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:

Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal

Abstract

Objective:

To investigate a potential role for obestatin in humans by examining response to a fixed energy meal.

Context:

A new anorectic peptide hormone, obestatin has recently been isolated from rat stomach. The significance of this peptide in humans is unknown.

Study design:

Case-control study.

Setting:

Hospital-based study.

Patients:

Nine healthy controls, nine morbidly obese subjects and eight post-gastrectomy subjects.

Intervention:

Subjects attended after an overnight fast and were given a fixed energy meal (1550 kJ).

Main outcome measure:

The response of obestatin to a meal in the different groups.

Results:

Fasting obestatin was significantly lower in obese subjects as compared to lean subjects (27.8±4 vs 17.2±2 pg/ml, P=0.03). Obestatin was also decreased in gastrectomy subjects but this did not reach statistical significance (27.8±4 vs 21.9±3 pg/ml, P=0.3). Obestatin did not change significantly from baseline in response to the meal. Lean and obese subjects had a similar obestatin/ghrelin ratio (0.04±0.003 vs 0.05±0.009, P=0.32), but this was higher in the gastrectomy group (0.04±0.003 vs 0.1±0.01, P<0.001).

Conclusions:

Obestatin does not vary significantly with a fixed energy meal, but is significantly lower in morbidly obese subjects as compared to lean subjects supporting a possible role for obestatin in long-term body weight regulation. Obestatin tended to be lower in gastrectomy subjects and their obestatin/ghrelin ratio differed from healthy controls. Hence, the expression of obestatin is altered following gastrectomy, suggesting other sites outside the stomach may also secrete obestatin.

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
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K . Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999; 402: 656–660.

    Article  CAS  Google Scholar 

  2. Wren AM, Seal LJ, Cohen MA, Brynes AE, Frost GS, Murphy KG et al. Ghrelin enhances appetite and increases food intake in humans. J Clin Endocrinol Metab 2001; 86: 5992.

    Article  CAS  Google Scholar 

  3. Wren AM, Small CJ, Abbott CR, Dhillo WS, Seal LJ, Cohen MA et al. Ghrelin causes hyperphagia and obesity in rats. Diabetes 2001; 50: 2540–2547.

    Article  CAS  Google Scholar 

  4. Zhang JV, Ren PG, vsian-Kretchmer O, Luo CW, Rauch R, Klein C et al. Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake. Science 2005; 310: 996–999.

    Article  CAS  PubMed  Google Scholar 

  5. McKee KK, Tan CP, Palyha OC, Liu J, Feighner SD, Hreniuk DL et al. Cloning and characterization of two human G protein-coupled receptor genes (GPR38 and GPR39) related to the growth hormone secretagogue and neurotensin receptors. Genomics 1997; 46: 426–434.

    Article  CAS  PubMed  Google Scholar 

  6. Jackson VR, Nothacker HP, Civelli O . GPR39 receptor expression in the mouse brain. Neuroreport 2006; 17: 813–816.

    Article  CAS  PubMed  Google Scholar 

  7. Holst B, Egerod KL, Schild E, Vickers SP, Cheetham S, Gerlach LO et al. GPR39 signaling is stimulated by zinc ions but not by obestatin. Endocrinology 2007; 148: 13–20.

    Article  CAS  PubMed  Google Scholar 

  8. Lauwers E, Landuyt B, Arckens L, Schoofs L, Luyten W . Obestatin does not activate orphan G protein-coupled receptor GPR39. Biochem Biophys Res Commun 2006; 351: 21–25.

    Article  CAS  PubMed  Google Scholar 

  9. Szentirmai E, Hajdu I, Obal Jr F, Krueger JM . Ghrelin-induced sleep responses in ad libitum fed and food-restricted rats. Brain Res 2006; 1088: 131–140.

    Article  CAS  PubMed  Google Scholar 

  10. Szentirmai E, Krueger JM . Obestatin alters sleep in rats. Neurosci Lett 2006; 404: 222–226.

    Article  CAS  PubMed  Google Scholar 

  11. Bresciani E, Rapetti D, Dona F, Bulgarelli I, Tamiazzo L, Locatelli V et al. Obestatin inhibits feeding but does not modulate GH and corticosterone secretion in the rat. J Endocrinol Invest 2006; 29: RC16–RC18.

