. Friedman JM (1998) Leptin, leptin receptors, and the control of body weight. Nutr Rev 56: S38–S46PubMedGoogle Scholar
  50. Friedman JM (2003) A war on obesity, not the obese. Science 299: 856–858PubMedGoogle Scholar
  51. Friedman JM (2004) Modern science versus the stigma of obesity. Nat Med 10: 563–569PubMedGoogle Scholar
  52. Friedman JM, Halaas JL (1998) Leptin and the regulation of body weight in mammals. Nature 395: 763–770PubMedGoogle Scholar
  53. Fruebis J, Tsao TS, Javorschi S et al. (2001) Proteolytic cleavage product of 30-kDa adipocyte complement-related protein increases fatty acid oxidation in muscle and causes weight loss in mice. Proc Natl Acad Sci USA 98: 2005–2010PubMedGoogle Scholar
  54. Frühbeck G, Aguado M, Martínez A (1997) In vitro lipolytic effect of leptin on mouse adipocytes: Evidence for a possible autocrine/paracrine role of leptin. Biochem Biophys Res Commun 240: 590–594PubMedGoogle Scholar
  55. Fryer LG, Parbu-Patel A, Carling D (2002) The anti-diabetic drugs rosiglitazone and metformin stimulate AMP-activated protein kinase through distinct signaling pathways. J Biol Chem 277: 25226–25232PubMedGoogle Scholar
  56. Gil-Campos M, Canete RR, Gil A (2004) Adiponectin, the missing link in insulin resistance and obesity. Clin Nutr 23: 963–974PubMedGoogle Scholar
  57. Glasow A, Haidan A, Hilbers U et al. (1998) Expression of Ob receptor in normal human adrenals: differential regulation of adrenocortical and adrenomedullary function by leptin. J Clin Endocrinol Metab 83: 4459–4466PubMedGoogle Scholar
  58. Glatz JF, Storch J (2001) Unravelling the significance of cellular fatty acid-binding proteins. Curr Opin Lipidol 12: 267–274PubMedGoogle Scholar
  59. Goldstein BJ, Scalia R (2004) Adiponectin: A novel adipokine linking adipocytes and vascular function. J Clin Endocrinol Metab 89: 2563–2568PubMedGoogle Scholar
  60. Gregoire FM (2001) Adipocyte differentiation: from fibroblast to endocrine cell. Exp Biol Med (Maywood) 226: 997–1002Google Scholar
  61. Gregoire FM, Smas CM, Sul HS (1998) Understanding adipocyte differentiation. Physiol Rev 78: 783–809PubMedGoogle Scholar
  62. Groop L (2000) Genetics of the metabolic syndrome. Br J Nutr 83Suppl 1:S39–48PubMedGoogle Scholar
  63. Halaas JL, Gajiwala KS, Maffei M et al. (1995) Weight-reducing effects of the plasma protein encoded by the obese gene. Science 269: 543–546PubMedGoogle Scholar
  64. Hansen FM, Fahmy N, Nielsen JH (1980) The influence of sexual hormones on lipogenesis and lipolysis in rat fat cells. Acta Endocrinol (Copenh) 95: 566–570PubMedGoogle Scholar
  65. Hardardottir I, Grunfeld C, Feingold KR (1994) Effects of endotoxin and cytokines on lipid metabolism. Curr Opin Lipidol 5: 207–215PubMedGoogle Scholar
  66. Hardie DG (2003) Minireview: the AMP-activated protein kinase cascade: the key sensor of cellular energy status. Endocrinology 144: 5179–5183PubMedGoogle Scholar
  67. Hauner H, Wabitsch M (2004) Das Fettgewebe als endokrines Organ. In: Wabitsch M, Hebebrand J, Kiess W, Zwiauer K (Hrsg) Adipositas bei Kindern und Jugendlichen. Springer, Berlin Heidelberg New York, S 147–156Google Scholar
  68. Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ (2001) The biology of white adipocyte proliferation. Obes Rev 2: 239–254PubMedGoogle Scholar
  69. Havel PJ (2002) Control of energy homeostasis and insulin action by adipocyte hormones: leptin, acylation stimulating protein, and adiponectin. Curr Opin Lipidol 13: 51–59PubMedGoogle Scholar
  70. Havel PJ (2004) Update on adipocyte hormones: regulation of energy balance and carbohydrate/lipid metabolism. Diabetes 53Suppl 1: S143–S151PubMedGoogle Scholar
