Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Pediatrics

The effects of NAMPT haplotypes and metabolic risk factors on circulating visfatin/NAMPT levels in childhood obesity

Abstract

Objective:

Polymorphisms in the NAMPT gene, which encodes the adipocytokine visfatin/nicotinamide phosphorybosil transferase (NAMPT), affect the circulating visfatin/NAMPT levels and are associated with obesity and cardiovascular diseases. However, no study has tested the hypothesis that NAMPT haplotypes could affect visfatin/NAMPT levels in case of childhood obesity. We investigated the effects of traditional metabolic risk factors (MRFs) and NAMPT polymorphisms T/C (rs1319501) and A/G (rs3801266) or haplotypes on visfatin/NAMPT levels in obese children and adolescents, and whether NAMPT polymorphisms and/or haplotypes are associated with susceptibility to childhood obesity.

Methods:

We studied 175 control, 99 obese and 82 obese with 3 MRFs children and adolescents. Genotypes were determined by a Taqman allele discrimination assay and real-time PCR. The plasma visfatin/NAMPT level was measured using an enzyme immunoassay.

Results:

Obese children and adolescents with 3 MRFs had higher plasma visfatin/NAMPT levels in comparison with control children and adolescents (P<0.05). Although positive associations were observed between visfatin/NAMPT and body mass index (rs=0.157; P=0.034) as well as visfatin/NAMPT and waist circumference (rs=0.192; P=0.011), visfatin/NAMPT and high-density lipoprotein cholesterol were inversely associated (rs=−0.162; P=0.031). No significant differences in genotype, allele or haplotype frequency distributions for the studied polymorphisms were found when the three groups were compared. However, higher plasma visfatin/NAMPT levels were found in control and obese subjects carrying the GG genotype for the A/G (rs3801266) polymorphism (P<0.05) but not in obese children with 3 MRFs. Moreover, control subjects carrying the ‘T-G’ haplotype showed higher plasma visfatin/NAMPT levels. NAMPT genotypes or haplotypes were not associated with childhood obesity.

Conclusions:

Obesity in children with 3 MRFs increases plasma visfatin/NAMPT levels, and this marker was associated with body mass index and waist circumference. The A/G polymorphism and NAMPT haplotypes affect plasma visfatin/NAMPT levels in controls but not in obese children with 3 MRFs. These results suggest that obesity and MRFs are more influential than genetic polymorphisms in the determination of visfatin/NAMPT levels in obese children. Further research is necessary to explain why the GG genotype is not associated with increased visfatin/NAMPT levels in obese children with 3 MRFs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2

Similar content being viewed by others

References

  1. Ahima RS, Flier JS . Adipose tissue as an endocrine organ. J Clin Endocrinol Metab 2000; 11: 327–332.

    CAS  Google Scholar 

  2. Libby P, Ridker PM, Maseri A . Inflammation and atherosclerosis. Circulation 2002; 105: 1135–1143.

    Article  CAS  Google Scholar 

  3. Van Gaal LF, Mertens IL, De Block CE . Mechanisms linking obesity with cardiovascular disease. Nature 2006; 444: 875–880.

    Article  CAS  Google Scholar 

  4. Fukuhara A, Matsuda M, Nishizawa M, Segawa K, Tanaka M, Kishimoto K et al. Visfatin: a protein secreted by visceral fat that mimics the effects of insulin. Science 2005; 307: 426–430.

    Article  CAS  Google Scholar 

  5. Dahl TB, Holm S, Aukrust P, Halvorsen B . Visfatin/NAMPT: a multifaceted molecule with diverse roles in physiology and pathophysiology. Annu Rev Nutr 2012; 32: 229–243.

    Article  CAS  Google Scholar 

  6. Saddi-Rosa P, Oliveira CS, Giuffrida FM, Reis AF . Visfatin, glucose metabolism and vascular disease: a review of evidence. Diabetol Metab Syndr 2010; 2: 21.

