The Role of Nicotinamide Phosphoribosyltransferase in Pregnancy: A Review

Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) was first reported in 1994 and has been explored in various human disease processes. However, until recently, very little has been done to define the role of NAMPT in pregnancy. NAMPT is a 52 kDa protein that has diverse functions in the human body, acting as a growth factor, cytokine, an enzyme, and an insulinomimetic agent. Initial studies examined NAMPT expression in fetal membranes and its effects on the amnion. Later research in nonpregnant studies showed an insulinomimetic effect, and attention focused on its role in gestational diabetes. In addition, as studies revealed NAMPT's function as an inflammatory cytokine, studies examined NAMPT in preeclampsia and fetal growth restriction. Several studies have confirmed that NAMPT is a marker of systemic infectious processes such as pyelonephritis and intrauterine infection. In this review, we present the current understanding of NAMPT's role in various pregnancy-related conditions as well as possible directions for future research.

Keywords

NAMPT - visfatin - pre-B-cell colony-enhancing factor - pregnancy - diabetes - preeclampsia - gestational diabetes - adipokine

Note

The authors have no disclosure of any financial support received for the work being published.

• References

• 1 Samal B, Sun Y, Stearns G, Xie C, Suggs S, McNiece I. Cloning and characterization of the cDNA encoding a novel human pre-B-cell colony-enhancing factor. Mol Cell Biol 1994; 14 (2) 1431-1437
• 2 Zhang LQ, Heruth DP, Ye SQ. Nicotinamide phosphoribosyltransferase in human diseases. J Bioanal Biomed 2011; 3: 13-25
• 3 Fukuhara A, Matsuda M, Nishizawa M , et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 2005; 307 (5708) 426-430
• 4 Mazaki-Tovi S, Romero R, Kusanovic JP , et al. Maternal visfatin concentration in normal pregnancy. J Perinat Med 2009; 37 (3) 206-217
• 5 Zhou J, Seidel ER. Estrogens induce visfatin expression in 3T3-L1 cells. Peptides 2010; 31 (2) 271-274
• 6 Zulfikaroglu E, Isman F, Payasli A, Kilic S, Kucur M, Danisman N. Plasma visfatin levels in preeclamptic and normal pregnancies. Arch Gynecol Obstet 2010; 281 (6) 995-998
• 7 Szamatowicz J, Kuźmicki M, Telejko B , et al. Serum visfatin concentration is elevated in pregnant women irrespectively of the presence of gestational diabetes. Ginekol Pol 2009; 80 (1) 14-18
• 8 Morgan SA, Bringolf JB, Seidel ER. Visfatin expression is elevated in normal human pregnancy. Peptides 2008; 29 (8) 1382-1389
• 9 Ognjanovic S, Bryant-Greenwood GD. Pre-B-cell colony-enhancing factor, a novel cytokine of human fetal membranes. Am J Obstet Gynecol 2002; 187 (4) 1051-1058
• 10 Kendal-Wright CE. Stretching, mechanotransduction, and proinflammatory cytokines in the fetal membranes. Reprod Sci 2007; 14 (8, Suppl): 35-41
• 11 Ma Y, Cheng Y, Wang J, Cheng H, Zhou S, Li X. The changes of visfatin in serum and its expression in fat and placental tissue in pregnant women with gestational diabetes. Diabetes Res Clin Pract 2010; 90 (1) 60-65
• 12 Luo JX, Liu XH, Zhang L, He GL. [The expression of visfatin in placenta in women with gestational diabetes mellitus]. Sichuan Da Xue Xue Bao Yi Xue Ban 2011; 42 (2) 204-207
• 13 Mazaki-Tovi S, Vaisbuch E, Romero R , et al. Maternal and neonatal circulating visfatin concentrations in patients with pre-eclampsia and a small-for-gestational age neonate. J Matern Fetal Neonatal Med 2010; 23 (10) 1119-1128
• 14 Fukuhara A, Matsuda M, Nishizawa M , et al. Retraction. Science 2007; 318 (5850) 565
• 15 Xie H, Tang S-Y, Luo X-H , et al. Insulin-like effects of visfatin on human osteoblasts. Calcif Tissue Int 2007; 80 (3) 201-210
