Expression levels of haem oxygenase-1 in the omental adipose tissue and peripheral blood mononuclear cells of women with polycystic ovary syndrome.

BACKGROUND Haem oxygenase (HO)-1, an enzyme that degrades haem, plays a key role in the regulation of the inflammatory response and insulin resistance. The aim of this study was to evaluate the role of HO-1 in the regulation of insulin resistance and glucose tolerance in women with polycystic ovary syndrome (PCOS). METHODS Omental adipose tissue and human peripheral blood mononuclear cells (PBMCs) from seven women with PCOS and five healthy controls, matched for BMI and age, were analysed using western blotting and the real-time PCR. RESULTS Women with PCOS were found to have significantly higher fasting and 2-h insulin levels, a significantly higher homeostasis model assessment insulin resistance index and a lower fasting glucose-to-insulin ratio (G(0)/I(0)) than the controls. The level of HO-1 protein in omental fat (P = 0.002), and the expression of HO-1 mRNA in omental fat and PBMCs from the women with PCOS were significantly lower (P = 0.002 and 0.05, respectively) than those of the controls. The expression of adiponectin mRNA in omental fat was also significantly lower (P = 0.02) in the women with PCOS than in the controls. However, there were no significant differences in the expression of tumour necrosis factor-α or interleukin-6 between the two groups. The level of HO-1 protein showed a significant positive correlation with the expression of HO-1 mRNA (r(2) = 0.786, P = 0.037) and adiponectin mRNA (r(2) = 0.7276, P <0.05). Serum insulin and glucose levels and BMI showed a significant negative correlation with the level of HO-1 (P< 0.05). CONCLUSIONS Our results suggest that the HO-1-adiponectin axis may be associated with the regulation of insulin resistance and glucose intolerance in women with PCOS.

[1]  K. Seow,et al.  Omental fat expression of adiponectin and adiponectin receptors in non-obese women with PCOS: a preliminary study. , 2009, Reproductive biomedicine online.

[2]  B. Ludvik,et al.  Diminished upregulation of visceral adipose heme oxygenase-1 correlates with waist-to-hip ratio and insulin resistance , 2009, International Journal of Obesity.

[3]  J. Ndisang,et al.  Upregulation of the heme oxygenase system ameliorates postprandial and fasting hyperglycemia in type 2 diabetes. , 2009, American journal of physiology. Endocrinology and metabolism.

[4]  V. Positano,et al.  Heme Oxygenase-1 Induction Remodels Adipose Tissue and Improves Insulin Sensitivity in Obesity-Induced Diabetic Rats , 2009, Hypertension.

[5]  W. Aronow,et al.  Treatment of Obese Diabetic Mice With a Heme Oxygenase Inducer Reduces Visceral and Subcutaneous Adiposity, Increases Adiponectin Levels, and Improves Insulin Sensitivity and Glucose Tolerance , 2008, Diabetes.

[6]  N. Abraham,et al.  Heme Oxygenase-Mediated Increases in Adiponectin Decrease Fat Content and Inflammatory Cytokines Tumor Necrosis Factor-α and Interleukin-6 in Zucker Rats and Reduce Adipogenesis in Human Mesenchymal Stem Cells , 2008, Journal of Pharmacology and Experimental Therapeutics.

[7]  N. Abraham,et al.  Pharmacological and Clinical Aspects of Heme Oxygenase , 2008, Pharmacological Reviews.

[8]  A. Dokras,et al.  Cardiovascular Disease Risk Factors in Polycystic Ovary Syndrome , 2008, Seminars in reproductive medicine.

[9]  E. V. van Beek,et al.  Young obese women with polycystic ovary syndrome have evidence of early coronary atherosclerosis. , 2007, The Journal of clinical endocrinology and metabolism.

[10]  D. Neglia,et al.  Beneficial effect of heme oxygenase-1 expression on myocardial ischemia-reperfusion involves an increase in adiponectin in mildly diabetic rats. , 2007, American journal of physiology. Heart and circulatory physiology.

[11]  F. Bach,et al.  Bilirubin and Biliverdin Treatment of Atherosclerotic Diseases , 2007, Cell cycle.