  71. Hebebrand J, Sommerlad C, Geller F, Gorg T, Hinney A (2001) The genetics of obesity: practical implications. Int J Obes Relat Metab Disord 25Suppl 1: S10–S18PubMedGoogle Scholar
  72. Heymsfield SB, Greenberg AS, Fujioka K et al. (1999) Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 282: 1568–1575PubMedGoogle Scholar
  73. Himms-Hagen J (1999) Physiological roles of the leptin endocrine system: differences between mice and humans. Crit Rev Clin Lab Sci 36: 575–655PubMedGoogle Scholar
  74. Hinney A, Hohmann S, Geller F et al. (2003) Melanocortin-4 receptor gene: case-control study and transmission disequilibrium test confirm that functionally relevant mutations are compatible with a major gene effect for extreme obesity. J Clin Endocrinol Metab 88: 4258–4267PubMedGoogle Scholar
  75. Hirsch J, Knittle JL (1970) Cellularity of obese and nonobese human adipose tissue. Fed Proc 29: 1516–1521PubMedGoogle Scholar
  76. Hoggard N, Mercer JG, Rayner DV, Moar K, Trayhurn P, Williams LM (1997) Localization of leptin receptor mRNA splice variants in murine peripheral tissues by RT-PCR and in situ hybridization. Biochem Biophys Res Commun 232: 383–387PubMedGoogle Scholar
  77. Holcomb IN, Kabakoff RC, Chan B et al. (2000) FIZZ1, a novel cysteine-rich secreted protein associated with pulmonary inflammation, defines a new gene family. EMBO J 19: 4046–4055PubMedGoogle Scholar
  78. Hotamisligil GS, Spiegelman BM (1994) Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 43: 1271–1278PubMedGoogle Scholar
  79. Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 259: 87–91PubMedGoogle Scholar
  80. Hotamisligil GS, Arner P, Caro JF, Atkinson RL, Spiegelman BM (1995) Increased adipose tissue expression of tumor necrosis factor-alpha in human obesity and insulin resistance. J Clin Invest 95: 2409–2415PubMedGoogle Scholar
  81. Hotta K, Funahashi T, Arita Y et al. (2000) Plasma concentrations of a novel, adipose-specific protein, adiponectin, in type 2 diabetic patients. Arterioscler Thromb Vasc Biol 20: 1595–1599PubMedGoogle Scholar
  82. Housknecht KL, Baile CA, Matteri RL, Spurlock ME (1998) The biology of leptin: A review. J Anim Sci 76: 1405–1420Google Scholar
  83. Hu E, Liang P, Spiegelman BM (1996) AdipoQ is a novel adipose-specific gene dysregulated in obesity. J Biol Chem 271: 10697–10703PubMedGoogle Scholar
  84. Hu FB, Manson JE, Stampfer MJ, Colditz G, Liu S, Solomon CG, Willett WC (2001) Diet, lifestyle, and the risk of type 2 diabetes mellitus in women. N Engl J Med 345: 790–797PubMedGoogle Scholar
  85. Hube F, Hauner H (1999) The role of TNF-alpha in human adipose tissue: prevention of weight gain at the expense of insulin resistance? Horm Metab Res 31: 626–631PubMedGoogle Scholar
  86. Hube F, Birgel M, Lee YM, Hauner H (1999) Expression pattern of tumour necrosis factor receptors in subcutaneous and omental human adipose tissue: role of obesity and non-insulin-dependent diabetes mellitus. Eur J Clin Invest 29: 672–678PubMedGoogle Scholar
  87. Iglesias MA, Ye JM, Frangioudakis G et al. (2002) AICAR administration causes an apparent enhancement of muscle and liver insulin action in insulin-resistant high-fat-fed rats. Diabetes 51: 2886–2894PubMedGoogle Scholar
  88. Ioffe E, Moon B, Connolly E, Friedman JM (1998) Abnormal regulation of the leptin gene in the pathogenesis of obesity. Proc Natl Acad Sci USA 95: 11852–11857PubMedGoogle Scholar
  89. Jackson RS, Creemers JW, Ohagi S et al. (1997) Obesity and impaired prohormone processing associated with mutations in the human prohormone convertase 1 gene. Nat Genet 16: 303–306PubMedGoogle Scholar
