Omentin-1, a Novel Adipokine, Is Decreased in Overweight Insulin-Resistant Women With Polycystic Ovary Syndrome
Ex Vivo and In Vivo Regulation of Omentin-1 by Insulin and Glucose
- Bee K. Tan1,
- Raghu Adya1,
- S. Farhatullah1,
- Kris C. Lewandowski1,2,
- Paul O’Hare1,
- Hendrik Lehnert1,3 and
- Harpal S. Randeva1
- 1Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K
- 2Department of Endocrinology and Metabolic Diseases, the Medical University of Lodz and Polish Mother’s Memorial Research Institute, Lodz, Poland
- 31st Medical Department, University of Lübeck Medical School, Luebeck, Germany
- Address correspondence and reprint requests to Dr. Harpal S. Randeva, MBCHB, FRCP, MD, PhD, Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, U.K. E-mail:
OBJECTIVE—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.
RESEARCH DESIGN AND METHODS—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.
RESULTS—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).
CONCLUSIONS—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.
- DHEA-S, dehydroxyepiandrostenedione-sulfate
- ELISA, enzyme-linked immunosorbent assay
- HOMA, homeostasis model assessment
- PCOS, polycystic ovary syndrome
- WHR, waist-to-hip ratio
- Received July 17, 2007.
- Accepted December 23, 2007.