Adipose Tissue Dysfunction in Polycystic Ovary Syndrome

  • Jennifer Villa
  • Richard E. PratleyEmail author


Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder among premenopausal women. In addition to infertility, PCOS is associated with insulin resistance, features of the metabolic syndrome, and an increased risk for diabetes. Similar to individuals with metabolic syndrome, many women with PCOS manifest abdominal obesity, suggesting adipose tissue dysfunction. The adipose tissue of women with PCOS is characterized by hypertrophic adipocytes and impairments in lipolysis and insulin action. The expression and secretion of a wide variety of adipokines implicated in insulin resistance, including adiponectin and others, are also altered in PCOS. Collectively, the available data indicate that adipose tissue dysfunction plays a central role in the metabolic abnormalities observed in PCOS. Whether these abnormalities are primary or secondary to hyperandrogenism or other abnormalities in PCOS is not yet known.


Adipocyte Adipokine Insulin resistance Metabolic syndrome Androgen 



No potential conflicts of interest relevant to this article were reported.


Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. 1.
    • March WA, Moore VM, Willson KJ, Phillips DI, Norman RJ, Davies MJ: The prevalence of polycystic ovary syndrome in a community sample assessed under contrasting diagnostic criteria. Hum Reprod 2010, 25:544–551. This study compares the prevalence of PCOS using various diagnostic criteria and indicates that PCOS may be much more prevalent than commonly appreciated. PubMedCrossRefGoogle Scholar
  2. 2.
    The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and longterm health risks related to polycystic ovary syndrome (PCOS). Hum Reprod. 2004;19(1):41–7.CrossRefGoogle Scholar
  3. 3.
    Diamanti-Kandarakis E, Papavassiliou AG. Molecular mechanisms of insulin resistance in polycystic ovary syndrome. Trends Mol Med. 2006;12(7):324–32.PubMedCrossRefGoogle Scholar
  4. 4.
    Diamanti-Kandarakis E, Papavassiliou AG, Kandarakis SA, Chrousos GP. Pathophysiology and types of dyslipidemia in PCOS. Trends Endocrinol Metab. 2007;18(7):280–5.PubMedCrossRefGoogle Scholar
  5. 5.
    Escobar-Morreale HF, Luque-Ramírez M, González F. Circulating inflammatory markers in polycystic ovary syndrome: a systematic review and metaanalysis. Fertil Steril. 2011;95(3):1048–58.PubMedCrossRefGoogle Scholar
  6. 6.
    • Moran LJ, Misso ML, Wild RA, Norman RJ. Impaired glucose tolerance, type 2 diabetes and metabolic syndrome in polycystic ovary syndrome: a systematic review and meta-analysis. Hum Reprod Update. 2010, 16(4):347–63. This study highlights the markedly increased risk for diabetes among women with PCOS. PubMedCrossRefGoogle Scholar
  7. 7.
    Tomlinson J, Millward A, Stenhouse E, Pinkney J. Type 2 diabetes and cardiovascular disease in polycystic ovary syndrome: what are the risks and can they be reduced? Diabet Med. 2010;27(5):498–515.PubMedCrossRefGoogle Scholar
  8. 8.
    Alvarez-Blasco F, Botella-Carretero JI, San Millán JL, Escobar-Morreale HF. Prevalence and characteristics of the polycystic ovary syndrome in overweight and obese women. Arch Intern Med. 2006;166(19):2081–6.PubMedCrossRefGoogle Scholar
  9. 9.
    Azziz R, Woods KS, Reyna R, Key TJ, Knochenhauer ES, Yildiz BO. The prevalence and features of the polycystic ovary syndrome in an unselected population. J Clin Endocrinol Metab. 2004;89(6):2745–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Escobar-Morreale H, San Milla J, Abdominal adiposity and the polycystic ovary syndrome TRENDS in Endocrinology and Metabolism Vol.18 No.7Google Scholar
  11. 11.
    Albu JB, Kovera AJ, Frager DH, Johnson JA, Pi-Sunyer FX. Visceral fat and race-dependent health risks in obese non-diabetic premenopausal women. Diabetes. 1997;46:456–62.PubMedCrossRefGoogle Scholar
  12. 12.
    Marsden P, Murdoch A, Taylor R. Tissue insulin sensitivity and body weight in polycystic ovary syndrome. Clin Endocrinol. 2001;55:191–9.CrossRefGoogle Scholar
  13. 13.