  90. Juhan-Vague I, Alessi MC, Mavri A, Morange PE (2003) Plasminogen activator inhibitor-1, inflammation, obesity, insulin resistance and vascular risk. J Thromb Haemost 1: 1575–1579PubMedGoogle Scholar
  91. Kalant D, Cain SA, Maslowska M, Sniderman AD, Cianflone K, Monk PN (2003) The chemoattractant receptor-like protein C5L2 binds the C3a des-Arg77/acylation-stimulating protein. J Biol Chem 278: 11123–11129PubMedGoogle Scholar
  92. Kawanami D, Maemura K, Takeda N et al. (2004) Direct reciprocal effects of resistin and adiponectin on vascular endothelial cells: a new insight into adipocytokine-endothelial cell interactions. Biochem Biophys Res Commun 314: 415–419PubMedGoogle Scholar
  93. Kemp BE, Stapleton D, Campbell DJ et al. (2003) AMP-activated protein kinase, super metabolic regulator. Biochem Soc Trans 31: 162–168PubMedGoogle Scholar
  94. Kershaw EE, Flier JS (2004) Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 89: 2548–2556PubMedGoogle Scholar
  95. Kiess W, Blum WF, Aubert ML (1998) Leptin, puberty and reproductive function: lessons from animal studies and observations in humans. Eur J Endocrinol 138: 26–29PubMedGoogle Scholar
  96. Kim KH, Lee K, Moon YS, Sul HS (2001) A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J Biol Chem 276: 11252–11256PubMedGoogle Scholar
  97. Kishi K, Yuasa T, Minami A et al. (2000) AMP-Activated protein kinase is activated by the stimulations of G(q)-coupled receptors. Biochem Biophys Res Commun 276: 16–22PubMedGoogle Scholar
  98. Kissebah AH, Krakower GR (1994) Regional adiposity and morbidity. Physiol Rev 74: 761–811PubMedGoogle Scholar
  99. Knittle JL, Timmers K, Ginsberg-Fellner F, Brown RE, Katz DP (1979) The growth of adipose tissue in children and adolescents. Cross-sectional and longitudinal studies of adipose cell number and size. J Clin Invest 63: 239–246PubMedGoogle Scholar
  100. Körner A, Wabitsch M, Seidel B et al. (2005) Adiponectin expression in humans is dependent on differentiation of adipocytes and down-regulated by humoral serum components of high molecular weight. Biochem Biophys Res Commun 337: 540–550PubMedGoogle Scholar
  101. Kratzsch J, Deimel A, Galler A, Kapellen T, Klinghammer A, Kiess W (2004) Increased serum soluble leptin receptor levels in children and adolescents with type 1 diabetes mellitus. Eur J Endocrinol 151: 475–481PubMedGoogle Scholar
  102. Kratzsch J, Schubring C, Stitzel B, Böttner A, Berthold A, Thiery J, Kiess W (2005) Inverse changes in the serum levels of the soluble leptin receptor and leptin in neonates: relations to anthropometric data. J Clin Endocrinol Metab 90: 2212–2217PubMedGoogle Scholar
  103. Krude H, Biebermann H, Luck W, Horn R, Brabant G, Gruters A (1998) Severe early-onset obesity, adrenal insufficiency and red hair pigmentation caused by POMC mutations in humans. Nat Genet 19: 155–157PubMedGoogle Scholar
  104. Kubota N, Terauchi Y, Yamauchi T et al. (2002) Disruption of adiponectin causes insulin resistance and neointimal formation. J Biol Chem 19(277): 25863–25866Google Scholar
  105. Lammert A, Kiess W, Böttner A, Glasow A, Kratzsch J (2001) Soluble leptin receptor represents the main leptin binding activity in human blood. Biochem Biophys Res Commun 283: 982–988PubMedGoogle Scholar
  106. Lau DC, Shillabeer G, Wong KL, Tough SC, Russell JC (1990) Influence of paracrine factors on preadipocyte replication and differentiation. Int J Obes 14Suppl 3: 193–201PubMedGoogle Scholar
