Skip to main content
SpringerLink
Log in

Plasma ghrelin levels and polymorphisms of ghrelin gene in Chinese obese children and adolescents

  • Original Article
  • Published:
Irish Journal of Medical Science Aims and scope Submit manuscript

Abstract

Aim

To evaluate the role of fasting plasma ghrelin levels [ln(ghrelin)] and polymorphisms of ghrelin gene in Chinese obese children.

Methods

Genotyping for ghrelin polymorphism was performed in 230 obese and 100 normal weight children. Among them, plasma ghrelin levels were measured in 91 obese and 23 health subjects.

Results

(1) Bivariate correlation analysis showed the ln(ghrelin) was inversely correlated with abnormality of glucose metabolism (r = −0.240, P = 0.023). Stepwise multiple regression analysis showed that abnormality of glucose metabolism was an independent determinant of plasma ghrelin levels (P = 0.023). (2) There was no difference in frequency of Leu72Met polymorphisms between obese and control groups (36.09 vs. 41.00%).

Conclusion

Ghrelin is associated with obesity in childhood, especially associated with the glucose homeostasis. Lower ghrelin levels might be a result of obesity, but not a cause of obesity. The Leu72Met polymorphism of ghrelin gene is not associated with obesity and metabolic syndrome in Chinese children.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Kojima M, Hosoda H, Date Y et al (1999) Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402:656–660. doi:10.1038/45230

    Article  CAS  PubMed  Google Scholar 

  2. Papotti M, Ghe C, Cassoni P et al (2000) Growth hormone secretagogue binding sites in peripheral human tissues. J Clin Endocrinol Metab 85:3803–3807. doi:10.1210/jc.85.10.3803

    Article  CAS  PubMed  Google Scholar 

  3. Volante M, Allia E, Gugliotta P et al (2002) Expression of ghrelin and GHS receptor by pancreatic islet cells and related endocrine tumours. J Clin Endocrinol Metab 87:1300–1308. doi:10.1210/jc.87.3.1300

    Article  CAS  PubMed  Google Scholar 

  4. Broglio F, Prodam F, Me E et al (2005) Ghrelin: endocrine, metabolic and cardiovascular actions. J Endocrinol Invest 28:23–25

    CAS  PubMed  Google Scholar 

  5. Schmid DA, Held K, Ising M et al (2005) Ghrelin stimulates appetite, imagination of food, GH, ACTH, and cortisol, but does not affect leptin in normal controls. Neuropsychopharmacology 30:1187–1192. doi:10.1038/sj.npp.1300670

    Article  CAS  PubMed  Google Scholar 

  6. Allison KC, Ahima RS, O’Reardon JP et al (2005) Neuroendocrine profiles associated with energy intake, sleep, and stress in the night eating syndrome. J Clin Endocrinol Metab 90:6214–6217. doi:10.1210/jc.2005-1018

    Article  CAS  PubMed  Google Scholar 

  7. Cummings DE, Purnell JQ, Frayo RS et al (2001) A preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans. Diabetes 50:1714–1719. doi:10.2337/diabetes.50.8.1714

    Article  CAS  PubMed  Google Scholar 

  8. Heath RB, Jones R, Frayn KN et al (2004) Vagal stimulation exaggerates the inhibitory ghrelin response to oral fat in humans. J Endocrinol 180:273–281. doi:10.1677/joe.0.1800273

    Article  CAS  PubMed  Google Scholar 

  9. Beck B, Richy S, Stricker-Krongrad A (2003) Ghrelin and body weight regulation in the obese Zucker rat in relation to feeding state and dark/light cycle. Exp Biol Med (Maywood) 228:1124–1131

    CAS  Google Scholar 

  10. Tang-Christensen M, Vrang N, Ortmann S et al (2004) Central administration of ghrelin and agouti-related protein (83–132) increases food intake and decreases spontaneous locomotor activity in rats. Endocrinology 145:4645–4652. doi:10.1210/en.2004-0529

    Article  CAS  PubMed  Google Scholar 

  11. Wren AM, Seal LJ, Cohen MA et al (2001) Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 86:5992. doi:10.1210/jc.86.12.5992

    Article  CAS  PubMed  Google Scholar 

  12. Wren AM, Small CJ, Abbott CR et al (2001) Ghrelin causes hyperphagia and obesity in rats. Diabetes 50:2540–2547. doi:10.2337/diabetes.50.11.2540

    Article  CAS  PubMed  Google Scholar 

  13. Wang G, Lee HM, Englander E et al (2002) Ghrelin: not just another stomach hormone. Regul Pept 105:75–81. doi:10.1016/S0167-0115(02)00012-5