    Article  Google Scholar 

  7. Dahl TB, Yndestad A, Skjelland M, Oie E, Dahl A, Michelsen A et al. Increased expression of visfatin in macrophages of human unstable carotid and coronary atherosclerosis: possible role in inflammation and plaque destabilization. Circulation 2007; 115: 972–980.

    Article  CAS  Google Scholar 

  8. Adya R, Tan BK, Punn A, Chen J, Randeva HS . Visfatin induces human endothelial VEGF and MMP-2/9 production via MAPK and PI3K/Akt signalling pathways: novel insights into visfatin-induced angiogenesis. Cardiovasc Res 2008; 78: 356–365.

    Article  CAS  Google Scholar 

  9. Belo VA, Luizon MR, Carneiro PC, Gomes VA, Lacchini R, Lanna CM et al. Effect of metabolic syndrome risk factors and MMP-2 genetic variations on circulating MMP-2 levels in childhood obesity. Mol Biol Rep 2013; 40: 2697–2704.

    Article  CAS  Google Scholar 

  10. Belo VA, Souza-Costa DC, Lana CM, Caputo FL, Marcaccini AM, Gerlach RF et al. Assessment of matrix metalloproteinase (MMP)-2, MMP-8, MMP-9, and their inhibitors, the tissue inhibitors of metalloproteinase (TIMP)-1 and TIMP-2 in obese children and adolescents. Clin Biochem 2009; 42: 984–990.

    Article  CAS  Google Scholar 

  11. Belo VA, Souza-Costa DC, Luizon MR, Lanna CM, Carneiro PC, Izidoro-Toledo TC et al. Matrix metalloproteinase-9 genetic variations affect MMP-9 levels in obese children. Int J Obes (Lond) 2012; 36: 69–75.

    Article  CAS  Google Scholar 

  12. Belo VA, Souza-Costa DC, Luizon MR, Izidoro-Toledo TC, Lanna CM, Pinheiro LC et al. Vascular endothelial growth factor haplotypes associated with childhood obesity. DNA Cell Biol 2011; 30: 709–714.

    Article  CAS  Google Scholar 

  13. Berndt J, Kloting N, Kralisch S, Kovacs P, Fasshauer M, Schon MR et al. Plasma visfatin concentrations and fat depot-specific mRNA expression in humans. Diabetes 2005; 54: 2911–2916.

    Article  CAS  Google Scholar 

  14. Haider DG, Holzer G, Schaller G, Weghuber D, Widhalm K, Wagner O et al. The adipokine visfatin is markedly elevated in obese children. J Pediatr Gastroenterol Nutr 2006; 43: 548–549.

    Article  CAS  Google Scholar 

  15. Haider DG, Schindler K, Schaller G, Prager G, Wolzt M, Ludvik B . Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. J Clin Endocrinol Metab 2006; 91: 1578–1581.

    Article  CAS  Google Scholar 

  16. Chang YH, Chang DM, Lin KC, Shin SJ, Lee YJ . Visfatin in overweight/obesity, type 2 diabetes mellitus, insulin resistance, metabolic syndrome and cardiovascular diseases: a meta-analysis and systemic review. Diabetes Metab Res Rev 2011; 27: 515–527.

    Article  Google Scholar 

  17. Krzystek-Korpacka M, Patryn E, Bednarz-Misa I, Hotowy K, Noczynska A . Visfatin in juvenile obesity—the effect of obesity intervention and sex. Eur J Clin Invest 2011; 41: 1284–1291.

    Article  CAS  Google Scholar 

  18. Araki S, Dobashi K, Kubo K, Kawagoe R, Yamamoto Y, Kawada Y et al. Plasma visfatin concentration as a surrogate marker for visceral fat accumulation in obese children. Obesity (Silver Spring) 2008; 16: 384–388.

    Article  CAS  Google Scholar 

  19. Davutoglu M, Ozkaya M, Guler E, Garipardic M, Gursoy H, Karabiber H et al. Plasma visfatin concentrations in childhood obesity: relationships with insulin resistance and anthropometric indices. Swiss Med Wkly 2009; 139: 22–27.

