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Journal of Endocrinological Investigation

, Volume 25, Issue 10, pp 855–861 | Cite as

Adipose tissue hormones

  • Micheie Guerre-Millo
Review Article

Abstract

It is now widely accepted that white adipose tissue (WAT) secretes a number of peptide hormones, including leptin, several cytokines, adipsin and acylation-stimulating protein (ASP), angiotensinogen, plasminogen activator inhibitor-1 (PAI-1), adiponectin, resistin etc., and also produces steroids hormones. This newly discovered secretory function has shifted our view of WAT, which is no longer considered only an energy storage tissue but a major endocrine organ, at the heart of a complex network influencing energy homeostasis, glucose and lipid metabolism, vascular homeostasis, immune response and even reproduction. Virtually all known adipose secreted proteins are dysregulated when the WAT mass is markedly altered, either increased in the obese state or decreased in lipoatrophy. This strongly implicates adiposesecreted products in the ethiopathology and/or complications of both obesity and cachexia. This review discusses the physiological relevance of adipose secretion by focusing on protein and steroid hormones. Regulation of WAT secretion by the major regulatory factors impinging on the adipocytes, i.e. insulin, glucocorticoids, catecholamines and thiazolidinediones (TZD) will be addressed. The rationale for therapeutic strategies aimed at compensating adverse effects resulting from overproduction or lack of a specific adipose secretory product will be discussed.