  107. Licinio J, Mantzoros C, Negrao AB et al. (1997) Human leptin levels are pulsatile and inversely related to pituitary-adrenal function. Nat Med 3: 575–579PubMedGoogle Scholar
  108. Lillioja S, Mott DM, Howard BV et al. (1988) Impaired glucose tolerance as a disorder of insulin action. Longitudinal and cross-sectional studies in Pima Indians. N Engl J Med 318: 1217–1225PubMedGoogle Scholar
  109. Loffreda S, Yang SQ, Lin HZ et al. (1998) Leptin regulates proinflammatory immune responses. FASEB J 12: 57–65PubMedGoogle Scholar
  110. Maeda N, Shimomura I, Kishida K et al. (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8: 731–737PubMedGoogle Scholar
  111. Maffeis C, Schutz Y (2004) Regulation des Energiestoffwechsels. In: Wabitsch M, Hebebrand J, Kiess W, Zwiauer K (Hrsg) Adipositas bei Kindern und Jugendlichen. Springer, Berlin Heidelberg New York, S 133–141Google Scholar
  112. Marin P, Oden B, Bjorntorp P (1995) Assimilation and mobilization of triglycerides in subcutaneous abdominal and femoral adipose tissue in vivo in men: effects of androgens. J Clin Endocrinol Metab 80: 239–243PubMedGoogle Scholar
  113. Matsuzawa Y, Funahashi T, Kihara S, Shimomura I (2004) Adiponectin and metabolic syndrome. Arterioscler Thromb Vasc Biol 24: 29–33PubMedGoogle Scholar
  114. Miles PD, Romeo OM, Higo K, Cohen A, Rafaat K, Olefsky JM (1997) TNF-alpha-induced insulin resistance in vivo and its prevention by troglitazone. Diabetes 46: 1678–1683PubMedGoogle Scholar
  115. Minn AH, Patterson NB, Pack S et al. (2003) Resistin is expressed in pancreatic islets. Biochem Biophys Res Commun 310: 641–645PubMedGoogle Scholar
  116. Minokoshi Y, Alquier T, Furukawa N et al. (2004) AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature 428:569–574PubMedGoogle Scholar
  117. Mohamed-Ali V, Pinkney JH, Coppack SW (1998) Adipose tissue as an endocrine and paracrine organ. Int J Obes 22: 1145–1158Google Scholar
  118. Montague CT, Farooqi IS, Whitehead JP et al. (1997) Congenital leptin deficiency is associated with severe early-onset obesity in humans. Nature 387: 903–908PubMedGoogle Scholar
  119. Morishima A, Grumbach MM, Simpson ER, Fisher C, Qin K (1995) Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab 80: 3689–3698PubMedGoogle Scholar
  120. Muller G, Ertl J, Gerl M, Preibisch G (1997) Leptin impairs metabolic actions of insulin in isolated rat adipocytes. J Biol Chem 272: 10585–10593PubMedGoogle Scholar
  121. Murray I, Havel PJ, Sniderman AD, Cianflone K (2000) Reduced body weight, adipose tissue, and leptin levels despite increased energy intake in female mice lacking acylation-stimulating protein. Endocrinology 141: 1041–1049PubMedGoogle Scholar
  122. Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH (1999) The disease burden associated with overweight and obesity. JAMA 282: 1523–1529PubMedGoogle Scholar
  123. Nakano Y, Tobe T, Choi-Miura NH, Mazda T, Tomita M (1996) Isolation and characterization of GBP28, a novel gelatin-binding protein purified from human plasma. J Biochem (Tokyo) 120: 803–812PubMedGoogle Scholar
  124. Neel JV (1999) The „thrifty genotype“ in 1998. Nutr Rev 57:S2–S9PubMedGoogle Scholar
  125. Nougues J, Reyne Y, Barenton B, Chery T, Garandel V, Soriano J (1993) Differentiation of adipocyte precursors in a serum-free medium is influenced by glucocorticoids and endogenously produced insulin-like growth factor-I. Int J Obes Relat Metab Disord 17: 159–167PubMedGoogle Scholar
  126. Oral EA, Simha V, Ruiz E et al. (2002) Leptin-replacement therapy for lipodystrophy. N Engl J Med 346: 570–578PubMedGoogle Scholar