• 16 Revollo JR, Körner A, Mills KF , et al. NAMPT/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 2007; 6 (5) 363-375
• 17 Berndt J, Klöting N, Kralisch S , et al. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 2005; 54 (10) 2911-2916
• 18 Chen M-P, Chung F-M, Chang D-M , et al. Elevated plasma level of visfatin/pre-B cell colony-enhancing factor in patients with type 2 diabetes mellitus. J Clin Endocrinol Metab 2006; 91 (1) 295-299
• 19 Dogru T, Sonmez A, Tasci I , et al. Plasma visfatin levels in patients with newly diagnosed and untreated type 2 diabetes mellitus and impaired glucose tolerance. Diabetes Res Clin Pract 2007; 76 (1) 24-29
• 20 Sandeep S, Velmurugan K, Deepa R, Mohan V. Serum visfatin in relation to visceral fat, obesity, and type 2 diabetes mellitus in Asian Indians. Metabolism 2007; 56 (4) 565-570
• 21 Alghasham AA, Barakat YA. Serum visfatin and its relation to insulin resistance and inflammation in type 2 diabetic patients with and without macroangiopathy. Saudi Med J 2008; 29 (2) 185-192
• 22 Botella-Carretero JI, Luque-Ramírez M, Alvarez-Blasco F, Peromingo R, San Millán JL, Escobar-Morreale HF. The increase in serum visfatin after bariatric surgery in morbidly obese women is modulated by weight loss, waist circumference, and presence or absence of diabetes before surgery. Obes Surg 2008; 18 (8) 1000-1006
• 23 Retnakaran R, Youn B-S, Liu Y , et al. Correlation of circulating full-length visfatin (PBEF/NAMPT) with metabolic parameters in subjects with and without diabetes: a cross-sectional study. Clin Endocrinol (Oxf) 2008; 69 (6) 885-893
• 24 Ziegelmeier M, Bachmann A, Seeger J , et al. Adipokines influencing metabolic and cardiovascular disease are differentially regulated in maintenance hemodialysis. Metabolism 2008; 57 (10) 1414-1421
• 25 Haider DG, Pleiner J, Francesconi M, Wiesinger GF, Müller M, Wolzt M. Exercise training lowers plasma visfatin concentrations in patients with type 1 diabetes. J Clin Endocrinol Metab 2006; 91 (11) 4702-4704
• 26 López-Bermejo A, Chico-Julià B, Fernàndez-Balsells M , et al. Serum visfatin increases with progressive beta-cell deterioration. Diabetes 2006; 55 (10) 2871-2875
• 27 Jian W-X, Luo T-H, Gu Y-Y , et al. The visfatin gene is associated with glucose and lipid metabolism in a Chinese population. Diabet Med 2006; 23 (9) 967-973
• 28 Palin M-F, Labrecque B, Beaudry D, Mayhue M, Bordignon V, Murphy BD. Visfatin expression is not associated with adipose tissue abundance in the porcine model. Domest Anim Endocrinol 2008; 35 (1) 58-73
• 29 Körner A, Garten A, Blüher M, Tauscher R, Kratzsch J, Kiess W. Molecular characteristics of serum visfatin and differential detection by immunoassays. J Clin Endocrinol Metab 2007; 92 (12) 4783-4791
• 30 Takebayashi K, Suetsugu M, Wakabayashi S, Aso Y, Inukai T. Association between plasma visfatin and vascular endothelial function in patients with type 2 diabetes mellitus. Metabolism 2007; 56 (4) 451-458
• 31 Pagano C, Pilon C, Olivieri M , et al. Reduced plasma visfatin/pre-B cell colony-enhancing factor in obesity is not related to insulin resistance in humans. J Clin Endocrinol Metab 2006; 91 (8) 3165-3170
• 32 Fox EJ, Leeder JS, Ye SQ, Becker ML. Decreased expression of nicotinamide phosphoribosyltransferase in patients with juvenile idiopathic arthritis receiving methotrexate. J Rheumatol 2013; 40 (5) 741-742
• 33 Krzyzanowska K, Krugluger W, Mittermayer F , et al. Increased visfatin concentrations in women with gestational diabetes mellitus. Clin Sci (Lond) 2006; 110 (5) 605-609
• 34 Chan T-F, Chen Y-L, Lee C-H , et al. Decreased plasma visfatin concentrations in women with gestational diabetes mellitus. J Soc Gynecol Investig 2006; 13 (5) 364-367
