Low free plasma levels of retinol-binding protein 4 in insulin-resistant subjects with polycystic ovary syndrome

Abstract

It has been shown in animals and in humans that retinol-binding protein 4 (RBP4) production from adipose tissue leads to generalized insulin resistance (IR). A more sensitive marker of circulating RBP4 is free plasma RBP4 expressed by RBP4 to transthyretin (TTR) ratio, since in circulation RBP4 is bound to TTR. To investigate RBP4 levels in insulin-resistant women with polycystic ovary syndrome (PCOS) and to estimate free plasma RBP4 expressed by RBP4/TTR ratio. Thirty-five PCOS subjects were compared with 45 controls matched for age and body mass index (BMI). In each subject, fasting values of glucose, insulin, gonadotropins, estradiol, androgens, C-reactive protein (CRP), RBP4, and TTR were determined. PCOS subjects in comparison to controls were more insulin-resistant [homeostasis model assessment for IR (HOMA-IR): 2.6+/-0.3 vs 1.9+/-0.1, p=0.043], and presented lower RBP4 levels (28.3+/-1.1 vs 32.4+/-1.2 microg/ml, p=0.021) and RBP4/TTR ratio (0.26+/-0.01 vs 0.31+/-0.01, p=0.0014). When RBP4 and RBP4/TTR values where stratified according to BMI status (obese, overweight, and lean subjects), it was noticed that both RBP4 and RBP4/TTR values in lean PCOS were significantly lower than in controls (RBP4: 25.0+/-5.5 vs 34.1+/-9.0 microg/ml, p=0.0063, RBP4/TTR: 0.25+/-0.3 vs 0.35+/-0.1, p=0.016). No correlation was observed between RBP4 and RBP4/TTR with any hormonal or metabolic parameter including BMI. RBP4 and free plasma RBP4 expressed as RBP4/TTR ratio are statistically and significantly lower in insulin-resistant PCOS subjects in comparison to controls. Therefore, our findings do not confirm a link between IR, neither with RBP4 nor with free plasma RBP4 levels. The significance of these findings remains to be elucidated, since RBP4 might prove to have different actions, like other adipokines, from humans and rodents.