  127. Patel L, Buckels AC, Kinghorn IJ et al. (2003) Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun 300: 472–476PubMedGoogle Scholar
  128. Pedersen SB, Fuglsig S, Sjogren P, Richelsen B (1996) Identification of steroid receptors in human adipose tissue. Eur J Clin Invest 26: 1051–1056PubMedGoogle Scholar
  129. Pelleymounter MA, Cullen MJ, Baker MB, Hecht R, Winters D, Boone T, Collins F (1995) Effects of the obese gene product on body weight regulation in ob/ob mice. Science 269: 540–543PubMedGoogle Scholar
  130. Perez C, Fernandez-Galaz C, Fernandez-Agullo T, Arribas C, Andres A, Ros M, Carrascosa JM (2004) Leptin impairs insulin signaling in rat adipocytes. Diabetes 53: 347–353PubMedGoogle Scholar
  131. Perseghin G, Scifo P, De Cobelli F et al. (1999) Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: a 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents. Diabetes 48: 1600–1606PubMedGoogle Scholar
  132. Perusse L, Rice T, Province MA et al. (2000) Familial aggregation of amount and distribution of subcutaneous fat and their responses to exercise training in the HERI-TAGE family study. Obes Res 8: 140–150PubMedGoogle Scholar
  133. Pinto S, Roseberry AG, Liu H et al. (2004) Rapid rewiring of arcuate nucleus feeding circuits by leptin. Science 304:110–115PubMedGoogle Scholar
  134. Pralong FP und Gaillard RC (2001) Neuroendocrine effects of leptin. Pituitary 4: 25–32PubMedGoogle Scholar
  135. Prins JB, O’Rahilly S (1997) Regulation of adipose cell number in man. Clin Sci (Lond) 92: 3–11PubMedGoogle Scholar
  136. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92(6):829–839PubMedGoogle Scholar
  137. Reaven GM (1988) Banting lecture 1988. Role of insulin resistance in human disease. Diabetes 37: 1595–1607PubMedGoogle Scholar
  138. Rechler MM (1997) Growth inhibition by insulin-like growth factor (IGF) binding protein-3-what’s IGF got to do with it? Endocrinology 138: 2645–2647PubMedGoogle Scholar
  139. Richardson RL, Wright JT, Kim JW, Hausman GJ (1992) Expression of transforming growth factor-beta (TGF-beta 1) and insulin-like growth factor II (IGF-II) messenger RNA in the developing subcutaneous tissue (SQ) of the fetal pig. Growth Dev Aging 56: 149–157PubMedGoogle Scholar
  140. Ristow M, Tschöp MH (2004) Obesity research and the physiology of energy homeostasis. In: Kiess W, Marcus C, Wabitsch M (eds) Obesity in childhood and adolescence. Karger, Basel, pp 63–79Google Scholar
  141. Ristow M, Muller-Wieland D, Pfeiffer A, Krone W, Kahn CR (1998) Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med 339:953–959PubMedGoogle Scholar
  142. Rohner-Jeanrenaud F (1999) Neuroendocrine regulation of nutrient partitioning. Ann NY Acad Sci 892: 261–271PubMedGoogle Scholar
  143. Rosen ED, Walkey CJ, Puigserver P, Spiegelman BM (2000) Transcriptional regulation of adipogenesis. Genes Dev 14:1293–1307PubMedGoogle Scholar
  144. Rosenbaum M, Leibel RL, Hirsch J (1997) Obesity. N Engl J Med 337: 396–407PubMedGoogle Scholar
  145. Ruan H, Hacohen N, Golub TR, Van Parijs L, Lodish HF (2002) Tumor necrosis factor-alpha suppresses adipocyte-specific genes and activates expression of preadipocyte genes in 3T3-L1 adipocytes: nuclear factor-kappaB activation by TNF-alpha is obligatory. Diabetes 51: 1319–1336PubMedGoogle Scholar
  146. Ruderman NB, Saha AK, Kraegen EW (2003) Minireview: malonyl CoA, AMP-activated protein kinase, and adiposity. Endocrinology 144: 5166–5171PubMedGoogle Scholar
  147. Rutter GA, Da S, X, Leclerc I (2003) Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis. Biochem J 375: 1–16PubMedGoogle Scholar
