Metabolic heterogeneity in polycystic ovary syndrome is determined by obesity: Plasma metabolomic approach using GC-MS

Clinical Chemistry

Volumn 58, Issue 6, 2012, Pages 999-1009

  Escobar Morreale, Héctor F ^a,b,c   Samino, Sara ^b,d   Insenser, María ^a,b,c   Vinaixa, María ^b,d   Luque Ramírez, Manuel ^a,b   Lasunción, Miguel A ^a,c,e   Correig, Xavier ^b,d  

^a HOSPITAL RAMÓN Y CAJAL   (Spain)

^b INSTITUTO DE SALUD CARLOS III   (Spain)

^c INSTITUTO RAMÓN Y CAJAL DE INVESTIGACIÓN SANITARIA IRYCIS   (Spain)

^d INSTITUT D INVESTIGACIÓ SANITÀRIA PERE VIRGILI IISPV   (Spain)

^e Instituto de Salud Carlos III   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

2 OXOISOCAPROIC ACID; ALANINE; ALPHA TOCOPHEROL; BRANCHED CHAIN AMINO ACID; CHOLESTEROL; GLYCEROL; LACTIC ACID; LINOLEIC ACID; LONG CHAIN FATTY ACID; OLEIC ACID;

ADULT; ARTICLE; CLINICAL ARTICLE; CONTROLLED STUDY; FEMALE; GAS CHROMATOGRAPHY; GLUCONEOGENESIS; GLUCOSE UTILIZATION; HUMAN; HYPERINSULINEMIA; INSULIN RESISTANCE; LIPOLYSIS; MASS SPECTROMETRY; METABOLIC DISORDER; METABOLISM; METABOLOMICS; OBESITY; OVARY POLYCYSTIC DISEASE; PHENOTYPE; PROTEIN SYNTHESIS;

ADULT; AMINO ACIDS, BRANCHED-CHAIN; CASE-CONTROL STUDIES; FEMALE; GAS CHROMATOGRAPHY-MASS SPECTROMETRY; GLUCOSE; HUMANS; HYPERINSULINISM; INSULIN RESISTANCE; LIPOLYSIS; METABOLOME; OBESITY; PLASMA; POLYCYSTIC OVARY SYNDROME; PREMENOPAUSE; YOUNG ADULT;

EID: 84861672693     PISSN: 00099147     EISSN: 15308561     Source Type: Journal    
DOI: 10.1373/clinchem.2011.176396     Document Type: Article

References (40)