    PubMed  Google Scholar 

  20. Revollo JR, Korner A, Mills KF, Satoh A, Wang T, Garten A et al. Nampt/PBEF/Visfatin regulates insulin secretion in beta cells as a systemic NAD biosynthetic enzyme. Cell Metab 2007; 6: 363–375.

    Article  CAS  Google Scholar 

  21. Haider DG, Schaller G, Kapiotis S, Maier C, Luger A, Wolzt M . The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia 2006; 49: 1909–1914.

    Article  CAS  Google Scholar 

  22. Lopez-Bermejo A, Chico-Julia B, Fernandez-Balsells M, Recasens M, Esteve E, Casamitjana R et al. Serum visfatin increases with progressive beta-cell deterioration. Diabetes 2006; 55: 2871–2875.

    Article  CAS  Google Scholar 

  23. Chen MP, Chung FM, Chang DM, Tsai JC, Huang HF, Shin SJ 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: 295–299.

    Article  CAS  Google Scholar 

  24. Dogru T, Sonmez A, Tasci I, Bozoglu E, Yilmaz MI, Genc H 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: 24–29.

    Article  CAS  Google Scholar 

  25. Lan J, Chen X, Wang S, Zhang X, Wu K, He S et al. The relationship between visfatin and HOMA-IR in hypertensive patients, and the effect of antihypertensive drugs on visfatin and HOMA-IR in hypertensive patients with insulin resistance. Diabetes Res Clin Pract 2011; 94: 71–76.

    Article  CAS  Google Scholar 

  26. Bailey SD, Loredo-Osti JC, Lepage P, Faith J, Fontaine J, Desbiens KM et al. Common polymorphisms in the promoter of the visfatin gene (PBEF1) influence plasma insulin levels in a French-Canadian population. Diabetes 2006; 55: 2896–2902.

    Article  CAS  Google Scholar 

  27. Gunes F, Akbal E, Cakir E, Akyurek O, Altunbas M, Ozbek M . Visfatin may be a novel marker for identifying stages of essential hypertension in advanced age patients. Intern Med 2012; 51: 553–557.

    Article  CAS  Google Scholar 

  28. Dogru T, Sonmez A, Tasci I, Yilmaz MI, Erdem G, Erturk H et al. Plasma visfatin levels in young male patients with uncomplicated and newly diagnosed hypertension. J Hum Hypertens 2007; 21: 173–175.

    Article  CAS  Google Scholar 

  29. Zhong M, Tan HW, Gong HP, Wang SF, Zhang Y, Zhang W . Increased serum visfatin in patients with metabolic syndrome and carotid atherosclerosis. Clin Endocrinol (Oxf) 2008; 69: 878–884.

    Article  CAS  Google Scholar 

  30. Kim SR, Bae YH, Bae SK, Choi KS, Yoon KH, Koo TH et al. Visfatin enhances ICAM-1 and VCAM-1 expression through ROS-dependent NF-kappaB activation in endothelial cells. Biochim Biophys Acta 2008; 1783: 886–895.

    Article  CAS  Google Scholar 

  31. Liu SW, Qiao SB, Yuan JS, Liu DQ . Association of plasma visfatin levels with inflammation, atherosclerosis and acute coronary syndromes (ACS) in humans. Clin Endocrinol (Oxf) 2009; 71: 202–207.

    Article  CAS  Google Scholar 

  32. Taskesen D, Kirel B, Us T . Serum visfatin levels, adiposity and glucose metabolism in obese adolescents. J Clin Res Pediatr Endocrinol 2012; 4: 76–81.

    Article  Google Scholar 

  33. Ooi SQ, Chan RM, Poh LK, Loke KY, Heng CK, Chan YH et al. Visfatin and its genetic variants are associated with obesity-related morbidities and cardiometabolic risk in severely obese children. Pediatr Obes 2013. e-pub ahead of print 28 February 2013 doi:10.1111/j.2047-6310.2013.00149.x.