    •• Mannerås-Holm L, Leonhardt H, Kullberg J, Jennische A, et al. Adipose Tissue Has Aberrant Morphology and Function in PCOS: Enlarged Adipocytes and Low Serum Adiponectin, But Not Circulating Sex Steroids, Are Strongly Associated with Insulin Resistance. J. Clin. Endocrinol. Metab. 2011, 96:E304-E311. This study comprehensively examines adipose tissue morphology and function in women with PCOS. PubMedCrossRefGoogle Scholar
  14. 14.
    Carmina E, Bucchieri S, Esposito A, Del Puente A, et al. Abdominal fat quantity and distribution in women with polycystic ovary syndrome and extent of its relation to insulin resistance. J Clin Endocrinol Metab. 2007;92:E2500–5.CrossRefGoogle Scholar
  15. 15.
    Lee YH, Pratley RE. The evolving role of inflammation in obesity and the metabolic syndrome. Curr Diab Rep. 2005;5(1):70–5.PubMedCrossRefGoogle Scholar
  16. 16.
    Hausman DB, DiGirolamo M, Bartness TJ, Hausman GJ, Martin RJ. The biology of white adipocyte proliferation. Obes Rev. 2001;2(4):239–54.PubMedCrossRefGoogle Scholar
  17. 17.
    Weisberg SP, McCann D, Desai M, et al. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest. 2003;112:1796–808.PubMedGoogle Scholar
  18. 18.
    Kershaw EE. Flier JS Adipose tissue as an endocrine organ. J Clin Endocrinol Metab. 2004;89:2548–56.PubMedCrossRefGoogle Scholar
  19. 19.
    Salans LB, Cushman SW, Weismann RE. Studies of human adipose tissue. Adipose cell size and number in nonobese and obese patients. J Clin Invest. 1973;52:929–41.PubMedCrossRefGoogle Scholar
  20. 20.
    Weyer C, Foley JE, Bogardus C, Tataranni PA, Pratley RE. Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts Type II diabetes independent of insulin resistance. Diabetologia. 2000;43:1498–506.PubMedCrossRefGoogle Scholar
  21. 21.
    Leonhardt W, Hanefeld M, Schneider H, Haller H. Human adipocyte volumes: maximum size, and correlation to weight index in maturity onset-diabetes. Diabetologia. 1972;8:287–91.PubMedCrossRefGoogle Scholar
  22. 22.
    Faulds G, Rydén M, Ek I, Wahrenberg H, Arner P. Mechanisms behind lipolytic catecholamine resistance of subcutaneous fat cells in the polycystic ovarian syndrome. J Clin Endocrinol Metab. 2003;88(5):2269–73.PubMedCrossRefGoogle Scholar
  23. 23.
    Ek I, Arner P, Bergqvist A, Carlstrom K, Wahrenberg H. Impaired adipocyte lipolysis in nonobese women with the polycystic ovary syndrome: a possible link to insulin resistance? J Clin Endocrinol Metab. 1997;82:1147–53.PubMedCrossRefGoogle Scholar
  24. 24.
    Ek I, Arner P, Ryde M, Holm C, Thorne A, Hoffstedt J, et al. A unique defect in the regulation of visceral fat cell lipolysis in the polycystic ovary syndrome as an early link to insulin resistance. Diabetes. 2002;51:484–92.PubMedCrossRefGoogle Scholar
  25. 25.
    Seow KM, Tsai YL, Hwang JL, Hsu WY, Ho LT, Juan CC. Omental adipose tissue overexpression of fatty acid transporter CD36 and decreased expression of hormone-sensitive lipase in insulin-resistant women with polycystic ovary syndrome. Hum Reprod. 2009;24(8):1982–8.PubMedCrossRefGoogle Scholar
  26. 26.
    Dicker A, Ryden M, Nashund E, Muehlen IE, Wiren M, Lafontan M, et al. Effect of testosterone on lipolysis in human pre-adipocytes from different fat depots. Diabetologia. 2004;47:420–8.PubMedCrossRefGoogle Scholar
  27. 27.
    Rosenbaum D, Haber RS, Dunaif A. Insulin resistance in polycystic ovary syndrome: decreased expression of GLUT-4 glucose transporters in adipocytes. Am J Physiol. 1993;264:E197–202.PubMedGoogle Scholar
  28. 28.
    Chang W, Goodarzi M, Williams H, Magoffin D, Pall M, Azziz R. Adipocytes from women with polycystic ovary syndrome demonstrate altered phosphorylation and activity of glycogen synthase kinase 3. Fertil Steril. 2008;90(6):2291–7.PubMedCrossRefGoogle Scholar
  29. 29.
    Corbould A, Dunaif A. The adipose cell lineage is not intrinsically insulin resistant in polycystic ovary syndrome. Metab Clin Exp. 2007;56:716–22.PubMedGoogle Scholar
  30. 30.
    Corbould A. Chronic testosterone treatment induces selective insulin resistance in subcutaneous adipocytes of women. J Endocrinol. 2007;192:585–94.PubMedCrossRefGoogle Scholar
  31. 31.
    Danforth Jr E. Failure of adipocyte differentiation causes type II diabetes mellitus? Nat Genet. 2000;26(1):13.PubMedCrossRefGoogle Scholar
  32. 32.
