Association of Adipocytokines: Resistin and Retinol Binding Protein-4 with Severity of Preeclampsia and Insulin Resistance

Abeer A. EL-Refai^{1, 2}, Sameer H. Fatani¹ and Hala F. M. Kamel^{1, 3,}

¹Biochemistry Department, Faculty of medicine, Umm Al-Qura University (UQU), Makkha, KSA

²Biochemistry Department, Faculty of medicine, Monufia University (MU), Shibeen Al-Koom, Egypt

³Medical Biochemistry Department, Faculty of Medicine, Ain Shams University (ASU), Cairo, Egypt

Cite this paper:
Abeer A. EL-Refai, Sameer H. Fatani and Hala F. M. Kamel. Association of Adipocytokines: Resistin and Retinol Binding Protein-4 with Severity of Preeclampsia and Insulin Resistance. American Journal of Medical and Biological Research. 2014; 2(3):76-82. doi: 10.12691/ajmbr-2-3-2

Abstract

Dysregulation of maternal circulating adipocytokines has been implicated in several obstetrical syndromes including preeclampsia (PE). It has been suggested that adipocytokines provide a molecular link between metabolic derangements and inflammatory response in complicated pregnancies. We aimed in this study to evaluate the relationship between serum levels of Retinol binding protein-4 (RBP-4) and Resistin with clinical, anthropometric and metabolic parameters of PE. This study included 3 groups: group 1 included 50 pregnant females with PE, group 2 included 50 healthy pregnant females and group 3 included 50 healthy non-pregnant female as a control group. For all groups anthropometric and clinical measurements were performed. Serum RBP-4, resistin, insulin were measured by ELISA and Insulin resistance was calculated by Hemostasis model assessment index (HOMA-IR). Our results showed that serum RBP-4 and resistin concentrations were elevated in PE [39(33.25-40.87) ug/ml] & [61(23.5-91.87) ng/ml] compared to normal pregnancy [18.5(8-27.87) ug/ml] & [25.5(12.7-49.12) ng/ml). Moreover, RBP4 but not resistin levels were elevated in severe cases relative to mild cases of PE. Serum levels of RBP4 showed positive significant correlation with [SBP (r=0.38, p= 0.001) & DBP (r=0.32, p=0.01)] which are markers of severity. Fasting insulin was positively correlated with RBP-4 (p=0.04). By multiple linear regression analysis, serum RBP-4 levels were significantly and positively correlated with SBP (P=0.01), while markers of adiposity were not independently associated with resistin. Conclusion: RBP-4 and resistin were up-regulated in PE, furthermore RBP-4 not resistin levels were independently associated with markers of severity of PE. However no clear relationship were observed between HOMA-IR with both RBP-4 and resistin and the role of Insulin resistance in PE was not clearly proved.

Keywords:
preeclampsia Resistin Retinol binding protein-4 HOMA-IR

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

References:

