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.