Metformin treatment may increase omentin-1 levels in women with polycystic ovary syndrome.
OBJECTIVE
Polycystic ovary syndrome (PCOS) is associated with the metabolic syndrome. Decreased omentin-1 levels are associated with obesity and diabetes. To study the effects of metformin treatment on omentin-1 levels in PCOS subjects and effects of omentin-1 on in vitro migration and angiogenesis.


METHODS
Serum omentin-1 was measured by ELISA. Angiogenesis was assessed by studying capillary tube formation in human microvascular endothelial cells (HMEC-1) on growth factor reduced Matrigel. Endothelial cell migration assay was performed in a modified Boyden chamber. Nuclear factor-κB (NF-κB) was studied by stably transfecting HMEC-1 cells with a cis-reporter plasmid containing luciferase reporter gene linked to five repeats of NF-κB binding sites. Akt phosphorylation was assessed by Western blotting.


RESULTS
Serum omentin-1 was significantly lower in PCOS women (P < 0.05). After 6 months of metformin treatment, there was a significant increase in serum omentin-1 (P < 0.01). Importantly, changes in hs-CRP were significantly negatively correlated with changes in serum omentin-1 (P = 0.036). In vitro migration and angiogenesis were significantly increased in serum from PCOS women (P < 0.01) compared with matched control subjects; these effects were significantly attenuated by metformin treatment (P < 0.01) plausibly through the regulation of omentin-1 levels via NF-κB and Akt pathways. CRP and VEGF induced in vitro migration, and angiogenesis was significantly decreased by omentin-1.


CONCLUSIONS
Increases in omentin-1 levels may play a role but are not sufficient to explain the decreased inflammatory and angiogenic effects of sera from metformin-treated PCOS women.
Tan
Bee K
BK
Edocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK. b.k.tan.1@warwick.ac.uk
Adya
Raghu
R
Farhatullah
Syed
S
Chen
Jing
J
Lehnert
Hendrik
H
Randeva
Harpal S
HS
D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002196:Capillaries / Q000187:drug effects / Q000502:physiology; D002465:Cell Movement / Q000187:drug effects; D002784:Cholesterol / Q000097:blood; D016207:Cytokines / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D005260:Female; D058851:GPI-Linked Proteins / Q000097:blood / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D037102:Lectins / Q000097:blood / Q000187:drug effects / Q000378:metabolism*; D008687:Metformin / Q000627:therapeutic use*; D016328:NF-kappa B / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy / Q000378:metabolism*; D012016:Reference Values; D013739:Testosterone / Q000097:blood; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D016207:Cytokines; D058851:GPI-Linked Proteins; D007004:Hypoglycemic Agents; C432397:ITLN1 protein, human; D037102:Lectins; D016328:NF-kappa B; D014280:Triglycerides; D013739:Testosterone; D008687:Metformin; D002784:Cholesterol