Raised Serum, Adipocyte, and Adipose Tissue Retinol-Binding Protein 4 in Overweight Women with Polycystic Ovary Syndrome: Effects of Gonadal and Adrenal Steroids

Tan, Bee K.; Chen, Jing; Lehnert, Hendrik; Kennedy, Richard H.; Randeva, Harpal S.

doi:10.1210/jc.2007-0091

Cited by 84 publications

(88 citation statements)

References 21 publications

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“…Although PCOS is an insulinresistant state, PCOS per se and insulin resistance do not seem to be related to high RBP4 levels. We did not demonstrate a correlation between serum RBP4 levels and markers of insulin resistance in overweight women with PCOS at baseline, confirming previous observational PCOS studies (7,15). Other than that of Graham et al (4), most studies in weight-matched diabetic and obese subjects have not demonstrated a relationship with RBP4 and insulin resistance (5,6,8,10).…”

Section: Correlations With Change In Rbp4supporting

confidence: 78%

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Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

et al. 2008

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OBJECTIVE -Polycystic ovary syndrome (PCOS) is an insulin-resistant state with insulin resistance being an established therapeutic target; however, measurement of insulin resistance remains challenging. We aimed to 1) determine serum retinol-binding protein 4 (RBP4) levels (purported to reflect insulin resistance) in women with PCOS and control subjects, 2) examine the relationship of RBP4 to conventional markers of insulin resistance, and 3) examine RBP4 changes with interventions modulating insulin resistance in overweight women with PCOS.RESEARCH DESIGN AND METHODS -At baseline, 38 overweight women (BMI Ͼ27 kg/m 2 ) with PCOS and 17 weight-matched control subjects were compared. Women with PCOS were then randomly assigned to 6 months of a higher-dose oral contraceptive pill (OCP) (35 g ethinyl estradiol/2 mg cyproterone acetate) or metformin (1 g b.i.d.). Outcome measures were insulin resistance (total insulin area under the curve) on an oral glucose tolerance test, RBP4, and metabolic/inflammatory markers.RESULTS -Overweight women with PCOS were more insulin resistant than control subjects, yet RBP4 levels were not different in women with PCOS versus those in control subjects (35.4 Ϯ 4.3 vs. 28.9 Ϯ 3.1 g/ml, P ϭ 0.36). RBP4 correlated with cholesterol and triglycerides but not with insulin resistance. Metformin improved insulin resistance by 35%, whereas the OCP worsened insulin resistance by 33%. However, RBP4 increased nonsignificantly in both groups (43.7 Ϯ 6.3 vs. 42.6 Ϯ 5.5 g/ml, P ϭ 0.92).CONCLUSIONS -Overweight women with PCOS were more insulin resistant than control subjects, but this finding was not reflected by RBP4 levels. RBP4 correlated with lipid levels but not with insulin resistance markers. RBP4 levels did not change when insulin resistance was reduced by metformin or increased by the OCP. These data suggest that RBP4 is not a useful marker of insulin resistance in PCOS but may reflect other metabolic features of this condition.

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Section: Correlations With Change In Rbp4supporting

confidence: 78%

“…In contrast, human data are equivocal, with high adipocyte and plasma RBP4 levels being reported inconsistently in insulin-resistant states, including obesity, IGT, type 2 diabetes, and PCOS (3)(4)(5)(6)(7)(8)(9). Relationships of RBP4 with features of the metabolic syndrome have also been inconsistently demonstrated (4,6,8).…”

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confidence: 99%

Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

et al. 2008

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“…RBP4 may not be a 'common denominator' of all forms of insulin resistance. RBP4 can be affected by alterations of sex hormones, as evidenced by the fact that 17β-oestradiol can increase RBP4 mRNA expression and RBP4 secretion from human adipose tissue and women with polycystic ovary syndrome have elevated adipose tissue and serum RBP4 levels [40]. Furthermore, progesterone in the presence of oestradiol decreases RBP4 content in the female reproductive tract [41].…”