    Article  CAS  PubMed  Google Scholar 

  14. Levin F, Edholm T, Ehrstrom M et al (2005) Effect of peripherally administered ghrelin on gastric emptying and acid secretion in the rat. Regul Pept 131:59–65. doi:10.1016/j.regpep.2005.06.001

    Article  CAS  PubMed  Google Scholar 

  15. Lee HM, Wang G, Englander EW et al (2002) Ghrelin, a new gastrointestinal endocrine peptide that stimulates insulin secretion: enteric distribution, ontogeny, influence of endocrine, and dietary manipulations. Endocrinology 143:185–190. doi:10.1210/en.143.1.185

    Article  CAS  PubMed  Google Scholar 

  16. Arosio M, Ronchi CL, Gebbia C et al (2003) Stimulatory effects of ghrelin on circulating somatostatin and pancreatic polypeptide levels. J Clin Endocrinol Metab 88:701–704. doi:10.1210/jc.2002-021161

    Article  CAS  PubMed  Google Scholar 

  17. Ukkola O, Ravussin E, Jacobson P et al (2001) Mutations in the preproghrelin/ghrelin gene associated with obesity in humans. J Clin Endocrinol Metab 86(8):3996–3999. doi:10.1210/jc.86.8.3996

    Article  CAS  PubMed  Google Scholar 

  18. Hinney A, Hoch A, Geller F et al (2002) Ghrelin gene: identification of missense variants and a frameshift mutation in extremely obese children and adolescents and healthy normal weight students. J Clin Endocrinol Metab 87(6):2716–2719. doi:10.1210/jc.87.6.2716

    Article  CAS  PubMed  Google Scholar 

  19. Korbonits M, Gueorguiev M, O’Grady E et al (2002) A variation in the ghrelin gene increases weight and decreases insulin secretion in tall, obese children. J Clin Endocrinol Metab 87(8):4005–4008. doi:10.1210/jc.87.8.4005

    Article  CAS  PubMed  Google Scholar 

  20. Vivenza D, Rapa A, Castellino N et al (2004) Ghrelin gene polymorphisms and ghrelin, insulin, IGF-I, leptin and anthropometric data in children and adolescents. Eur J Endocrinol 151(1):127–133. doi:10.1530/eje.0.1510127

    Article  CAS  PubMed  Google Scholar 

  21. Vartiainen J, Kesaniemi YA, Ukkola O (2006) Sequencing analysis of ghrelin gene 5’ flanking region: relations between the sequence variants, fasting plasma total ghrelin concentrations, and body mass index. Metabolism 55(10):1420–1425. doi:10.1016/j.metabol.2006.06.014

    Article  CAS  PubMed  Google Scholar 

  22. Kuzuya M, Ando F, Iguchi A et al (2006) Preproghrelin Leu72Met variant contributes to overweight in middle-aged men of a Japanese large cohort. Int J Obes Lond 30:1609–1614. doi:10.1038/sj.ijo.0803296

    Article  CAS  PubMed  Google Scholar 

  23. Group of China Obesity Task Force (2004) Body mass index reference norm for screening overweight and obesity in Chinese children and adolescents. Clin J Epidemiol 25(2):97–102

    Google Scholar 

  24. Matthews DR, Hosker JP, Rudenski AS et al (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419. doi:10.1007/BF00280883

    Article  CAS  PubMed  Google Scholar 

  25. WHO (1999) Definition, diagnosis and classification of diabetes mellitus and its complications. Report of a WHO consultation. Part 1: diagnosis and classification of diabetes mellitus (WHO/NCD/NCS/99.2). World Health Organization, Geneva

    Google Scholar 

  26. Kim SY, Jo DS, Hwang PH et al (2006) Preproghrelin Leu72Met polymorphism is not associated with type 2 diabetes mellitus. Metabolism 55(3):366–370. doi:10.1016/j.metabol.2005.09.011

    Article  CAS  PubMed  Google Scholar 

  27. Shiiya T, Nakazato M, Mizuta M et al (2002) Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 87:240–244. doi:10.1210/jc.87.1.240

    Article  CAS  PubMed  Google Scholar 

  28. Haqq AM, Farooqi IS, O’Rahilly S et al (2003) Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome. J Clin Endocrinol Metab 88:174–178. doi:10.1210/jc.2002-021052

    Article  CAS  PubMed  Google Scholar 

  29. Tritos NA, Kokkinos A, Lampadariou E et al (2003) Cerebrospinal fluid ghrelin is negatively associated with body mass index. J Clin Endocrinol Metab 88:2943–2946. doi:10.1210/jc.2003-030300

    Article  CAS  PubMed  Google Scholar 

  30. Leidy HJ, Gardner JK, Frye BR et al (2004) Circulating ghrelin is sensitive to changes in body weight during a diet and exercise program in normal-weight young women. J Clin Endocrinol Metab 89:2659–2664. doi:10.1210/jc.2003-031471

