title: 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.
abstract: 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.
  
  
  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.
authors.affiliation: MBCHB, FRCP, Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry CV4 7AL, UK.
authors.forename: Bee K
authors.initials: BK
authors.lastname: Tan
authors.forename: Raghu
authors.initials: R
authors.lastname: Adya
authors.forename: S
authors.initials: S
authors.lastname: Farhatullah
authors.forename: Kris C
authors.initials: KC
authors.lastname: Lewandowski
authors.forename: Paul
authors.initials: P
authors.lastname: O'Hare
authors.forename: Hendrik
authors.initials: H
authors.lastname: Lehnert
authors.forename: Harpal S
authors.initials: HS
authors.lastname: Randeva
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000032:analysis; D015992:Body Mass Index; D016207:Cytokines / Q000097:blood / Q000235:genetics*; D018076:DNA, Complementary / Q000235:genetics; D005260:Female; D058851:GPI-Linked Proteins; D005786:Gene Expression Regulation; D005947:Glucose / Q000502:physiology*; D006801:Humans; D007328:Insulin / Q000097:blood / Q000502:physiology*; D007333:Insulin Resistance / Q000235:genetics; D037102:Lectins / Q000097:blood / Q000235:genetics*; D008055:Lipids / Q000097:blood; D009765:Obesity / Q000235:genetics; D050177:Overweight / Q000235:genetics*; D018579:Patient Selection; D011085:Polycystic Ovary Syndrome / Q000097:blood / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics*; D012016:Reference Values; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D001786:Blood Glucose; D016207:Cytokines; D018076:DNA, Complementary; D058851:GPI-Linked Proteins; C432397:ITLN1 protein, human; D007328:Insulin; D037102:Lectins; D008055:Lipids; D012333:RNA, Messenger; D005947:Glucose