  148. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF (1995) A novel serum protein similar to Clq, produced exclusively in adipocytes. J Biol Chem 270: 26746–26749PubMedGoogle Scholar
  149. Schling P, Mallow H, Trindl A, Loffler G (1999) Evidence for a local renin angiotensin system in primary cultured human preadipocytes. Int J Obes Relat Metab Disord 23:336–341PubMedGoogle Scholar
  150. Sethi JK, Hotamisligil GS (1999) The role of TNF alpha in adipocyte metabolism. Semin Cell Dev Biol 10: 19–29PubMedGoogle Scholar
  151. Silva JE (1995) Thyroid hormone control of thermogenesis and energy balance. Thyroid 5: 481–492PubMedGoogle Scholar
  152. Simpson ER (2000) Role of aromatase in sex steroid action. J Mol Endocrinol 25: 149–156PubMedGoogle Scholar
  153. Sinha MK, Opentanova I, Ohannesian JP et al. (1996) Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting. J Clin Invest 98: 1277–1282PubMedGoogle Scholar
  154. Smith SJ, Cases S, Jensen DR et al. (2000) Obesity resistance and multiple mechanisms of triglyceride synthesis in mice lacking Dgat. Nat Genet 25: 87–90PubMedGoogle Scholar
  155. Song XM, Fiedler M, Galuska D et al. (2002) 5-Aminoimida-zole-4-carboxamide ribonucleoside treatment improves glucose homeostasis in insulin-resistant diabetic (ob/ob) mice. Diabetologia 45: 56–65PubMedGoogle Scholar
  156. Sopasakis VR, Sandqvist M, Gustafson B et al. (2004) High local concentrations and effects on differentiation implicate interleukin-6 as a paracrine regulator. Obes Res 12:454–460PubMedGoogle Scholar
  157. Spranger J, Kroke A, Mohlig M, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF (2003) Adiponectin and protection against type 2 diabetes mellitus. Lancet 361: 226–228PubMedGoogle Scholar
  158. Steppan CM, Lazar MA (2004) The current biology of resistin. J Intern Med 255: 439–447PubMedGoogle Scholar
  159. Steppan CM, Bailey ST, Bhat S et al. (2001) The hormone resistin links obesity to diabetes. Nature 409: 307–312PubMedGoogle Scholar
  160. Strobel A, Issad T, Camoin L, Ozata M, Strosberg AD (1998) A leptin missense mutation associated with hypogonadism and morbid obesity. Nat Genet 18: 213–215PubMedGoogle Scholar
  161. Stumvoll M, Haring H (2002a) Resistin and adiponectin — of mice and men. Obes Res 10: 1197–1199PubMedGoogle Scholar
  162. Stumvoll M, Haring H (2002b) The peroxisome proliferator-activated receptor-gamma2 Prol2Ala polymorphism. Diabetes 51: 2341–2347PubMedGoogle Scholar
  163. Stumvoll M, Tschritter O, Fritsche A et al. (2002) Association of the TG polymorphism in adiponectin (exon 2) with obesity and insulin sensitivity: interaction with family history of type 2 diabetes. Diabetes 51: 37–41PubMedGoogle Scholar
  164. Stumvoll M, Goldstein BJ, van Haeften TW (2005) Type 2 diabetes: principles of pathogenesis and therapy. Lancet 365(9467): 1333–1346PubMedGoogle Scholar
  165. Stunkard AJ, Harris JR, Pedersen NL, McClearn GE (1990) The body-mass index of twins who have been reared apart. N Engl J Med 322: 1483–1487PubMedGoogle Scholar
  166. Su EJ, Lombardi DM, Siegal J, Schwartz SM (1998) Angiotensin II induces vascular smooth muscle cell replication independent of blood pressure. Hypertension 31: 1331–1337PubMedGoogle Scholar
  167. Tan MS, Chang SY, Chang DM, Tsai JC, Lee YJ (2003) Association of resistin gene 3′-untranslated region +62G->A polymorphism with type 2 diabetes and hypertension in a Chinese population. J Clin Endocrinol Metab 88: 1258–1263PubMedGoogle Scholar
  168. Tartaglia LA (1997) The leptin receptor. J Biol Chem272:6093–6096PubMedGoogle Scholar
  169. The Lancet (2004) The catastrophic failures of public health. Lancet 363: 745Google Scholar
