Insulin and metformin regulate circulating and adipose tissue chemerin.
OBJECTIVE
To assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects.


METHODS
Real-time RT-PCR and Western blotting were used to assess mRNA and protein expression of chemerin. Serum chemerin was measured by enzyme-linked immunosorbent assay. We investigated the in vivo effects of insulin on serum chemerin levels via a prolonged insulin-glucose infusion. Ex vivo effects of insulin, metformin, and steroid hormones on adipose tissue chemerin protein production and secretion into conditioned media were assessed by Western blotting and enzyme-linked immunosorbent assay, respectively.


RESULTS
Serum chemerin, subcutaneous, and omental adipose tissue chemerin were significantly higher in women with PCOS (n = 14; P < 0.05, P < 0.01). Hyperinsulinemic induction in human subjects significantly increased serum chemerin levels (n = 6; P < 0.05, P < 0.01). In adipose tissue explants, insulin significantly increased (n = 6; P < 0.05, P < 0.01) whereas metformin significantly decreased (n = 6; P < 0.05, P < 0.01) chemerin protein production and secretion into conditioned media, respectively. After 6 months of metformin treatment, there was a significant decrease in serum chemerin (n = 21; P < 0.01). Importantly, changes in homeostasis model assessment-insulin resistance were predictive of changes in serum chemerin (P = 0.046).


CONCLUSIONS
Serum and adipose tissue chemerin levels are increased in women with PCOS and are upregulated by insulin. Metformin treatment decreases serum chemerin in these women.
Tan
Bee K
BK
Endocrinology and Metabolism Group, Clinical Sciences Research Institute, Warwick Medical School, University of Warwick, Coventry, U.K.
Chen
Jing
J
Farhatullah
Syed
S
Adya
Raghu
R
Kaur
Jaspreet
J
Heutling
Dennis
D
Lewandowski
Krzysztof C
KC
O'Hare
J Paul
JP
Lehnert
Hendrik
H
Randeva
Harpal S
HS
D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000735:Androstenedione / Q000494:pharmacology; D019314:Dehydroepiandrosterone Sulfate / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D005947:Glucose / Q000008:administration & dosage; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000494:pharmacology; D007328:Insulin / Q000008:administration & dosage* / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D008687:Metformin / Q000008:administration & dosage* / Q000494:pharmacology; D009852:Omentum / Q000187:drug effects / Q000378:metabolism; D009924:Organ Culture Techniques; D011085:Polycystic Ovary Syndrome / Q000188:drug therapy* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D019707:Receptors, Chemokine / Q000097:blood* / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013739:Testosterone / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects; D055815:Young Adult
C102741:CMKLR1 protein, human; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D013739:Testosterone; D000735:Androstenedione; D004958:Estradiol; D019314:Dehydroepiandrosterone Sulfate; D008687:Metformin; D005947:Glucose