[12]  Gerald F Watts,et al.  Cardiovascular disease in the polycystic ovary syndrome: new insights and perspectives. , 2006, Atherosclerosis.

[13]  F. Orio,et al.  Endothelial dysfunction in PCOS: role of obesity and adipose hormones. , 2006, The American journal of medicine.

[14]  W. Durante,et al.  Metabolic syndrome increases endogenous carbon monoxide production to promote hypertension and endothelial dysfunction in obese Zucker rats. , 2006, American journal of physiology. Regulatory, integrative and comparative physiology.

[15]  K. Schousboe,et al.  Prevalence of endocrine diseases and abnormal glucose tolerance tests in 340 Caucasian premenopausal women with hirsutism as the referral diagnosis. , 2004, Fertility and sterility.

[16]  K. Sutton-Tyrrell,et al.  The relationship between C-reactive protein and carotid intima-media wall thickness in middle-aged women with polycystic ovary syndrome. , 2004, The Journal of clinical endocrinology and metabolism.

[17]  A. Pfeiffer,et al.  Adiponectin is independently associated with insulin sensitivity in women with polycystic ovary syndrome , 2004 .

[18]  D. Zander,et al.  Heme oxygenase-1 expression in human lungs with cystic fibrosis and cytoprotective effects against Pseudomonas aeruginosa in vitro. , 2004, American journal of respiratory and critical care medicine.

[19]  B. Kos-Kudła,et al.  Serum adiponectin in women with polycystic ovarian syndrome and its relation to clinical, metabolic and endocrine parameters , 2004, Journal of endocrinological investigation.

[20]  O. Zinder,et al.  Increased C-reactive protein levels in the polycystic ovary syndrome: a marker of cardiovascular disease. , 2004, The Journal of clinical endocrinology and metabolism.

[21]  F. Orio,et al.  Adiponectin levels in women with polycystic ovary syndrome. , 2003, The Journal of clinical endocrinology and metabolism.

[22]  G. Villuendas,et al.  Obesity, and not insulin resistance, is the major determinant of serum inflammatory cardiovascular risk markers in pre-menopausal women , 2003, Diabetologia.

[23]  V. Castracane,et al.  Polycystic ovarian syndrome and insulin resistance in white and Mexican American women: a comparison of two distinct populations. , 2002, American journal of obstetrics and gynecology.

[24]  H. Lodish,et al.  ACRP30, a new hormone controlling fat and glucose metabolism. , 2002, European journal of pharmacology.

[25]  J. Ingwall,et al.  Cardiac-Specific Expression of Heme Oxygenase-1 Protects Against Ischemia and Reperfusion Injury in Transgenic Mice , 2001, Circulation research.

[26]  E. Diamanti-Kandarakis,et al.  A survey of the polycystic ovary syndrome in the Greek island of Lesbos: hormonal and metabolic profile. , 1999, The Journal of clinical endocrinology and metabolism.

[27]  D. Langdon A Fasting Glucose to Insulin Ratio Is a Useful Measure of Insulin Sensitivity in Women with Polycystic Ovary Syndrome , 1999 .

[28]  Philipp E. Scherer,et al.  The crystal structure of a complement-1q family protein suggests an evolutionary link to tumor necrosis factor , 1998, Current Biology.

[29]  A. Dunaif,et al.  Insulin resistance and the polycystic ovary syndrome: mechanism and implications for pathogenesis. , 1997, Endocrine reviews.

[30]  R. Turner,et al.  Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man , 1985, Diabetologia.

[31]  Julia K Mader,et al.  Adipose tissue, inflammation and cardiovascular disease. , 2010, Revista da Associacao Medica Brasileira.

[32]  B. Fauser,et al.  Revised 2003 consensus on diagnostic criteria and long-term health risks related to polycystic ovary syndrome (PCOS). , 2004, Human reproduction.

[33]  K. Seow,et al.  Serum and adipocyte resistin in polycystic ovary syndrome with insulin resistance. , 2004, Human reproduction.

[34]  W. Dodson,et al.  Prevalence and predictors of risk for type 2 diabetes mellitus and impaired glucose tolerance in polycystic ovary syndrome: a prospective, controlled study in 254 affected women. , 1999, The Journal of clinical endocrinology and metabolism.