  170. Tomas E, Tsao TS, Saha AK et al. (2002) Enhanced muscle fat oxidation and glucose transport by ACRP30 globular domain: acetyl-CoA carboxylase inhibition and AMP-activated protein kinase activation. Proc Natl Acad Sci USA 99: 16309–16313PubMedGoogle Scholar
  171. Tomlinson JW, Moore J, Cooper MS et al. (2001) Regulation of expression of 11beta-hydroxysteroid dehydrogenase type 1 in adipose tissue: tissue-specific induction by cytokines. Endocrinology 142: 1982–1989PubMedGoogle Scholar
  172. Unger RH, Orci L (2000) Lipotoxic diseases of nonadipose tissues in obesity. Int J Obes Relat Metab Disord 24Suppl 4: S28–S32PubMedGoogle Scholar
  173. Vaisse C, Halaas JL, Horvath CM, Darnell JE Jr, Stoffel M, Friedman JM (1996) Leptin activation of Stat3 in the hypothalamus of wild-type and ob/ob mice but not db/db mice. Nat Genet 14: 95–97PubMedGoogle Scholar
  174. Vasseur F, Lepretre F, Lacquemant C, Froguel P (2003) The genetics of adiponectin. Curr Diab Rep 3: 151–158PubMedGoogle Scholar
  175. Verma S, Li SH, Wang CH, Fedak PW, Li RK, Weisel RD, Mickle DA (2003) Resistin promotes endothelial cell activation: further evidence of adipokine-endothelial interaction. Circulation 108: 736–740PubMedGoogle Scholar
  176. Wabitsch M, Fischer-Posovszky P (2004) Entwicklung und Regulation des Fettgewebes. In: Wabitsch M, Hebebrand J, Kiess W, Zwiauer K (Hrsg) Adipositas bei Kindern und Jugendlichen. Springer, Berlin Heidelberg New York, S 73–80Google Scholar
  177. Wanders RJA (2003) Genetic disorders of mitchondrial and peroxisomal fatty acid oxidation and peroxisome proliferator-activated receptors. In: Bachmann C, Koletzko B (eds) Genetic expression and nutrition, Vevey/Lippincott Williams & Wilkins, Philadelphia, pp 85–105Google Scholar
  178. Wang MY, Lee Y, Unger RH (1999) Novel form of lipolysis induced by leptin. J Biol Chem 274: 17541–17544PubMedGoogle Scholar
  179. Wang YX, Lee CH, Tiep S, Yu RT, Ham J, Kang H, Evans RM (2003) Peroxisome-proliferator-activated receptor delta activates fat metabolism to prevent obesity. Cell 113: 159–170PubMedGoogle Scholar
  180. Warne JP (2003) Tumour necrosis factor alpha: a key regulator of adipose tissue mass. J Endocrinol 177: 351–355PubMedGoogle Scholar
  181. Wauters M, Considine RV, Van Gaal LF (2000) Human leptin: from an adipocyte hormone to an endocrine mediator. Eur J Endocrinol 143: 293–311PubMedGoogle Scholar
  182. Welt CK, Chan JL, Bullen J et al. (2004) Recombinant human leptin in women with hypothalamic amenorrhea. N Engl J Med 351: 987–997PubMedGoogle Scholar
  183. Weyer C, Pratley RE, Salbe AD, Bogardus C, Ravussin E, Tataranni PA (2000) Energy expenditure, fat oxidation, and body weight regulation: a study of metabolic adaptation to long-term weight change. J Clin Endocrinol Metab 85:1087–1094PubMedGoogle Scholar
  184. Wilson MD, Blake WL, Salati LM, Clarke SD (1990) Potency of polyunsaturated and saturated fats as short-term inhibitors of hepatic lipogenesis in rats. J Nutr 120: 544–552PubMedGoogle Scholar
  185. Wu X, Motoshima H, Mahadev K, Stalker TJ, Scalia R, Goldstein BJ (2003) Involvement of AMP-activated protein kinase in glucose uptake stimulated by the globular domain of adiponectin in primary rat adipocytes. Diabetes 52: 1355–1363PubMedGoogle Scholar
  186. Xu XF, De Pergola G, Bjorntorp P (1991) Testosterone increases lipolysis and the number of beta-adrenoceptors in male rat adipocytes. Endocrinology 128: 379–382PubMedGoogle Scholar
