Tan Bee K, Heutling Dennis, Chen Jing, Farhatullah S, Adya Raghu, Keay Stephen D, Kennedy C Richard, Lehnert Hendrik, Randeva Harpal S
Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK.
Diabetes. 2008 Jun;57(6):1501-7. doi: 10.2337/db08-0127. Epub 2008 Mar 28.
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.
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.
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).
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.
多囊卵巢综合征（PCOS）与胰岛素抵抗和肥胖相关。内脏脂肪组织衍生的丝氨酸蛋白酶抑制剂（vaspin）水平随高胰岛素血症和肥胖而升高。目前，尚无关于PCOS女性体内vaspin的相关数据。因此，我们评估了PCOS女性及匹配的对照受试者皮下和网膜脂肪组织中vaspin的mRNA和蛋白水平，包括循环vaspin水平。我们还研究了脂肪组织vaspin的体外调节以及二甲双胍治疗对PCOS受试者循环vaspin水平的影响。
采用实时逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法评估vaspin的mRNA和蛋白表达。通过酶联免疫吸附测定法对血清vaspin进行定量。体外分析葡萄糖、胰岛素、性腺和肾上腺类固醇对脂肪组织vaspin的影响。
PCOS女性网膜脂肪组织中循环vaspin水平（P < 0.05）、vaspin mRNA（P < 0.05）和蛋白水平（P < 0.05）显著更高。有趣的是，在网膜脂肪组织外植体中，葡萄糖显著增加了vaspin蛋白水平及其向条件培养基中的分泌（P < 0.001）。此外，二甲双胍治疗6个月后，PCOS女性血清vaspin水平显著降低（P < 0.001）。此外，多变量回归分析显示，二甲双胍治疗后，循环葡萄糖水平的变化可预测血清vaspin水平的变化（P = 0.014）。
我们首次报道超重PCOS女性血清和网膜脂肪组织中vaspin水平升高，且主要由葡萄糖对vaspin进行体外调节。更重要的是，二甲双胍治疗可降低血清vaspin水平，这是一项新发现。