    Article  Google Scholar 

  34. Crawford DC, Nickerson DA . Definition and clinical importance of haplotypes. Annu Rev Med 2005; 56: 303–320.

    Article  CAS  Google Scholar 

  35. Leander K, Gigante B, Silveira A, Vikstrom M, Hamsten A, Hogberg J . NAMPT (visfatin) and AKT1 genetic variants associate with myocardial infarction. Clin Chim Acta 2012; 413: 727–732.

    Article  CAS  Google Scholar 

  36. Tabassum R, Mahendran Y, Dwivedi OP, Chauhan G, Ghosh S, Marwaha RK et al. Common variants of IL6, LEPR, and PBEF1 are associated with obesity in Indian children. Diabetes 2012; 61: 626–631.

    Article  CAS  Google Scholar 

  37. Kuczmarski RJ, Ogden CL, Grummer-Strawn LM, Flegal KM, Guo SS, Wei R et al. CDC growth charts: United States. Adv Data 2000; 8: 1–27.

    Google Scholar 

  38. Update on the 1987 Task Force Report on High Blood Pressure in Children and Adolescents: a working group report from the National High Blood Pressure Education Program. National High Blood Pressure Education Program Working Group on Hypertension Control in Children and Adolescents. Pediatrics 1996; 98: 649–658.

  39. Cook S, Weitzman M, Auinger P, Nguyen M, Dietz WH . Prevalence of a metabolic syndrome phenotype in adolescents: findings from the third National Health and Nutrition Examination Survey, 1988-1994. Arch Pediatr Adolesc Med 2003; 157: 821–827.

    Article  Google Scholar 

  40. Weiss R, Dziura J, Burgert TS, Tamborlane WV, Taksali SE, Yeckel CW et al. Obesity and the metabolic syndrome in children and adolescents. N Engl J Med 2004; 350: 2362–2374.

    Article  CAS  Google Scholar 

  41. Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C . Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 2005; 115: e500–e503.

    Article  Google Scholar 

  42. Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC . Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412–419.

    Article  CAS  Google Scholar 

  43. Stephens M, Smith NJ, Donnelly P . A new statistical method for haplotype reconstruction from population data. Am J Hum Genet 2001; 68: 978–989.

    Article  CAS  Google Scholar 

  44. Curat CA, Wegner V, Sengenes C, Miranville A, Tonus C, Busse R et al. Macrophages in human visceral adipose tissue: increased accumulation in obesity and a source of resistin and visfatin. Diabetologia 2006; 49: 744–747.

    Article  CAS  Google Scholar 

  45. Kolsgaard ML, Wangensteen T, Brunborg C, Joner G, Holven KB, Halvorsen B et al. Elevated visfatin levels in overweight and obese children and adolescents with metabolic syndrome. Scand J Clin Lab Invest 2009; 69: 858–864.

    Article  CAS  Google Scholar 

  46. Jin H, Jiang B, Tang J, Lu W, Wang W, Zhou L et al. Serum visfatin concentrations in obese adolescents and its correlation with age and high-density lipoprotein cholesterol. Diabetes Res Clin Pract 2008; 79: 412–418.

    Article  CAS  Google Scholar 

  47. Korner A, Garten A, Bluher M, Tauscher R, Kratzsch J, Kiess W . Molecular characteristics of serum visfatin and differential detection by immunoassays. J Clin Endocrinol Metab 2007; 92: 4783–4791.

    Article  Google Scholar 

  48. Wang LS, Yan JJ, Tang NP, Zhu J, Wang YS, Wang QM et al. A polymorphism in the visfatin gene promoter is related to decreased plasma levels of inflammatory markers in patients with coronary artery disease. Mol Biol Rep 2010; 38: 819–825.

    Article  Google Scholar 

Download references

Acknowledgements

This study was funded by Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP-Brazil) and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq-Brazil).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J E Tanus-Santos.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Belo, V., Luizon, M., Lacchini, R. et al. The effects of NAMPT haplotypes and metabolic risk factors on circulating visfatin/NAMPT levels in childhood obesity. Int J Obes 39, 130–135 (2015). https://doi.org/10.1038/ijo.2013.173

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2013.173

Keywords

This article is cited by

Search

Quick links