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

¹ Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K
² 1st Medical Department, University of Lübeck Medical School, Lübeck, Germany

Corresponding author: Dr. Harpal S. Randeva, MBCHB, FRCP, MD, PhD, Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, U.K. E-mail: harpal.randeva{at}warwick.ac.uk

Abbreviations: AUC, area under the curve; DHEA-S, dehydroxyepiandrostenedione-sulfate; HOMA, homeostasis model assessment; HOMA-β, HOMA of β-cell function; HOMA-IR, HOMA of insulin resistance; OGTT, oral glucose tolerance test; PCOS, polycystic ovary syndrome; vaspin, visceral adipose tissue–derived serine protease inhibitor; WHR, waist-to-hip ratio

OBJECTIVE—Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Vaspin (visceral adipose tissue–derived serine protease inhibitor) levels increase with hyperinsulinemia and obesity. Currently, no data exists on vaspin in PCOS women. We therefore assessed mRNA and protein levels of vaspin, including circulating vaspin, from subcutaneous and omental adipose tissue of PCOS women and matched control subjects. Ex vivo regulation of adipose tissue 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 enzyme-linked immunosorbent assay. The effects of D-glucose, insulin, and gonadal and adrenal steroids on adipose tissue vaspin were analyzed 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 omental adipose tissue of PCOS women. Interestingly, in omental adipose tissue 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 were predictive of changes in serum vaspin levels (P = 0.014).

CONCLUSIONS—We report, for the first time, elevated serum and omental adipose tissue levels of vaspin in overweight PCOS women and ex vivo regulation of vaspin, predominantly by glucose. More importantly, metformin treatment decreases serum vaspin levels, a novel observation.

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