    Article  CAS  PubMed  Google Scholar 

  12. Moechars D, Depoortere I, Moreaux B, de SB, Goris I, Hoskens L et al. Altered gastrointestinal and metabolic function in the GPR39-obestatin receptor-knockout mouse. Gastroenterology 2006; 131: 1131–1141.

    Article  CAS  PubMed  Google Scholar 

  13. Nogueiras R, Pfluger P, Tovar S, Myrtha A, Mitchell S, Morris A et al. Effects of obestatin on energy balance and growth hormone secretion in rodents. Endocrinology 2007; 148: 21–26.

    Article  CAS  PubMed  Google Scholar 

  14. Seoane LM, Al-Massadi O, Pazos Y, Pagotto U, Casanueva FF . Central obestatin administration does not modify either spontaneous or ghrelin-induced food intake in rats. J Endocrinol Invest 2006; 29: RC13–RC15.

    Article  CAS  PubMed  Google Scholar 

  15. Park WH, Oh YJ, Kim GY, Kim SE, Paik KH, Han SJ et al. Obestatin is not elevated or correlated with insulin in children with Prader–Willi syndrome. J Clin Endocrinol Metab 2007; 92: 229–234.

    Article  CAS  PubMed  Google Scholar 

  16. Tschop M, Weyer C, Tataranni PA, Devanarayan V, Ravussin E, Heiman ML . Circulating ghrelin levels are decreased in human obesity. Diabetes 2001; 50: 707–709.

    Article  CAS  Google Scholar 

  17. Jeon TY, Lee S, Kim HH, Kim YJ, Son HC, Kim DH et al. Changes in plasma ghrelin concentration immediately after gastrectomy in patients with early gastric cancer. J Clin Endocrinol Metab 2004; 89: 5392–5396.

    Article  CAS  Google Scholar 

  18. Cummings DE, Frayo RS, Marmonier C, Aubert R, Chapelot D . Plasma ghrelin levels and hunger scores in humans initiating meals voluntarily without time- and food-related cues. Am J Physiol Endocrinol Metab 2004; 287: E297–E304.

    Article  CAS  Google Scholar 

  19. English PJ, Ghatei MA, Malik IA, Bloom SR, Wilding JP . Food fails to suppress ghrelin levels in obese humans. J Clin Endocrinol Metab 2002; 87: 2984.

    Article  CAS  Google Scholar 

  20. Catalan V, Gomez-Ambrosi J, Rotellar F, Silva C, Gil MJ, Rodriguez A et al. The obestatin receptor (GPR39) is expressed in human adipose tissue and is down-regulated in obesity-associated type 2 diabetes mellitus. Clin Endocrinol (Oxf) 2007; 66: 598–601.

    CAS  Google Scholar 

  21. Ariyasu H, Takaya K, Tagami T, Ogawa Y, Hosoda K, Akamizu T et al. Stomach is a major source of circulating ghrelin, and feeding state determines plasma ghrelin-like immunoreactivity levels in humans. J Clin Endocrinol Metab 2001; 86: 4753–4758.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

We thank Jackie Cleator, Barbara Martin and Janet Cashen for all of their hard work on the study, as well as all of the volunteers who took part. We also thank Norman Usher, Carole Thomas and Andrew Birss for their help with laboratory work, and Rhian Jones for her help with recruitment. Lastly, we thank Pharmacia for sponsorship. This work was supported by an International Endocrine Research Prize from Pharmacia awarded to JP.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to J P H Wilding.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Huda, M., Durham, B., Wong, S. et al. Plasma obestatin levels are lower in obese and post-gastrectomy subjects, but do not change in response to a meal. Int J Obes 32, 129–135 (2008). https://doi.org/10.1038/sj.ijo.0803694

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0803694

Keywords

This article is cited by

Search

Quick links