• 35 Lewandowski KC, Stojanovic N, Press M , et al. Elevated serum levels of visfatin in gestational diabetes: a comparative study across various degrees of glucose tolerance. Diabetologia 2007; 50 (5) 1033-1037
• 36 Haider DG, Handisurya A, Storka A , et al. Visfatin response to glucose is reduced in women with gestational diabetes mellitus. Diabetes Care 2007; 30 (7) 1889-1891
• 37 Akturk M, Altinova AE, Mert I , et al. Visfatin concentration is decreased in women with gestational diabetes mellitus in the third trimester. J Endocrinol Invest 2008; 31 (7) 610-613
• 38 Mazaki-Tovi S, Romero R, Kusanovic JP , et al. Visfatin in human pregnancy: maternal gestational diabetes vis-à-vis neonatal birthweight. J Perinat Med 2009; 37 (3) 218-231
• 39 Telejko B, Kuzmicki M, Zonenberg A , et al. Visfatin in gestational diabetes: serum level and mRNA expression in fat and placental tissue. Diabetes Res Clin Pract 2009; 84 (1) 68-75
• 40 Coskun A, Ozkaya M, Kiran G, Kilinc M, Arikan DC. Plasma visfatin levels in pregnant women with normal glucose tolerance, gestational diabetes and pre-gestational diabetes mellitus. J Matern Fetal Neonatal Med 2010; 23 (9) 1014-1018
• 41 Gok DE, Yazici M, Uckaya G , et al. The role of visfatin in the pathogenesis of gestational diabetes mellitus. J Endocrinol Invest 2011; 34 (1) 3-7
• 42 Ferreira AFA, Rezende JC, Vaikousi E, Akolekar R, Nicolaides KH. Maternal serum visfatin at 11-13 weeks of gestation in gestational diabetes mellitus. Clin Chem 2011; 57 (4) 609-613
• 43 Rezvan N, Hosseinzadeh-Attar MJ, Masoudkabir F, Moini A, Janani L, Mazaherioun M. Serum visfatin concentrations in gestational diabetes mellitus and normal pregnancy. Arch Gynecol Obstet 2012; 285 (5) 1257-1262
• 44 Skvarca A, Tomazic M, Krhin B, Blagus R, Janez A. Adipocytokines and insulin resistance across various degrees of glucose tolerance in pregnancy. J Int Med Res 2012; 40 (2) 583-589
• 45 Kaygusuz I, Gumus II, Yılmaz S , et al. Serum levels of visfatin and possible interaction with iron parameters in gestational diabetes mellitus. Gynecol Obstet Invest 2013; 75 (3) 203-209
• 46 Liang Y, Xu X-M, Wang H-S, Wang P-W. [Correlation between the expression of gastrocolic omentum visfatin mRNA and gestational diabetes mellitus]. Zhonghua Fu Chan Ke Za Zhi 2008; 43 (11) 824-827
• 47 Mastorakos G, Valsamakis G, Papatheodorou DC , et al. The role of adipocytokines in insulin resistance in normal pregnancy: visfatin concentrations in early pregnancy predict insulin sensitivity. Clin Chem 2007; 53 (8) 1477-1483
• 48 Valsamakis G, Papatheodorou DC, Margeli A , et al. First trimester maternal BMI is a positive predictor of cord blood c-peptide levels while maternal visfatin levels is a negative predictor of birth weight. Hormones (Athens) 2014; 13 (1) 87-94
• 49 Briana DD, Boutsikou M, Gourgiotis D , et al. Role of visfatin, insulin-like growth factor-I and insulin in fetal growth. J Perinat Med 2007; 35 (4) 326-329
• 50 Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet 2005; 365 (9461) 785-799
• 51 McCarthy JF, Misra DN, Roberts JM. Maternal plasma leptin is increased in preeclampsia and positively correlates with fetal cord concentration. Am J Obstet Gynecol 1999; 180 (3 Pt 1) 731-736
• 52 Laivuori H, Kaaja R, Koistinen H , et al. Leptin during and after preeclamptic or normal pregnancy: its relation to serum insulin and insulin sensitivity. Metabolism 2000; 49 (2) 259-263
• 53 Laivuori H, Gallaher MJ, Collura L , et al. Relationships between maternal plasma leptin, placental leptin mRNA and protein in normal pregnancy, pre-eclampsia and intrauterine growth restriction without pre-eclampsia. Mol Hum Reprod 2006; 12 (9) 551-556