Key-words

Obesity adipose tissue hormones WAT 

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References

  1. 1.
    Rosen E.D., Spiegelman B.M. Ppargamma: a nuclear regulator of metabolism, differentiation, and cell growth. J. Biol. Chem. 2001, 276: 37731–37734.PubMedCrossRefGoogle Scholar
  2. 2.
    Mohamed-Ali V., Pinkney J.H., Coppack S.W. Adipose tissue as an endocrine and paracrine organ. Int. J. Obes. Relat. Metab. Disord. 1998, 22: 1145-1158.Google Scholar
  3. 3.
    Trayhurn P., Beattie J.H. Physiological role of adipose tissue: white adipose tissue as an endocrine and secretory organ. Proc. Nutr. Soc. 2001, 60: 329–339.PubMedCrossRefGoogle Scholar
  4. 4.
    Fruhbeck G., Gomez-Ambrosi J., Muruzabal F.J., Burrell M.A. The adipocyte: a model for integration of endocrine and metabolic signaling in energy metabolism regulation. Am. J. Physiol. Endocrinol. Metab. 2001, 280: E827–E847.PubMedGoogle Scholar
  5. 5.
    Björntörp P. Endocrine abnormalities of obesity. Metabolism 1995, 44: 21–23.PubMedCrossRefGoogle Scholar
  6. 6.
    Masuzaki H., Paterson J., Shinyama H. et al. A transgenic model of visceral obesity and the metabolic syndrome. Science 2001, 294: 2166–2170.PubMedCrossRefGoogle Scholar
  7. 7.
    Cassis L.A., Saye J., Peach M.J. Location and regulation of rat angiotensinogen messenger RNA. Hypertension 1988, 11: 591–596.PubMedCrossRefGoogle Scholar
  8. 8.
    Frederich R.C.J., Kahn B.B., Peach M.J., Flier J.S. Tissuespecific nutritional regulation of angiotensinogen in adipose tissue. Hypertension 1992, 19: 339–344.PubMedCrossRefGoogle Scholar
  9. 9.
    Massiera F., Bloch-Faure M., Ceiler D. et al. Adipose angiotensinogen is involved in adipose tissue growth and blood pressure regulation. FASEB J. 2001, 15: 2727–2729.PubMedGoogle Scholar
  10. 10.
    Eriksson P., Reynisdottir S., Lonnqvist F., Stemme V., Hamsten A., Arner P. Adipose tissue secretion of plasminogen activator inhibitor-1 in non-obese and obese individuals. Diabetologia 1998, 41: 65–71.PubMedCrossRefGoogle Scholar
  11. 11.
    Samad F., Uysal K.T., Wiesbrock S.M., Pandey M., Hotamisligil G.S., Loskutoff D.J. Tumor necrosis factor-a is a key component in the obesity-linked elevation of plasminogen activator inhibitor 1. Proc. Natl. Acad. Sci. USA 1999, 96: 6902–6907.PubMedCentralPubMedCrossRefGoogle Scholar
  12. 12.
    Alessi M.C., Bastelica D., Morange P. et al. Plasminogen activator inhibitor 1, transforming growth factor-beta1, and BMI are closely associated in human adipose tissue during morbid obesity. Diabetes 2000, 49: 1374–1380.PubMedCrossRefGoogle Scholar
  13. 13.
    Kersten S., Mandard S., Tan N.S. et al. Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J. Biol. Chem. 2000, 275: 28488–28493.PubMedCrossRefGoogle Scholar
  14. 14.
    Yoon J.C., Chickering T.W., Rosen E.D. et al. Peroxisome proliferator-activated receptor gamma target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol. Cell Biol. 2000, 20 (14): 5343–5349.PubMedCentralPubMedCrossRefGoogle Scholar
  15. 15.
    Cook K.S., Min H.Y., Johnson D. et al. Adipsin: a circulating serine protease homolog secreted by adipose tissue and sciatic nerve. Science 1987, 237: 402–405.PubMedCrossRefGoogle Scholar
  16. 16.
    Coppack S.W. Pro-inflammatory cytokines and adipose tissue. Proc. Nutr. Soc. 2001, 60: 349–356.PubMedCrossRefGoogle Scholar
  17. 17.
    Murray I., Sniderman A.D., Havel P.J., Cianflone K. Acylation stimulating protein (ASP) deficiency alters postprandial and adipose tissue metabolism in male mice. J. Biol. Chem. 1999, 274: 36219–36225.PubMedCrossRefGoogle Scholar
  18. 18.
    Saleh J., Blevins J.E., Havel P.J., Barrett J.A., Gietzen D. W., Cianflone K. Acylation stimulating protein (ASP) acute effects on postprandial lipemia and food intake in rodents. Int. J. Obes. Relat. Metab. Disord. 2001, 25: 705–713.PubMedCrossRefGoogle Scholar
  19. 19.
    Hotamisligil G.S., Spiegelman B.M. Tumor necrosis factor alpha: a key component of the obesity-diabetes link. Diabetes 1994, 43: 1271–1278.PubMedCrossRefGoogle Scholar
  20. 20.
    Hotamisligil G.S., Shargill N.S., Spiegelman B.M. Adipose expression of tumor necrosis factor-alpha: direct role in obesity-linked insulin resistance. Science 1993, 259: 87–91.PubMedCrossRefGoogle Scholar
  21. 21.
    Uysal K.T., Wiesbrock S.M., Marino M.W., Hotamisligil G.S. Protection from obesity-induced insulin resistance in mice lacking TNF-alpha function. Nature 1997, 389: 610–614.PubMedCrossRefGoogle Scholar
  22. 22.
    Singh A.H., Liu S., Crombie D.L. et al. Differential effects of rexinoids and thiazolidinediones on metabolic gene expression in diabetic rodents. Mol. Pharmacol. 2001, 59: 765–773.Google Scholar
  23. 23.
    Kern P.A., Ranganathan S., Li C., 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.PubMedGoogle Scholar
  24. 24.
    Bastard J.P., Maachi M., Van Nhieu J.T. et al. Adipose tissue IL-6 content correlates with resistance to insulin activation of glucose uptake both in vivo and in vitro. J. Clin. Endocrinol. Metab. 2002, 87: 2084–2089.PubMedCrossRefGoogle Scholar
  25. 25.
    Wallenius V., Wallenius K., Ahren B. et al. Interleukin-6-deficient mice develop mature-onset obesity. Nat. Med. 2002, 8: 75–79.PubMedCrossRefGoogle Scholar
  26. 26.