1. Asuncion M, Calvo RM, San Millan JL, Sancho J, Avila S, Escobar-Morreale HF. A prospective study of the prevalence of the polycystic ovary syndrome in unselected Caucasian women from Spain. J Clin Endocrinol Metab 2000;85: 2434-8.
2. Escobar-Morreale HF, San Millan JL. Abdominal adiposity and the polycystic ovary syndrome. Trends Endocrinol Metab 2007;18:266 -72.
3. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. The Androgen Excess and PCOS Society criteria for the polycystic ovary syndrome: the complete task force report. Fertil Steril 2009;91: 456-88.
4. Ehrmann D, Barnes R, Rosenfield R, Cavaghan M, Imperial J. Prevalence of impaired glucose tolerance and diabetes in women with polycystic ovary syndrome. Diabetes Care 1999;22: 141-6. (Pubitemid 29028311)
5. Luque-Ramirez M, Alpanes M, Escobar-Morreale HF. The determinants of insulin sensitivity, beta-cell function, and glucose tolerance are different in patients with polycystic ovary syndrome than in women who do not have hyperandrogenism. Fertil Steril 2010;94:2214-21.
6. Salley KE, Wickham EP, Cheang KI, Essah PA, Karjane NW, Nestler JE. Glucose intolerance in polycystic ovary syndrome: a position statement of the Androgen Excess Society. J Clin Endocrinol Metab 2007;92:4546 -56.
7. Wild RA, Carmina E, Diamanti-Kandarakis E, Dokras A, Escobar-Morreale HF, Futterweit W, et al. Assessment of cardiovascular risk and prevention of cardiovascular disease in women with the polycystic ovary syndrome: a consensus statement by the Androgen Excess and Polycystic Ovary Syndrome (AE-PCOS) Society. J Clin Endocrinol Metab 2010;95:2038-49.
8. Escobar-Morreale HF, Insenser M, Corton M, San Millán JL, Peral B. Proteomics and genomics: a hypothesis-free approach to the study of the role of visceral adiposity in the pathogenesis of the polycystic ovary syndrome. Proteomics Clin Appl 2008;2:444 -56.
9. Corton M, Botella-Carretero JI, Benguria A, Villuendas G, Zaballos A, San Millan JL, et al. Differential gene expression profile in omental adipose tissue in women with polycystic ovary syndrome. J Clin Endocrinol Metab 2007;92:328-37. (Pubitemid 46075011)
10. Corton M, Botella-Carretero JI, Lopez JA, Camafeita E, San Millan JL, Escobar-Morreale HF, Peral B. Proteomic analysis of human omental adipose tissue in the polycystic ovary syndrome using two-dimensional difference gel electrophoresis and mass spectrometry. Hum Reprod 2008;23: 651-61. (Pubitemid 351651200)
11. Insenser M, Martinez-Garcia MA, Montes R, San-Millan JL, Escobar-Morreale HF. Proteomic analysis of plasma in the polycystic ovary syndrome identifies novel markers involved in iron metabolism, acute-phase response, and inflammation. J Clin Endocrinol Metab 2010;95:3863-70.
12. Dettmer K, Aronov PA, Hammock BD. Mass spectrometry-based metabolomics. Mass Spectrom Rev 2007;26:51-78. (Pubitemid 46051813)
13. Bain JR, Stevens RD, Wenner BR, Ilkayeva O, Muoio DM, Newgard CB. Metabolomics applied to diabetes research: moving from information to knowledge. Diabetes 2009;58:2429-43.
14. Escobar-Morreale HF, Sanchon R, San Millan JL. A prospective study of the prevalence of nonclassical congenital adrenal hyperplasia among women presenting with hyperandrogenic symptoms and signs. J Clin Endocrinol Metab 2008;93:527-33. (Pubitemid 351240826)
15. Zawadzki JK, Dunaif A. Diagnostic criteria for polycystic ovary syndrome: towards a rational approach. In: Dunaif A, Givens JR, Haseltine FP, Merriam GR, eds. Polycystic ovary syndrome, Vol. 4. Boston: Blackwell Scientific, 1992:377-84.
16. The Rotterdam ESHRE/ASRM-sponsored PCOS consensus workshop group. Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). Hum Reprod 2004;19:41-7.
17. Azziz R, Carmina E, Dewailly D, Diamanti-Kandarakis E, Escobar-Morreale HF, Futterweit W, et al. Position statement: criteria for defining polycystic ovary syndrome as a predominantly hyperandrogenic syndrome: an Androgen Excess Society guideline. J Clin Endocrinol Metab 2006; 91:4237- 45.
