Metformin decreases the adipokine vaspin in overweight women with polycystic ovary syndrome concomitant with improvement in insulin sensitivity and a decrease in insulin resistance.
OBJECTIVE
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Tan
Bee K
BK
Endocrinology & Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, UK.
Heutling
Dennis
D
Chen
Jing
J
Farhatullah
S
S
Adya
Raghu
R
Keay
Stephen D
SD
Kennedy
C Richard
CR
Lehnert
Hendrik
H
Randeva
Harpal S
HS
D000273:Adipose Tissue / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000728:Androgens / Q000097:blood; D001706:Biopsy; D001786:Blood Glucose / Q000378:metabolism; D016207:Cytokines / Q000235:genetics; D004958:Estradiol / Q000097:blood; D005260:Female; D058851:GPI-Linked Proteins; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D037102:Lectins / Q000235:genetics; D008687:Metformin / Q000627:therapeutic use*; D009924:Organ Culture Techniques; D050177:Overweight / Q000097:blood* / Q000150:complications / Q000188:drug therapy; D018579:Patient Selection; D011085:Polycystic Ovary Syndrome / Q000097:blood* / Q000150:complications; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015843:Serpins / Q000097:blood* / Q000235:genetics
D000728:Androgens; D001786:Blood Glucose; D016207:Cytokines; D058851:GPI-Linked Proteins; D007004:Hypoglycemic Agents; C432397:ITLN1 protein, human; D007328:Insulin; D037102:Lectins; C507339:SERPINA12 protein, human; D015843:Serpins; D004958:Estradiol; D008687:Metformin