    Wallenius K., Wallenius V., Sunter D., Dickson S.L., Jansson J.O. Intracerebroventricular interleukin-6 treatment decreases body fat in rats. Biochem. Biophys. Res. Commun. 2002, 293: 560–565.PubMedCrossRefGoogle Scholar
  27. 27.
    Campfield L.A., Smith F.J., Burn P. The OB protein (leptin) pathway—a link between adipose tissue mass and central neural networks. Horm. Metab. Res. 1996, 28: 619–632.PubMedCrossRefGoogle Scholar
  28. 28.
    Friedman J.M., Halaas J.L. Leptin and the regulation of body weight in mammals. Nature 1998, 395: 763–770.PubMedCrossRefGoogle Scholar
  29. 29.
    Ahima R.S., Flier J.S. Leptin. Annu. Rev. Physiol. 2000, 62: 413–437.PubMedCrossRefGoogle Scholar
  30. 30.
    Rayner D.V., Trayhurn P. Regulation of leptin production: sympathetic nervous system interactions. J. Mol. Med. 2001, 79: 8–20.PubMedCrossRefGoogle Scholar
  31. 31.
    Zhang Y., Proenca R., Maffei M., Barone M., Leopold L., Friedman J.M. Positional cloning of the mouse obese gene and its human homologue [published erratum appears in Nature 1995, 374 (6521): 479. Nature 1994, 372: 425–432.CrossRefGoogle Scholar
  32. 32.
    Tartaglia L.A., Dembski M., Weng X. et al. Identification and expression cloning of a leptin receptor, OB-R. Cell 1995, 83: 1263–1271.PubMedCrossRefGoogle Scholar
  33. 33.
    Farooqi I.S., Jebb S.A., Langmack G. et al. Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N. Engl. J. Med. 1999, 341: 879–884.PubMedCrossRefGoogle Scholar
  34. 34.
    Clement K., Vaisse C., Lahlou N. et al. A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. Nature 1998, 392: 398–401.PubMedCrossRefGoogle Scholar
  35. 35.
    Heymsfield S.B., Greenberg A.S., Fujioka K. et al. Recombinant leptin for weight loss in obese and lean adults: a randomized, controlled, dose-escalation trial. JAMA 1999, 282: 1568–1575.PubMedCrossRefGoogle Scholar
  36. 36.
    Ahima R.S., Prabakaran D., Mantzoros C. et al. Role of leptin in the neuroendocrine response to fasting. Nature 1996, 382: 250–252.PubMedCrossRefGoogle Scholar
  37. 37.
    Bluher M., Michael M.D., Peroni O.D. et al. Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev. Cell 2002, 3: 25–38.PubMedCrossRefGoogle Scholar
  38. 38.
    Trayhurn P., Hoggard N., Mercer J.G., Rayner D.V. Leptin: fundamental aspects. Int. J. Obes. Relat. Metab. Disord. 1999, 23 (1): 22–28.PubMedCrossRefGoogle Scholar
  39. 39.
    Mark A.L., Correia M.L., Rahmouni K., Haynes W.G. Selective leptin resistance: a new concept in leptin physiology with cardiovascular implications. J. Hypertens. 2002, 20: 1245–1250.PubMedCrossRefGoogle Scholar
  40. 40.
    Berg A.H., Combs T.P., Scherer P.E. ACRP30/adiponectin: an adipokine regulating glucose and lipid metabolism. Trends Endocrinol. Metab. 2002, 13: 84–89.PubMedCrossRefGoogle Scholar
  41. 41.
    Maeda N., Shimomura I., Kishida K. et al. Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat. Med. 2002, 8: 731–737.PubMedCrossRefGoogle Scholar
  42. 42.
    Matsuda M., Shimomura I., Sata M. et al. Role of adiponectin in preventing vascular stenosis. The missing link of adipovascular axis. J. Biol. Chem. 2002, 277: 37487–37491.PubMedCrossRefGoogle Scholar
  43. 43.
    Kubota N., Terauchi Y., Yamauchi T. et al. Disruption of adiponectin causes insulin resistance and neointimal formation. J. Biol. Chem. 2002, 277: 25863–25866.PubMedCrossRefGoogle Scholar
  44. 44.
    Ma K., Cabrero A., Saha P.K. et al. Increased beta -oxidation but no insulin resistance or glucose intolerance in mice lacking adiponectin. J. Biol. Chem. 2002, 277: 34658–34661.PubMedCrossRefGoogle Scholar
  45. 45.
    Yamauchi T., Kamon J., Waki H. et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat. Med. 2001, 7: 941–946.PubMedCrossRefGoogle Scholar
  46. 46.
    Steppan C.M., Bailey S.T., Bhat S. et al. The hormone resistin links obesity to diabetes. Nature 2001, 409: 307–312.PubMedCrossRefGoogle Scholar
  47. 47.
    Kim K.H., Lee K., Moon Y.S., Sul H.S. A cysteine-rich adipose tissue-specific secretory factor inhibits adipocyte differentiation. J. Biol. Chem. 2001, 276: 11252–11256.PubMedCrossRefGoogle Scholar
  48. 48.
    Steppan C.M., Lazar M.A. Resistin and obesity-associated insulin resistance. Trends Endocrinol. Metab. 2002, 13: 18–23.PubMedCrossRefGoogle Scholar
  49. 49.
    Way J.M., Gorgun C.Z., Tong Q. et al. Adipose tissue resistin expression is severely suppressed in obesity and stimulated by peroxisome proliferator-activated receptor? agonists. J. Biol. Chem. 2001, 276: 25651–25653.PubMedCrossRefGoogle Scholar
  50. 50.
    Le Lay S., Boucher J., Rey A. et al. Decreased resistin expression in mice with different sensitivities to a high-fat diet. Biochem. Biophys. Res. Commun. 2001, 289: 564–567.PubMedCrossRefGoogle Scholar
  51. 51.
    Savage D.B., Sewter C.P., Klenk E.S. et al. Resistin/Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptor-gamma action in humans. Diabetes 2001, 50: 2199–2202.PubMedCrossRefGoogle Scholar
  52. 52.
    Abel E.D., Peroni O., Kim J.K. et al. Adipose-selective targeting of the GLUT4 gene impairs insulin action in muscle and liver. Nature 2001, 409: 729–733.PubMedCrossRefGoogle Scholar

Copyright information

© Italian Society of Endocrinology (SIE) 2002

Authors and Affiliations

  1. 1.Centre de Recherche des CordeliersUniversité Pierre et Marie CurieParisFrance

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