    Permana PA, Nair S, Lee YH, Luczy-Bachman G, Vozarova De Courten B, Tataranni PA. Subcutaneous abdominal preadipocyte differentiation in vitro inversely correlates with central obesity. Am J Physiol Endocrinol Metab. 2004;286(6):E958–62.PubMedCrossRefGoogle Scholar
  33. 33.
    Yang X, Jansson PA, Nagaev I, Jack MM, Carvalho E, Sunnerhagen KS, et al. Evidence of impaired adipogenesis in insulin resistance. Biochem Biophys Res Commun. 2004;317(4):1045–51.PubMedCrossRefGoogle Scholar
  34. 34.
    Corton M, Botella-Carretero J, Bengurıa A, Villuendas G, Zaballos A, et al. Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome. J Clin Endocrinol Metab. 2007;92:328–37.PubMedCrossRefGoogle Scholar
  35. 35.
    Gupta V, Bhasin S, Guo W, Singh R, Miki R, Chauhan P, et al. Effects of dihydrotestosterone on differentiation and proliferation of human mesenchymal stem cells and preadipocytes. Mol Cell Endocrinol. 2008;296(1–2):32–40.PubMedCrossRefGoogle Scholar
  36. 36.
    Roland AV, Nunemaker CS, Keller SR, Moenter SM. Prenatal androgen exposure programs metabolic dysfunction in female mice. J Endocrinol. 2010;207(2):213–23.PubMedCrossRefGoogle Scholar
  37. 37.
    Lee YH, Nair S, Rousseau E, Allison DB, Page GP, Tataranni PA, et al. Microarray profiling of isolated abdominal subcutaneous adipocytes from obese vs non-obese Pima Indians: increased expression of inflammation-related genes. Diabetologia. 2005;48(9):1776–83.PubMedCrossRefGoogle Scholar
  38. 38.
    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;372:425–32.PubMedCrossRefGoogle Scholar
  39. 39.
    Maffei M, Halaas J, Ravussin E, et al. Leptin levels in human and rodent: measurement of plasma leptin and obRNA in obese and weight-reduced subjects. Nat Med. 1995;1:1155–61.PubMedCrossRefGoogle Scholar
  40. 40.
    Mantzoros CS, Dunaif A, Flier JS. Leptin concentrations in the polycystic ovary syndrome. J Clin Endocrinol Metab. 1997;82(6):1687–91.PubMedCrossRefGoogle Scholar
  41. 41.
    • Carmina E, Bucchieri S, Mansueto P, Rini G, Ferin M, Lobo R. Circulating levels of adipose products and differences in fat distribution in the ovulatory and anovulatory phenotypes of polycystic ovary syndrome. Fertility and Sterility 2009, 91(4) supplement: 1332–1335. In this study, differences in several adipokines were demonstrated in ovulatory and anovulatory women with PCOS. PubMedCrossRefGoogle Scholar
  42. 42.
    Weyer C, Funahashi T, Tanaka S, Hotta K, Matsuzawa Y, Pratley RE, et al. Hypoadiponectinemia in obesity and type 2 diabetes: close association with insulin resistance and hyperinsulinemia. J Clin Endocrinol Metab. 2001;86:E1930–5.CrossRefGoogle Scholar
  43. 43.
    O’Connor A, Phelan N, Kyaw T, Boran G, Gibney J, Roche HM. High-molecular-weight adiponectin is selectively reduced in women with polycystic ovary syndrome independent of body mass index and severity of insulin resistance. J Clin Endocrinol Metab. 2010;95:1378–85.PubMedCrossRefGoogle Scholar
  44. 44.
    • Toulis KA, Goulis DG, Farmakiotis D, Georgopolous NA, Katsikis I, Tarlatzis BC, Papadimas I, Panidis D. Adiponectin levels in women with polycystic ovary syndrome: a systematic review and a meta-analysis. Human Reproduction Update 2009; 15 (3): 297–307. This systematic review documents the low levels of adiponectin observed in women with PCOS. PubMedCrossRefGoogle Scholar
  45. 45.
    Murat Y, Bukan N, Demirci H, Ozturk C, Kan E, Ayvaz G, et al. Serum resistin and adiponectin levels in women with polycystic ovary syndrome. Gynecol Endocrinol. 2009;25(4):246–52.CrossRefGoogle Scholar
  46. 46.
    Mlinar B, Pfeifer M, Vrtachnik-Bokal E, Jensterle M, Marc J. Decreased lipin 1β expression in visceral adipose tissue is associated with insulin resistance in polycystic ovary syndrome. Eur J Endocrinol. 2008;159:833–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Nishimura S, Manabe I, Nagasaki M, et al. CD8+ effector T cells contribute to macrophage recruitment and adipose tissue inflammation in obesity. Nat Med. 2009;15(8):914–20.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Diabetes and Metabolism Translational Medicine UnitUniversity of Vermont College of MedicineColchesterUSA

Personalised recommendations