Obesity Surgery

, Volume 19, Issue 1, pp 29–35 | Cite as

Ghrelin and Obestatin Levels in Severely Obese Women Before and After Weight Loss After Roux-en-Y Gastric Bypass Surgery

  • Christian L. RothEmail author
  • Thomas Reinehr
  • Gerit-Holger Schernthaner
  • Hans-Peter Kopp
  • Stefan Kriwanek
  • Guntram Schernthaner
Research Article



Ghrelin and obestatin are derived from the same gene but have different effects: Ghrelin stimulates appetite, and previous—albeit inconsistent—data show that obestatin may be involved in satiety. The present study was designed to test the hypothesis that Roux-en-Y gastric bypass (RYGB) surgery and/or the weight loss that reliably results from this procedure would alter levels of ghrelin and obestatin and ghrelin/obestatin ratios in a cohort of morbidly obese women.


This is a longitudinal follow-up study in 18 morbidly obese women (mean weight 131.2 kg, mean body mass index [BMI] 47.4). Clinical parameters and fasting serum concentrations of ghrelin, obestatin, triglycerides, low-density lipoprotein cholesterol, glucose, and insulin were measured before and 2 years after RYGB surgery, which was associated with body weight reductions of 41.5 ± 11.6 kg (mean 62.5% excess weight loss).


Ghrelin concentrations (−12%, p = 0.022) and ghrelin/obestatin ratios (−14%, p = 0.017) were lower after surgery than before, while obestatin levels did not change. Changes in ghrelin concentrations correlated with changes in insulin levels (r = 0.45, p = 0.011). Most cardiovascular risk factors studied improved postsurgically (p < 0.01).


In contrast to previous weight loss studies involving gastric banding, ghrelin levels decreased and obestatin levels remained stable after massive weight loss in long-term follow-up. The favorable gastrointestinal hormone profiles observed are likely to contribute to the long-term weight loss success rate attributed to RYGB.


Ghrelin Obestatin Gastric bypass Cardiovascular risk factors Obesity Weight loss Roux-en Y gastric bypass 



We thank Ms. R. Maslak and Ms. K. Schark-Zimmer, Children’s Hospital University of Bonn, for their support in the laboratory and Ms. M. Neff-Heinrich for her kind help in editing the paper.

This work has been supported by the Bonfor Research Foundation, University of Bonn, Germany and by NIH RR0163 and DK 62202 and by Scientific Grants from the Austrian Diabetes Association and from Eli Lilly Austria.