18. Martinez-Garcia MA, Luque-Ramirez M, San-Millan JL, Escobar-Morreale HF. Body iron stores and glucose intolerance in premenopausal women: role of hyperandrogenism, insulin resistance and genomic variants related to inflammation, oxidative stress and iron metabolism. Diabetes Care 2009;32:1525-30.
19. Matsuda M, DeFronzo RA. Insulin sensitivity indices obtained from oral glucose tolerance testing: comparison with the euglycemic insulin clamp. Diabetes Care 1999;22:1462-70. (Pubitemid 29418240)
20. Palazoglu M, Fiehn O. Metabolite identification in blood plasma using GC/MS and the Agilent Fiehn GC/MS metabolomics RTL library. Agilent Application Note 2009.
21. Dunn WB, Broadhurst D, Begley P, Zelena E, Francis-McIntyre S, Anderson N, et al. Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry. Nat Protoc 2011;6:1060-83.
22. Lin HM, Edmunds SI, Helsby NA, Ferguson LR, Rowan DD. Nontargeted urinary metabolite profiling of a mouse model of Crohn's disease. J Proteome Res 2009;8:2045-57.
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. (Pubitemid 27166656)
24. Mozaffarian D, Cao H, King IB, Lemaitre RN, Song X, Siscovick DS, Hotamisligil GS. Circulating palmitoleic acid and risk of metabolic abnormalities and new-onset diabetes. Am J Clin Nutr 2010;92:1350-8.
25. Dunaif A. Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. Endocr Rev 1997;18:774-800. (Pubitemid 28009567)
26. Setji TL, Holland ND, Sanders LL, Pereira KC, Diehl AM, Brown AJ. Nonalcoholic steatohepatitis and nonalcoholic fatty liver disease in young women with polycystic ovary syndrome. J Clin Endocrinol Metab 2006;91:1741-7.
27. Newgard CB, An J, Bain JR, Muehlbauer MJ, Stevens RD, Lien LF, et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab 2009;9: 311-26.
28. Suhre K, Meisinger C, Doring A, Altmaier E, Belcredi P, Gieger C, et al. Metabolic footprint of diabetes: a multiplatform metabolomics study in an epidemiological setting. PLoS ONE 2010;5: e13953.
29. Fernstrom JD. Branched-chain amino acids and brain function. J Nutr 2005;135:1539S-46S. (Pubitemid 40791667)
30. Ek I, Arner P, Ryden M, Holm C, Thorne A, Hoffstedt J, Wahrenberg H. 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. (Pubitemid 34764807)
31. Faulds G, Ryden 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; 88:2269-73. (Pubitemid 36549907)
32. Layman DK. The role of leucine in weight loss diets and glucose homeostasis. J Nutr 2003;133: 261S-7S.
33. Altmaier E, Ramsay SL, Graber A, Mewes HW, Weinberger KM, Suhre K. Bioinformatics analysis of targeted metabolomics: uncovering old and new tales of diabetic mice under medication. Endocrinology 2008;149:3478-89.
34. Biolo G, Declan Fleming RY, Wolfe RR. Physiologic hyperinsulinemia stimulates protein synthesis and enhances transport of selected amino acids in human skeletal muscle. J Clin Invest 1995;95:811-9.
35. Harris SE, Maruthini D, Tang T, Balen AH, Picton HM. Metabolism and karyotype analysis of oocytes from patients with polycystic ovary syndrome. Hum Reprod 2010;25:2305-15.
36. Notelovitz M. Androgen effects on bone and muscle. Fertil Steril 77 Suppl 4:S34-41, 2002. (Pubitemid 34465842)
37. Dunaif A, Segal KR, Shelley DR, Green G, Dobrjansky A, Licholai T. Evidence for distinctive and intrinsic defects in insulin action in polycystic ovary syndrome. Diabetes 1992;41: 1257-66.
38. Ciaraldi TP, Aroda V, Mudaliar S, Chang RJ, Henry RR. Polycystic ovary syndrome is associated with tissue-specific differences in insulin resistance. J Clin Endocrinol Metab 2009;94:157-63.
39. Ciampelli M, Fulghesu AM, Cucinelli F, Pavone V, Caruso A, Mancuso S, Lanzone A. Heterogeneity in beta cell activity, hepatic insulin clearance and peripheral insulin sensitivity in women with polycystic ovary syndrome. Hum Reprod 1997;12: 1897-901. (Pubitemid 27462465)
40. Fenkci V, Fenkci S, Yilmazer M, Serteser M. Decreased total antioxidant status and increased oxidative stress in women with polycystic ovary syndrome may contribute to the risk of cardiovascular disease. Fertil Steril 2003;80:123-7.