Metformin Decreases the Adipokine Vaspin in Overweight Women with the Polycystic Ovary Syndrome: Concomitant Improvement in Insulin Sensitivity and a Decrease in Insulin Resistance

Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Vaspin levels increase with hyperinsulinemia and obesity. Currently, no data exists on vaspin in PCOS women. Objectives: To assess mRNA and protein levels of vaspin from subcutaneous (sc) and omental (om) adipose tissue (AT) of PCOS women and matched controls, including circulating vaspin. Ex vivo regulation of AT vaspin and the effects of metformin treatment on circulating vaspin levels in PCOS subjects were also studied. Research Design and Methods: Real-time RT-PCR and western blotting were used to assess mRNA and protein expression of vaspin. Serum vaspin was quantified by ELISA. The effects of D-glucose, insulin, gonadal and adrenal steroids on AT vaspin were analysed ex vivo. Results: There were significantly higher levels of circulating vaspin (P < 0.05), vaspin mRNA (P < 0.05) and protein (P < 0.05) in om AT of PCOS women. Interestingly, in om AT explants, glucose significantly increased vaspin protein levels and secretion into conditioned media (P < 0.001). Also, after 6 months of metformin treatment, there was a significant decrease in serum vaspin levels in PCOS women (P < 0.001). Furthermore, multivariate regression analysis revealed that following metformin therapy, changes in circulating glucose levels was predictive of changes in serum vaspin levels (P = 0.014). Conclusions: We report for the first time elevated serum and om AT levels of vaspin in overweight PCOS women, and its ex vivo regulation mainly by glucose. More importantly, metformin treatment decreases serum vaspin levels, a novel observation. 3 olycystic ovary syndrome (PCOS) is the most commonly encountered endocrine disorder of women, affecting 5-10% of all women in the reproductive age (1). PCOS is characterised by menstrual dysfunction, hyperandrogenism and associated with insulin resistance (IR), pancreatic β-cell dysfunction, impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), dyslipidemia and visceral obesity (1, 2). Adipokines play an important role in the pathogenesis of insulin resistance, diabetes, and atherosclerosis (3). It is reported that accumulation of visceral adipose tissue poses a greater cardio-metabolic risk than subcutaneous adipose tissue (4, 5). Recently, a novel adipokine named 'vaspin' (visceral adipose tissue-derived serine protease inhibitor) was identified in obese, diabetic, Otsuka Long-Evans Tokushima (OLETF) rats. Vaspin levels peaked in visceral adipose tissue at 30 weeks, the age when insulin levels were maximal in these rats; however, vaspin levels decreased with worsening of diabetes at 50 weeks. Also, vaspin was found to significantly improve glucose …