    Article  CAS  PubMed  Google Scholar 

  31. Suematsu M, Katsuki A, Sumida Y et al (2005) Decreased circulating levels of active ghrelin are associated with increased oxidative stress in obese subjects. Eur J Endocrinol 153:403–407. doi:10.1530/eje.1.01977

    Article  CAS  PubMed  Google Scholar 

  32. McLaughlin T, Abbasi F, Lamendola C et al (2004) Plasma ghrelin concentrations are decreased in insulin-resistant obese adults relative to equally obese insulin-sensitive controls. J Clin Endocrinol Metab 89:1630–1635. doi:10.1210/jc.2003-031572

    Article  CAS  PubMed  Google Scholar 

  33. Broglio F, Gianotti L, Destefanis S et al (2004) The endocrine response to acute ghrelin administration is blunted in patients with anorexia nervosa, a ghrelin hypersecretory state. Clin Endocrinol (Oxf) 60:592–599. doi:10.1111/j.1365-2265.2004.02011.x

    Article  CAS  Google Scholar 

  34. Misra M, Miller KK, Stewart V et al (2005) Ghrelin and bone metabolism in adolescent girls with anorexia nervosa and healthy adolescents. J Clin Endocrinol Metab 90:5082–5087. doi:10.1210/jc.2005-0512

    Article  CAS  PubMed  Google Scholar 

  35. Nagaya N, Itoh T, Murakami S et al (2005) Treatment of cachexia with ghrelin in patients with COPD. Chest 128:1187–1193. doi:10.1378/chest.128.3.1187

    Article  CAS  PubMed  Google Scholar 

  36. Soriano-Guillen L, Barrios V, Martos G et al (2004) Effect of oral glucose administration on ghrelin levels in obese children. Eur J Endocrinol 151:119–121. doi:10.1530/eje.0.1510119

    Article  CAS  PubMed  Google Scholar 

  37. Wortley KE, Anderson KD, Garcia K et al (2004) Genetic deletion of ghrelin does not decrease food intake but influences metabolic fuel preference. Proc Natl Acad Sci USA 101:8227–8232. doi:10.1073/pnas.0402763101

    Article  CAS  PubMed  Google Scholar 

  38. Sun Y, Ahmed S, Smith RG (2003) Deletion of ghrelin impairs neither growth nor appetite. Mol Cell Biol 23:7973–7981. doi:10.1128/MCB.23.22.7973-7981.2003

    Article  CAS  PubMed  Google Scholar 

  39. Flanagan DE, Evans ML, Monsod TP et al (2003) The influence of insulin on circulating ghrelin. Am J Physiol Endocrinol Metab 284:E313–E316

    CAS  PubMed  Google Scholar 

  40. Mohlig M, Spranger J, Otto B et al (2002) Euglycemic hyperinsulinemia, but not lipid infusion, decreases circulating ghrelin levels in humans. J Endocrinol Invest 25:RC36–RC38

    CAS  PubMed  Google Scholar 

  41. Spranger J, Ristow M, Otto B et al (2003) Post-prandial decrease of human plasma ghrelin in the absence of insulin. J Endocrinol Invest 26:RC19–RC22

    CAS  PubMed  Google Scholar 

  42. Schaller G, Schmidt A, Pleiner J et al (2003) Plasma ghrelin concentrations are not regulated by glucose or insulin: a double-blind, placebo-controlled crossover clamp study. Diabetes 52:16–20. doi:10.2337/diabetes.52.1.16

    Article  CAS  PubMed  Google Scholar 

  43. Bing C, Ambye L, Fenger M et al (2005) Large-scale studies of the Leu72Met polymorphism of the ghrelin gene in relation to the metabolic syndrome and associated quantitative traits. Diabet Med 22(9):1157–1160. doi:10.1111/j.1464-5491.2005.01575.x

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We thank all children and their parents for participating in this research project. We also thank Chun Ling Wang, Fang Hong, Guan Ping Dong and Ke Huang for their exceptional patient care and organization. This project is supported by Zhejiang Provincial Technology Committee (2008C03002-1) and Zhejiang Education Committee (20050969).

Author information

Authors and Affiliations

  1. Department of Endocrinology, The Children’s Hospital of Zhejiang University School of Medicine, 57 Zhugan Xiang, Hangzhou, 310003, China

    J. F. Zhu, L. Liang, C. C. Zou & J. F. Fu

Authors
  1. J. F. Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. Liang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. C. Zou
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. F. Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to L. Liang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zhu, J.F., Liang, L., Zou, C.C. et al. Plasma ghrelin levels and polymorphisms of ghrelin gene in Chinese obese children and adolescents. Ir J Med Sci 179, 345–349 (2010). https://doi.org/10.1007/s11845-010-0494-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11845-010-0494-2

Keywords

Search

Navigation