Elsevier

Clinica Chimica Acta

Volume 407, Issues 1–2, 3 September 2009, Pages 58-61
Clinica Chimica Acta

Alterations in serum adipocyte fatty acid binding protein and retinol binding protein-4 in normal pregnancy and preeclampsia

https://doi.org/10.1016/j.cca.2009.06.031Get rights and content

Abstract

Background

Preeclampsia, a pregnancy-specific complication occurring in the second half of human pregnancy and one of the leading causes for perinatal mortality and morbidity, is characterized by the onset of hypertension and proteinuria. We measured circulating adipocyte fatty acid binding protein (AFABP) and retinol binding protein-4 (RBP-4) in patients with preeclampsia.

Methods

Twenty-seven healthy non-pregnant women, 27 healthy pregnant women at third trimester and 26 women with preeclampsia were recruited and blood samples were taken. Concentrations of serum AFABP and RBP-4 were measured with ELISA.

Results

There were significant differences in serum AFABP (median: 0.99, 0.93 and 1.81 ng/ml, respectively, P < 0.001) and RBP-4 (mean: 3.16, 2.65 and 4.27 ng/ml, respectively, P = 0.022) among non-pregnancy, normal pregnancy and preeclampsia. Serum AFABP was significantly higher in preeclampsia than non-pregnancy (P < 0.001) and normal pregnancy (P = 0.001). Serum RBP-4 was significantly higher in preeclampsia than normal pregnancy (P = 0.007) but not non-pregnancy (P = 0.061). There were no significant differences in serum RBP-4 and AFABP between non-pregnancy and normal pregnancy. Serum RBP-4 was significantly higher in severe than mild preeclampsia (mean: 5.15 vs 2.84 ng/ml, P = 0.046). There was no significant difference in serum AFABP between mild and severe preeclampsia.

Conclusion

Increased circulating AFABP and RBP-4 concentrations were demonstrated, suggesting it be an important pathophysiology of preeclampsia.

Introduction

The etiology of preeclampsia remains elusive although much has been achieved in understanding the pathophysiology and pathogenesis of preeclampsia in the recent years [1], [2]. Insulin resistance is among the fields that attracted much attention and is one of the most important pathophysiologies in preeclampsia [1], [2].

Pregnancy is a state of physiological insulin resistance. This state reaches maximal in the third trimester and is exacerbated in preeclampsia [3], [4]. Since insulin resistance progresses as placenta develops, insulin resistance has been considered the result of combination of placental factors including human placental lactogen, prolactin, insulin-like growth hormones and steroid hormones [5], [6], [7], [8]. However, adipokines have been proposed to take a role in the insulin resistance during pregnancy and in preeclampsia.

Adipokines, adipocyte-derived hormones that regulate metabolism, include adiponectin, leptin, resistin and visfatin, and are found expressed in human placentas [9], [10]. These hormones are proposed involved in the pathogenesis of preeclampsia by regulating metabolism and by affecting insulin sensitivity [10]. The appearance of novel adipokines enhanced our understandings in the role of adipokines in maintaining insulin resistance during pregnancy and in the development of preeclampsia.

Both adipocyte fatty acid binding protein (AFABP, also known as FABP-4 or aP2) and retinol binding protein-4 (RBP-4) have been described as novel adipokines associated with insulin resistance, overweight and obesity [11], [12], [13]. Serum RBP4 concentration was elevated in insulin-resistant mice and humans with obesity and type-2 diabetes mellitus (T2DM) and over-expression of RBP4 causes insulin resistance and normalization of serum RBP4 concentration improve insulin resistance and glucose intolerance in mice [11]. The concentration of AFABP in circulation was significantly increased in obese subjects compared with lean control and was correlated positively with waist circumference, insulin resistance, blood pressure [12] and atherogenic dyslipidemia in diabetic subjects [14]. Higher concentration of circulating AFABP predicted the increased risk for metabolic syndrome, T2DM and cardiovascular diseases [13].

Due to the close link with insulin resistance, the changes of RBP4 and AFABP in gestational diabetes, a pregnancy complication characterized by insulin resistance, attracted attention of pioneer researchers. However, publication regarding the alterations of RBP4 and AFABP in preeclampsia is little. To obtain insight into the significance of RBP4 and AFABP in normal pregnancy and in preeclampsia, we determined the concentrations of RBP4 and AFABP in serum of preeclamptic women, controls of normal pregnancy and non-pregnant controls.

Section snippets

Subjects

Twenty-seven healthy non-pregnant women, 27 healthy pregnant women at third trimester and 26 women with preeclampsia were included. Women with preeclampsia were consecutively recruited in our hospital and healthy pregnant women were selected in the obstetrics clinic according to their age and gestational age. Non-pregnant women were healthy volunteers whose age was comparable. Among the preeclamptic women, 16 were diagnosed with severe preeclampsia and 10 mild. All subjects were nulliparous

Results

As shown in Table 1, there was no significant difference in maternal age among non-pregnant women, women with normal pregnancy and women with preeclampsia. There was no significant difference in gestational age between preeclampsia and normal pregnancy. The body mass index (BMI) was significantly different among the three groups (P < 0.001). The means of BMI were significantly different between non-pregnancy and normal pregnancy (P < 0.001), between non-pregnancy and preeclampsia (P < 0.001), but not

Discussion

We demonstrated that circulating concentrations of RBP-4 and AFABP were increased in preeclamptic women compared with control and that the concentrations of RBP-4 and AFABP were not significantly changed in late pregnancy compared with non-pregnant subjects. In addition, we noticed that, in contrast to mild preeclampsia, serum concentration of RBP-4 was significantly increased in severe preeclampsia, implying its relationship with disease severity.

The second half of normal pregnancy is a state

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