Tan Bee K, Adya Raghu, Farhatullah S, Lewandowski Kris C, O'Hare Paul, Lehnert Hendrik, Randeva Harpal S
MBCHB, FRCP, Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
Diabetes. 2008 Apr;57(4):801-8. doi: 10.2337/db07-0990. Epub 2008 Jan 3.
Polycystic ovary syndrome (PCOS) is associated with insulin resistance and obesity. Recent studies have shown that plasma omentin-1 levels decrease with obesity. Currently, no data exist on the relative expression and regulation of omentin-1 in adipose tissue of women with PCOS. The objective of this study was to assess mRNA and protein levels of omentin-1, including circulating omentin-1, in omental adipose tissue of women with PCOS and matched control subjects. Ex vivo and in vivo regulation of adipose tissue omentin-1 was also studied.
Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of omentin-1. Plasma omentin-1 was measured by enzyme-linked immunosorbent assay. The effects of d-glucose, insulin, and gonadal and adrenal steroids on adipose tissue omentin-1 were analyzed ex vivo. The in vivo effects of insulin (hyperinsulinemia) on omentin-1 levels were also assessed by a prolonged insulin-glucose infusion.
In addition to decreased plasma omentin-1 levels in women with PCOS (P < 0.05), compared with control subjects, there was significantly lower levels of omentin-1 mRNA (P < 0.01) and protein (P < 0.05) in omental adipose tissue of women with PCOS (P < 0.01). Furthermore, in omental adipose tissue explants, insulin and glucose significantly dose-dependently decreased omentin-1 mRNA expression, protein levels, and secretion into conditioned media (P < 0.05, P < 0.01). Also, hyperinsulinemic induction in healthy subjects significantly reduced plasma omentin-1 levels (P < 0.01).
Our novel findings reveal that omentin-1 is downregulated by insulin and glucose. These may, in part, explain the decreased omentin-1 levels observed in our overweight women with PCOS.
多囊卵巢综合征(PCOS)与胰岛素抵抗和肥胖相关。最近的研究表明,血浆网膜素-1水平随肥胖而降低。目前,关于PCOS女性脂肪组织中网膜素-1的相对表达和调节尚无数据。本研究的目的是评估PCOS女性和匹配的对照受试者网膜脂肪组织中网膜素-1的mRNA和蛋白质水平,包括循环中的网膜素-1。还研究了脂肪组织网膜素-1的体外和体内调节。
采用实时逆转录聚合酶链反应(RT-PCR)和蛋白质印迹法评估网膜素-1的mRNA和蛋白质表达。采用酶联免疫吸附测定法测定血浆网膜素-1。体外分析了d-葡萄糖、胰岛素、性腺和肾上腺类固醇对脂肪组织网膜素-1的影响。还通过延长胰岛素-葡萄糖输注评估了胰岛素(高胰岛素血症)对网膜素-1水平的体内影响。
与对照受试者相比,PCOS女性不仅血浆网膜素-1水平降低(P<0.05),而且PCOS女性网膜脂肪组织中网膜素-1的mRNA水平(P<0.01)和蛋白质水平(P<0.05)也显著降低(P<0.01)。此外,在网膜脂肪组织外植体中,胰岛素和葡萄糖显著剂量依赖性地降低网膜素-1的mRNA表达、蛋白质水平以及向条件培养基中的分泌(P<0.05,P<0.01)。同样,健康受试者的高胰岛素血症诱导显著降低了血浆网膜素-1水平(P<0.01)。
我们的新发现表明,网膜素-1受胰岛素和葡萄糖下调。这些可能部分解释了我们超重的PCOS女性中观察到的网膜素-1水平降低。