• 54 Teppa RJ, Ness RB, Crombleholme WR, Roberts JM. Free leptin is increased in normal pregnancy and further increased in preeclampsia. Metabolism 2000; 49 (8) 1043-1048
• 55 Ouyang Y, Chen H, Chen H. Reduced plasma adiponectin and elevated leptin in pre-eclampsia. Int J Gynaecol Obstet 2007; 98 (2) 110-114
• 56 Chappell LC, Seed PT, Briley A , et al. A longitudinal study of biochemical variables in women at risk of preeclampsia. Am J Obstet Gynecol 2002; 187 (1) 127-136
• 57 Hendler I, Blackwell SC, Mehta SH , et al. The levels of leptin, adiponectin, and resistin in normal weight, overweight, and obese pregnant women with and without preeclampsia. Am J Obstet Gynecol 2005; 193 (3 Pt 2) 979-983
• 58 Nakatsukasa H, Masuyama H, Takamoto N, Hiramatsu Y. Circulating leptin and angiogenic factors in preeclampsia patients. Endocr J 2008; 55 (3) 565-573
• 59 Bartha JL, Romero-Carmona R, Escobar-Llompart M, Comino-Delgado R. The relationships between leptin and inflammatory cytokines in women with pre-eclampsia. BJOG 2001; 108 (12) 1272-1276
• 60 Anim-Nyame N, Sooranna SR, Steer PJ, Johnson MR. Longitudinal analysis of maternal plasma leptin concentrations during normal pregnancy and pre-eclampsia. Hum Reprod 2000; 15 (9) 2033-2036
• 61 Poston L. Leptin and preeclampsia. Semin Reprod Med 2002; 20 (2) 131-138
• 62 Tommaselli GA, Pighetti M, Nasti A , et al. Serum leptin levels and uterine Doppler flow velocimetry at 20 weeks' gestation as markers for the development of pre-eclampsia. Gynecol Endocrinol 2004; 19 (3) 160-165
• 63 Haugen F, Ranheim T, Harsem NK, Lips E, Staff AC, Drevon CA. Increased plasma levels of adipokines in preeclampsia: relationship to placenta and adipose tissue gene expression. Am J Physiol Endocrinol Metab 2006; 290 (2) E326-E333
• 64 Kajantie E, Kaaja R, Ylikorkala O, Andersson S, Laivuori H. Adiponectin concentrations in maternal serum: elevated in preeclampsia but unrelated to insulin sensitivity. J Soc Gynecol Investig 2005; 12 (6) 433-439
• 65 Naruse K, Yamasaki M, Umekage H, Sado T, Sakamoto Y, Morikawa H. Peripheral blood concentrations of adiponectin, an adipocyte-specific plasma protein, in normal pregnancy and preeclampsia. J Reprod Immunol 2005; 65 (1) 65-75
• 66 Fasshauer M, Blüher M, Stumvoll M, Tönessen P, Faber R, Stepan H. Differential regulation of visfatin and adiponectin in pregnancies with normal and abnormal placental function. Clin Endocrinol (Oxf) 2007; 66 (3) 434-439
• 67 Hu W, Wang Z, Wang H, Huang H, Dong M. Serum visfatin levels in late pregnancy and pre-eclampsia. Acta Obstet Gynecol Scand 2008; 87 (4) 413-418
• 68 Fasshauer M, Waldeyer T, Seeger J , et al. Serum levels of the adipokine visfatin are increased in pre-eclampsia. Clin Endocrinol (Oxf) 2008; 69 (1) 69-73
• 69 Adali E, Yildizhan R, Kolusari A , et al. Increased visfatin and leptin in pregnancies complicated by pre-eclampsia. J Matern Fetal Neonatal Med 2009; 22 (10) 873-879
• 70 Briana DD, Malamitsi-Puchner A. Reviews: adipocytokines in normal and complicated pregnancies. Reprod Sci 2009; 16 (10) 921-937
• 71 American College of Obstetricians and Gynecologists. ACOG Practice bulletin no. 134: fetal growth restriction. Obstet Gynecol 2013; 121 (5) 1122-1133
• 72 Malamitsi-Puchner A, Briana DD, Boutsikou M, Kouskouni E, Hassiakos D, Gourgiotis D. Perinatal circulating visfatin levels in intrauterine growth restriction. Pediatrics 2007; 119 (6) e1314-e1318
• 73 Shang LX, Tang QL, Wang J , et al. [Relationship of adiponectin and visfatin with fetus intrauterine growth]. Zhonghua Fu Chan Ke Za Zhi 2009; 44 (4) 246-248
• 74 Mazaki-Tovi S, Romero R, Kim SK , et al. Could alterations in maternal plasma visfatin concentration participate in the phenotype definition of preeclampsia and SGA?. J Matern Fetal Neonatal Med 2010; 23 (8) 857-868