  187. Yamamoto Y, Hirose H, Saito I, Nishikai K, Saruta T (2004) Adiponectin, an adipocyte-derived protein, predicts future insulin resistance: two-year follow-up study in Japanese population. J Clin Endocrinol Metab 89: 87–90PubMedGoogle Scholar
  188. Yamauchi T, Kamon J, Minokoshi Y et al. (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8:1288–1295PubMedGoogle Scholar
  189. Yamauchi T, Hara K, Kubota N et al. (2003 a) Dual roles of adiponectin/Acrp30 in vivo as an antidiabetic and antiatherogenic adipokine. Curr Drug Targets Immune Endocr Metabol Disord 3: 243–254PubMedGoogle Scholar
  190. Yamauchi T, Kamon J, Ito Y et al. (2003b) Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature 423: 762–769PubMedGoogle Scholar
  191. Yamauchi T, Kamon J, Waki H et al. (2003c) Globular adiponectin protected ob/ob mice from diabetes and ApoE-deficient mice from atherosclerosis. J Biol Chem 278: 2461–2468PubMedGoogle Scholar
  192. Yang G, Ge H, Boucher A, Yu X, Li C (2004) Modulation of direct leptin signaling by soluble leptin receptor. Mol Endocrinol 18: 1354–1362PubMedGoogle Scholar
  193. Yokota T, Meka CS, Medina KL et al. (2002) Paracrine regulation of fat cell formation in bone marrow cultures via adiponectin and prostaglandins. J Clin Invest 109: 1303–1310PubMedGoogle Scholar
  194. Yu YH, Zhu H (2003) Chronological changes in metabolism and functions of cultured adipocytes — A hypothesis for cell aging in mature adipocytes. Am J Physiol Endocrinol Metab 286: E402–410PubMedGoogle Scholar
  195. Zastrow O, Seidel B, Kiess W, Thiery J, Keller E, Böttner A, Kratzsch J (2003) The soluble leptin receptor is crucial for leptin action: evidence from clinical and experimental data. Int J Obes Relat Metab Disord 27: 1472–1478PubMedGoogle Scholar
  196. Zhang B, Berger J, Hu E, Szalkowski D, White-Carrington S, Spiegelman BM, Moller DE (1996) Negative regulation of peroxisome proliferator-activated receptor-gamma gene expression contributes to the antiadipogenic effects of tumor necrosis factor-alpha. Mol Endocrinol 10: 1457–1466PubMedGoogle Scholar
  197. Zhang JL, Qin YW, Zheng X, Qiu JL, Zou DJ (2003) Serum resistin level in essential hypertension patients with different glucose tolerance. Diabet Med 20: 828–831PubMedGoogle Scholar
  198. Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425–432PubMedGoogle Scholar
  199. Zhang Y, Olbort M, Schwarzer K et al. (1997) The leptin receptor mediates apparent autocrine regulation of leptin gene expression. Biochem Biophys Res Commun 240:492–495PubMedGoogle Scholar
  200. Zhou G, Myers R, Li Y et al. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest 108: 1167–1174PubMedGoogle Scholar
  201. Zong H, Ren JM, Young LH, Pypaert M, Mu J, Birnbaum MJ, Shulman GI (2002) AMP kinase is required for mitochondrial biogenesis in skeletal muscle in response to chronic energy deprivation. Proc Natl Acad Sci USA 99:15983–15987PubMedGoogle Scholar
  202. Zuk PA, Zhu M, Mizuno H et al. (2001) Multilineage cells from human adipose tissue: implications for cell-based therapies. Tissue Eng 7: 211–228PubMedGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2006

Authors and Affiliations

  • Antje Böttner
    • 1
  • Jürgen Kratzsch
    • 2
  • Annette G. Beck-Sickinger
    • 3
  • Michael Stumvoll
    • 4
  • Wieland Kiess
    • 1
  1. 1.Klinik und Poliklinik für Kinder und JugendlicheUniversitätsklinikum LeipzigLeipzig
  2. 2.Institut für Laboratoriumsmedizin Klinische Chemie und molekulare DiagnostikUniversität LeipzigLeipzig
  3. 3.Institut für BiochemieUniversität LeipzigLeipzig
  4. 4.Medizinische Klinik und Poliklinik IIIUniversität LeipzigLeipzig

Personalised recommendations