Section: Discussionmentioning

confidence: 99%

Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes

et al. 2008

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Aims/hypothesis Pregnancy is characterised by temporarily increased insulin resistance. Gestational diabetes occurs when pancreatic beta cell function is unable to compensate for this insulin resistance. Retinol-binding protein 4 (RBP4) could be related to insulin resistance. We hypothesised that RBP4 is elevated in gestational diabetes. Methods Serum RBP4, transthyretin and retinol were crosssectionally measured in 42 women with gestational diabetes and 45 pregnant controls. Of these, 20 women with and 22 without gestational diabetes were included in an additional longitudinal study. RBP4 was determined by enzyme immunometric assay (EIA) and western blot. Results Women with gestational diabetes had lower RBP4 EIA and western blot levels than controls (median 6.8 [interquartile range, 3.9-14.3] vs 11.3 [7.8-19.9] μg/ml, p<0.001 and 25.1 [21.7-29.6] vs 26.6 [23.5-32.2] μg/ml, p=0.026). Transthyretin and the RBP4:transthyretin molar ratio were comparable between the groups. Serum retinol was lower (p<0.001) and the RBP4 Western blot level: retinol molar ratio was higher in women with gestational diabetes (p=0.044). RBP4 was not associated with the glucose or homeostasis model assessment of insulin resistance (HOMA-IR), but in gestational diabetes the RBP4:retinol molar ratio correlated with blood glucose and negatively with 2 h post-load insulin. The RBP4:transthyretin ratio correlated with HOMA-IR and fasting insulin in controls. In women with gestational diabetes RBP4 EIA and western blot levels increased after delivery. Retinol increased in both groups, while transthyretin and the RBP4:transthyretin ratio were not altered after parturition. Conclusions/interpretation RBP4 measured by two different techniques is not elevated, but the RBP4:retinol molar ratio is higher and correlates with fasting blood glucose in women with gestational diabetes. Thus, the RBP4:retinol ratio and the RBP4:transthyretin ratio are more informative than RBP4 levels alone when assessing insulin-glucose homeostasis during pregnancy.

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“…Conversely, Yildizhan et al (2011) reported significantly higher RBP4 and homeostatic model assessment (HOMA) index in obese PCOS women as compared with nonobese PCOS and control groups. Tan et al (2007) investigated the expression of RBP4 in SC and OM adipose tissue in overweight women with PCOS and weight-matched controls, and assessed the effects of sex steroids on RBP4 expression in SC and OM fat explants. RBP4 protein levels were significantly higher in PCOS SC and OM adipose tissue.…”

Section: Visfatinmentioning

confidence: 99%

Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

Spritzer¹,

Lecke²,

Satler³

et al. 2015

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Polycystic ovary syndrome (PCOS), a complex condition that affects women of reproductive age, is characterized by ovulatory dysfunction and androgen excess. Women with PCOS present higher prevalence of obesity, central adiposity, and dyslipidemia, and face increased risk of type 2 diabetes. PCOS is closely linked to functional derangements in adipose tissue. Adipocytes seem to be prone to hypertrophy when exposed to androgen excess, as experienced by women with PCOS, and both adipose tissue hypertrophy and hyperandrogenism are related to insulin resistance. Hypertrophic adipocytes are more susceptible to inflammation, apoptosis, fibrosis, and release of free fatty acids. Disturbed secretion of adipokines may also impact the pathophysiology of PCOS through their influence on metabolism and on sex steroid secretion. Chronic low-grade inflammation in PCOS is also related to hyperandrogenism and to the hypertrophy of adipocytes, causing compression phenomena in the stromal vessels, leading to adipose tissue hypoperfusion and altered secretion of cytokines. Lifestyle changes are the first-line intervention for reducing metabolic risks in PCOS and the addition of an insulin-sensitizing drug might be required. Nevertheless, there is not sufficient evidence in favor of any specific pharmacologic therapies to directly oppose inflammation. Further studies are warranted to identify an adipokine that could serve as an indirect marker of adipocyte production in PCOS, representing a reliable sign of metabolic alteration in this syndrome.

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Raised Serum, Adipocyte, and Adipose Tissue Retinol-Binding Protein 4 in Overweight Women with Polycystic Ovary Syndrome: Effects of Gonadal and Adrenal Steroids

Cited by 84 publications

References 21 publications

Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

Retinol-Binding Protein 4 and Insulin Resistance in Polycystic Ovary Syndrome

Serum concentrations of retinol-binding protein 4 in women with and without gestational diabetes

Adipose tissue dysfunction, adipokines, and low-grade chronic inflammation in polycystic ovary syndrome

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