[1]	Valensise H, Vasapollo B, Gagliardi G and Novelli GP. Early and late preeclampsia: "Two different maternal hemodynamic states in the latent phase of the disease". Hypertension: (2008) 52; 873-880.
[2]	Carty D, Delles C and Dominiczak A. Preeclampsia and future maternal health. J Hypertens. (2010): 28; 1349-1355.
[3]	Cudihy D and Lee V. The pathophysiology of pre-eclampsia. Journal of Obstetrics and Gynaecology. (2009): 29; 576-582.
[4]	Masuyama H, Inou S and Hiramatsu Y. RBP-4 and insulin resistance in preeclampsia. Endocrine Journal. (2011): 58; 47-53.
[5]	Miehle K, Stepan H and Fasshauer m. Leptin, adiponectin and other adipokines in gestational diabetes mellitus and pre-eclampsia: Clinical Endocrinology. (2012): 76; 2-11.
[6]	Gao J, Chang Chua C, Chen Z, Wang H, Xu X and Hamdy R. Resistin, an adipocytokine, offers protection against acute myocardial infarction. J Mol Cell Cardiol (2007): 43; 601-9.
[7]	Ippolito D, Tersigni C, Scambia G, and Di Simone N. Adipokines, an adipose tissue and placental product with biological functions during pregnancy. International Union of Biochemistry and Molecular Biology. (2012): 38; 14-23.
[8]	Kusminski C, da Silva N, Creely S, Fisher F, Harte A, Baker A, Kumar S and McTernan P. The in vitro effects of resistin on the innate immune signaling pathway in isolated human subcutaneous adipocytes. J Clin endocrinol Metab. (2007): 92; 270-276.
[9]	Nanda S, Poon L, Muhaisen M, Acosta I and Nicolaides K. Maternal serum resistin at 11 to 13 weeks' gestation in normal and pathological pregnancies. Metabolism clinical and experimental. (2012): 699-705.
[10]	Yang Q, Graham T and Mody N. Serum RBP-4 contributes to insulin resistance in obesity and type 2 diabetes. Nature. (2005): 436; 356-62.
[11]	Ku Y, Han K, Ahn H, Kwon H, Koo B, Kim H and Min K. Resistance exercise did not alter intramuscular adipose tissue but reduced RBP-4 concentration in individuals with type 2 diabetes mellitus. Journal of International Medical Research. (2010): 38; 782-791.
[12]	Graham T, Yang Q, Bluher M, Hammarstedt A, Ciaraldi T, Henry R, Wason C, Oberbach A, Jansson P, Smith U and Kahn B. RBP-4 and insulin resistance in lean, obese, and diabetic subjects. New England Journal of Medicine. (2011): 354; 2552-2563.
[13]	Judzewitsch R, Pfeifer M, Best J, Beard J, Halter J and Porte D. Chronic Chlorpropamide therapy of noninsulin-dependent diabetes augments basal and stimulated insulin secretion by increasing islet sensitivity to glucose. J. Clin. End. and Metab. (1982): 55; 321-328.
[14]	Shirai K. Obesity as the core of the metabolic syndrome and the management of coronary heart disease. Curr. Med. Res. Opin. (2004): 20; 295-304.
[15]	Schaffler A, Buchler C and Muller-Lander U. Identification of variables influencing resistin serum levels in patients with type 1 and type 2 diabetes mellitus. (2004): 36; 702-7.
[16]	Mody N. Am. J. Physiol Endocrinol Metab. (2008): 294; 785-793.
[17]	Stephan H, Ebert T, Schrey S, Reisenbüchler C, Blüher M, Stumvoll M, Kratzsch J, Tönnessen P, Faber R and Fasshauer M. Preliminary report: Serum levels of RBP-4 in preeclampsia. Metabolism. (2009): 58; 275-277.
[18]	Zavalza-Gómez A, Anaya-Prado R, Rincón-Sánchez A and Mora-Martínez J Adipokines and insulin resistance during pregnancy Diabetes Res Clin Pract. (2008): 80; 8-15.
[19]	Patel L, Buckels A and Kinghorn I. Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators. Biochem Biophys Res Commun. (2003): 300; 472-6.
[20]	Seol H, Yeo M, Kim A, Lee E, and Kim H. Comparison of Serum Levels and the Placental Expression of Resistin Between Patients with Preeclampsia and Normal Pregnant Women. Hypertension in Pregnancy. (2010): 29; 310-317.
[21]	Haugen F, Ranheim T, Harsem N, Lips E, Staff A and Drevon C. Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression. Am J Physiol Endocrinol Metab. (2006); 290; 326-333.
[22]	Redman C and Sargent I. Latest advances in understanding preeclampsia. Science. (2005): 308; 1592-1594.
[23]	Sibai B. Preeclampsia: an inflammatory syndrome? Am J Obstet Gynecol (2004): 191; 1061-1062.
[24]	Savage D, Sewter C, Klenk E, Segal D, Vidal-Puig A, Considine R and O’Rahilly S. Resistin/ Fizz3 expression in relation to obesity and peroxisome proliferator-activated receptorgamma action in humans. Diabetes. (2001): 50; 2199-2202.
[25]	Yao-Borengasser A, Varma V, Bodles A, Rasouli N, Phanavanh B and Lee M. RBP-4 expression in humans: relationship to insulin resistance, inflammation, and response to pioglitazone. J Clin Endocrinol Metab. (2007); 92; 2590-2597.
[26]	Inoue S, Takamoto N and Akahori. Elevated level of serum RBP-4 in pregnancy-induced hypertension. J Obstet Gynaecol Res. (2009): 35; 293-300.
[27]	Shangguan X, Liu F, Wang H, He J and Dong M. Alterations in serum adipocyte fatty acid binding protein and retinol binding protein-4 in normal pregnancy and preeclampsia. Clinica Chimica Acta. (2009): 407; 58-61.
[28]	Vaisbuch E, Romero R, Mazaki-Tovi S, Erez O and Kwon Kim S. RBP-4-A Novel Association with Early-Onset Preeclampsia. J Perinat Med. (2010): 38; 129-139.
[29]	Atkinson K, Blumenstein M, Black M, Wu S, Kasabov N and Taylor R. An altered pattern of circulating apolipoprotein E3 isoforms is implicated in preeclampsia. J Lipid Res. (2009): 50; 71-80.
[30]	Al-Kholy A, Abadier M, Rageh E and El-Kallaf H. Serum levels of placental growth factor and retinol-binding protein-4 in pregnancy-induced hypertensive women. ScienceJournal of American. (2010): 6:12.
[31]	Solini A, Santini E, Madec S, Rossi C and Muscelli E. RBP-4 in women with untreated essential hypertension. Am J Hypertens. (2009): 22; 1001-6.
[32]	Qi Q. Elevated RBP-4 levels are associated with metabolic syndrome in Chinese people. J. Clin. Endocrinol. Metab. (2007): 92; 4827-34.
[33]	Ingelsson E, Sundstrom J, Melhus H, Michaelsson K, Berne C, Vasan R, Riserus U, Blomhoff R, Lind L and Arnlov J. Circulating retinol-binding protein 4, cardiovascular risk factors and prevalent cardiovascular disease in elderly. Atherosclerosis. (2009): 206; 38-39.
[34]	Chiba M, Saitoh S, Ohnishi H, Akasaka H, Mitsumata K, Furukawa T, and Shimamoto K. Associations of metabolic factors, especially serum (RBP4), with blood pressure in Japanese. Endocr J. (2010): 57: 811-7.
[35]	Potenza M, Marasciulo F and Chieppa D. Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production. Am J Physiol Heart Circ Physiol. (2005): 289; 813-822.
[36]	Cheng X and Zhang H. Serum RBP-4 is positively related to insulin resistance in Chinese subjects with type 2 diabetes. Diabetes Res Clin Pract. (2009): 84 (1); 58-60.
[37]	Henze A, Frey S, Raila J, Tepel M, Scholze A and Pfeiffer A. Evidence that kidney function but not type 2 diabetes determines RBP-4 serum levels. Diabetes. (2009): 57; 3323-3326.
[38]	Cabre A, Lazaro I, Girona J, Manzanares A, Plana N and Heras M. RBP-4 as a plasma biomarker of renal dysfunction and cardiovascular disease. J Intern Med. (2007): 262; 496-503.
[39]	Frey S, Henze A and Nagl B. Effect of renal replacement therapy on RBP-4 isoforms. Clin Chim Acta. (2009): 401; 46-50.