Insulin and Metformin Regulate Circulating and Adipose Tissue Chemerin

Abstract

OBJECTIVETo assess chemerin levels and regulation in sera and adipose tissue from women with polycystic ovary syndrome (PCOS) and matched control subjects.RESEARCH DESIGN AND METHODSReal-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.RESULTSSerum 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).CONCLUSIONSSerum and adipose tissue chemerin levels are increased in women with PCOS and are upregulated by insulin. Metformin treatment decreases serum chemerin in these women.

Differential Patterns of Serum Concentration and Adipose Tissue Expression of Chemerin in Obesity: Adipose Depot Specificity and Gender Dimorphism

“…Similar to previous reports, we found a positive, statistically significant correlation between circulating chemerin and BMI. In contrast to these same reports, we found no association between circulating chemerin and insulin resistance markers (Bozaoglu et al, 2007;Sell et al, 2010;Tan et al, 2009). The role of chemerin in insulin sensitivity/resistance is still a matter of controversy.…”

“…In the wild-type mice, chemerin and CMKLR1 were highly expressed in white adipose relative to brown adipose tissue; however, in the ob/ob mice, chemerin mRNA expression was upregulated in brown but not white fat and hence, chemerin levels became similar in the two types of adipose tissue. Chemerin mRNA levels in paired adipose tissue samples obtained from patients with polycystic ovarian syndrome (PCOS) were recently published (Tan et al, 2009). A significant increase in chemerin mRNA expression in subcutaneous and omental adipose tissue in PCOS compared to normal subjects was reported, although no fat-depot-specific differences in chemerin mRNA levels were detected in either group.…”

La chémérine

“…Ce syndrome comporte à la fois des troubles de la fertilité (hyperandrogénie, cycles irréguliers et ovaires micropolykystiques à l'échographie) et des troubles du métabolisme (obésité et insulinorésistance). Or, il est intéressant d'observer une augmentation significative des taux de chémérine dans le plasma et le tissu adipeux chez des patientes atteintes de SOPK [36,42]. La metformine [53], un agent antidiabétique, abolit cette augmentation plasmatique de la chémérine [36].…”

“…Or, il est intéressant d'observer une augmentation significative des taux de chémérine dans le plasma et le tissu adipeux chez des patientes atteintes de SOPK [36,42]. La metformine [53], un agent antidiabétique, abolit cette augmentation plasmatique de la chémérine [36]. Dans le modèle de rates stimulées par la 5 alpha-dihydrotestostérone, l'expression (ARNm et protéine) dans les ovaires de la chémérine et de son récepteur (CMKLR1) est plus élevée [43].…”

“…Chez la femme, les concentrations sériques de plusieurs adipocytokines, comme la leptine [46,47], la visfatine [46], la résistine [46,47], ainsi que celle du TNF- [47], sont plus élevées en fin de grossesse, alors que les taux d'adiponectine circulante [46,47] sont diminués. De la même manière, la concentration de chémérine augmente au cours de la grossesse chez la femme, contrairement à ce hyperinsulinémie prolongée provoque une augmentation de la concentration de chémérine chez des individus sains [36]. La chémérine pourrait donc être, non seulement un révélateur de l'inflammation, mais aussi un indicateur du métabolisme glucidique.…”