• 75 López-Bermejo A, de Zegher F, Díaz-Silva M, Vicente MP, Valls C, Ibáñez L. Cord serum visfatin at term birth: maternal smoking unmasks the relation to foetal growth. Clin Endocrinol (Oxf) 2008; 68 (1) 77-81
• 76 Nemeth E, Tashima LS, Yu Z, Bryant-Greenwood GD. Fetal membrane distention: I. Differentially expressed genes regulated by acute distention in amniotic epithelial (WISH) cells. Am J Obstet Gynecol 2000; 182 (1 Pt 1) 50-59
• 77 Ognjanovic S, Tashima LS, Bryant-Greenwood GD. The effects of pre-B-cell colony-enhancing factor on the human fetal membranes by microarray analysis. Am J Obstet Gynecol 2003; 189 (4) 1187-1195
• 78 Ye SQ, Simon BA, Maloney JP , et al. Pre-B-cell colony-enhancing factor as a potential novel biomarker in acute lung injury. Am J Respir Crit Care Med 2005; 171 (4) 361-370
• 79 Jia SH, Li Y, Parodo J , et al. Pre-B cell colony-enhancing factor inhibits neutrophil apoptosis in experimental inflammation and clinical sepsis. J Clin Invest 2004; 113 (9) 1318-1327
• 80 Brentano F, Schorr O, Ospelt C , et al. Pre-B cell colony-enhancing factor/visfatin, a new marker of inflammation in rheumatoid arthritis with proinflammatory and matrix-degrading activities. Arthritis Rheum 2007; 56 (9) 2829-2839
• 81 Tilg H, Moschen AR. Role of adiponectin and PBEF/visfatin as regulators of inflammation: involvement in obesity-associated diseases. Clin Sci (Lond) 2008; 114 (4) 275-288
• 82 Moschen AR, Geiger S, Gerner R, Tilg H. Pre-B cell colony enhancing factor/NAMPT/visfatin and its role in inflammation-related bone disease. Mutat Res 2010; 690 (1𠀓2) 95-101
• 83 Ognjanovic S, Ku TL, Bryant-Greenwood GD. Pre-B-cell colony-enhancing factor is a secreted cytokine-like protein from the human amniotic epithelium. Am J Obstet Gynecol 2005; 193 (1) 273-282
• 84 Kendal-Wright CE, Hubbard D, Bryant-Greenwood GD. Chronic stretching of amniotic epithelial cells increases pre-B cell colony-enhancing factor (PBEF/visfatin) expression and protects them from apoptosis. Placenta 2008; 29 (3) 255-265
• 85 Marvin KW, Keelan JA, Eykholt RL, Sato TA, Mitchell MD. Use of cDNA arrays to generate differential expression profiles for inflammatory genes in human gestational membranes delivered at term and preterm. Mol Hum Reprod 2002; 8 (4) 399-408
• 86 Mazaki-Tovi S, Romero R, Kusanovic JP , et al. Visfatin/pre-B cell colony-enhancing factor in amniotic fluid in normal pregnancy, spontaneous labor at term, preterm labor and prelabor rupture of membranes: an association with subclinical intrauterine infection in preterm parturition. J Perinat Med 2008; 36 (6) 485-496
• 87 Mazaki-Tovi S, Romero R, Vaisbuch E , et al. Maternal plasma visfatin in preterm labor. J Matern Fetal Neonatal Med 2009; 22 (8) 693-704
• 88 Mazaki-Tovi S, Vaisbuch E, Romero R , et al. Maternal plasma concentration of the pro-inflammatory adipokine pre-B-cell-enhancing factor (PBEF)/visfatin is elevated in pregnant patients with acute pyelonephritis. Am J Reprod Immunol 2010; 63 (3) 252-262
• 89 Norwitz ER, Robinson JN, Challis JR. The control of labor. N Engl J Med 1999; 341 (9) 660-666
• 90 Myers DA, Nathanielsz PW. Biologic basis of term and preterm labor. Clin Perinatol 1993; 20 (1) 9-28
• 91 Mazaki-Tovi S, Romero R, Vaisbuch E , et al. Evidence for differential regulation of the adipokine visfatin in the maternal and fetal compartments in normal spontaneous labor at term. J Perinat Med 2010; 38 (3) 281-288
• 92 Katwa LC, Seidel ER. Visfatin in pregnancy: proposed mechanism of peptide delivery. Amino Acids 2009; 37 (4) 555-558
• 93 Lappas M. Visfatin regulates the terminal processes of human labour and delivery via activation of the nuclear factor-κB pathway. Mol Cell Endocrinol 2012; 348 (1) 128-134