  1. 1.
    Foster-Schubert KE, Cummings DE. Emerging therapeutic strategies for obesity. Endocr Rev. 2006;27:779–93.CrossRefGoogle Scholar
  2. 2.
    Cummings DE, Overduin J, Foster-Schubert KE. Gastric bypass for obesity: mechanisms of weight loss and diabetes resolution. J Clin Endocrinol Metab. 2004;89:2608–15.CrossRefGoogle Scholar
  3. 3.
    Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, et al. The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology. 2000;141:4325–8.CrossRefGoogle Scholar
  4. 4.
    Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, et al. A role for ghrelin in the central regulation of feeding. Nature. 2001;409:194–8.CrossRefGoogle Scholar
  5. 5.
    Ahima RS. Ghrelin—a new player in glucose homeostatis? Cell Metab. 2006;3:301–2.CrossRefGoogle Scholar
  6. 6.
    Ikezaki A, Hosoda H, Ito K, Iwama S, Miura N, Matsuoka H, et al. Fasting plasma ghrelin levels are negatively correlated with insulin resistance and PAI-1, but not with leptin in obese children and adolescents. Diabetes. 2002;51:3408–11.CrossRefGoogle Scholar
  7. 7.
    Bellone S, Castellino N, Broglio F, Rapa A, Vivenza D, Radetti G, et al. Ghrelin secretion in childhood is refractory to the inhibiting effect of feeding. J Clin Endocrinol Metab. 2004;89:1662–5.CrossRefGoogle Scholar
  8. 8.
    Choi KM, Lee J, Lee KW, Seo JA, Oh JH, Kim SG, et al. The association between plasma adiponectin, ghrelin levels, and cardiovascular risk factors. Eur J Endocrinol. 2004;150:715–8.CrossRefGoogle Scholar
  9. 9.
    Cummings DE. Ghrelin and the short- and long-term regulation of appetite and body weight. Physiol Behav. 2006;89:71–84.CrossRefGoogle Scholar
  10. 10.
    Zhang JV, Ren PG, Avsian-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;310:996–9.CrossRefGoogle Scholar
  11. 11.
    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.CrossRefGoogle Scholar
  12. 12.
    Tremblay F, Perreault M, Klaman LD, Tobin JF, Smith E, Gimeno RE. Normal food intake and body weight in mice lacking the G protein-coupled receptor GPR39. Endocrinology. 2007;148:501–6.CrossRefGoogle Scholar
  13. 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;148:21–6.CrossRefGoogle Scholar
  14. 14.
    Tschöp M, Weyer C, Tataranni A, Devanarayan V, Ravussin E, Heiman ML. Circulating ghrelin levels are decreased in human obesity. Diabetes. 2001;50:707–9.CrossRefGoogle Scholar
  15. 15.
    Soriano-Guillen L, Barrios V, Campos-Barros A, Argente J. Ghrelin levels in obesity and anorexia nervosa: effect of weight reduction or recuperation. J Pediatr. 2004;144:36–42.CrossRefGoogle Scholar
  16. 16.
    Reinehr T, Roth CL, Alexy U, Kersting M, Kiess W, Andler W. Ghrelin levels before and after reduction of overweight due to a low fat high carbohydrate diet in obese children and adolescents. Int J Obes. 2005;29:362–8.CrossRefGoogle Scholar
  17. 17.
    De Ambrogi M, Volpe S, Tamanini C. Ghrelin central and peripheral effects of a novel peptydil hormon. Med Sci Monit. 2003;9:217–24.Google Scholar
  18. 18.
    Cummings DE, Weigle DS, Frayo RS, Breen PA, Ma MK, Dellinger EP, et al. Plasma ghrelin levels after diet-induced weight loss or gastric bypass surgery. N Engl J Med. 2002;346:1623–30.CrossRefGoogle Scholar
  19. 19.
    Garcia JM, Iyer D, Posten WCS, Marcelli M, Reeves R, Foreyt J, et al. Rise of plasma ghrelin with weight loss is not sustained during weight maintenance. Obesity. 2006;14:1716–23.CrossRefGoogle Scholar
  20. 20.
    Weigle DS, Cummings DE, Newby PD, Breen PA, Frayo RS, Matthys CC, et al. Roles of leptin and ghrelin in the loss of body weight caused by a low fat, high carbohydrate diet. J Clin Endocrinol Metab. 2003;88:1577–86.CrossRefGoogle Scholar
  21. 21.
    Haider DG, Schindler K, Prager G, Bohdjalian A, Luger A, Wolzt M, et al. Serum retinol-binding protein-4 is reduced after weight loss in morbidly obese subjects. J Clin Endocrinol Metab. 2007;92:1111–68.CrossRefGoogle Scholar
  22. 22.
    Frühbeck G, Diez-Caballero A, Gil MJ, Montero I, Gómez-Ambrosi J, Salvador J, et al. The decrease in plasma ghrelin concentrations following bariatric surgery depends on the functional integrity of the fundus. Obes Surg. 2004;14:606–12.CrossRefGoogle Scholar
  23. 23.
    Faraj M, Havel PJ, Phélis S, Blank D, Sniderman AD, Cianflone K. Plasma acylation-stimulating protein, adiponectin, leptin, and ghrelin before and after weight loss induced by gastric bypass surgery in morbidly obese subjects. J Clin Endocrinol Metab. 2003;88:1594–602.CrossRefGoogle Scholar
  24. 24.
    Shah M, Simha V, Garg A. Long-term impact of bariactric surgery on body weight, comorbidities, and nutritional Status. J Clin Endocrinol Metab. 2006;91:4223–31.CrossRefGoogle Scholar
  25. 25.
    Must A, Spadano J, Coakley EH, Field AE, Colditz G, Dietz WH. The disease burden associated with overweight and obesity. JAMA. 1999;282:1523–9.CrossRefGoogle Scholar
  26. 26.
    Reinehr T, Roth CL, Schernthaner GH, Kopp HP, Kriwanek S, Schernthaner G. Peptide YY and glucagon-like peptide-1 in morbidly obese patients before and after surgically induced weight loss. Obes Surg. 2007;17:1571–7.CrossRefGoogle Scholar
  27. 27.
    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;28:412–9.CrossRefGoogle Scholar
  28. 28.
    Williams D, Grill HJ, Cummings DE, Kaplan JM. Vagotomy dissociates short- and long-term controls of circulating ghrelin. Endocrinology. 2003;144:5184–7.CrossRefGoogle Scholar
  29. 29.
    Frühbeck G, Diez Caballero A, Gil MJ. Fundus functionality and ghrelin concentrations after bariatric surgery. N Engl J Med. 2004;350:308–9.CrossRefGoogle Scholar
  30. 30.
    Cowley MA, Smith RG, Diano S, Tschop M, Pronchuk N, Grove KL, et al. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron. 2003;37:649–61.CrossRefGoogle Scholar
  31. 31.
    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;46:426–34.CrossRefGoogle Scholar
  32. 32.
    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;351:21–5.CrossRefGoogle Scholar
  33. 33.
    Noueiras R, Tschöp M. Biomedicine. Separation of conjoined hormones yields appetite rivals. Science. 2005;310:985–6.CrossRefGoogle Scholar
  34. 34.
    Chartrel N, Alvear-Perez R, Leprince J, Iturrioz X, Reaux-Le Goazigo A, Audinot V, et al. Comment on “Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin’s effects on food intake”. Science. 2007;315:766–7.CrossRefGoogle Scholar
  35. 35.
    Reinehr T, de Sousa G, Roth CL. Obestatin and ghrelin levels in obese children and adolescents before and after reduction of overweight. Clin Endocrinol. 2008;68:304–10.Google Scholar
  36. 36.
    Guo ZF, Zheng X, Qin YW, Hu JQ, Chen SP, Zhang Z. Circulating preprandial ghrelin to obestatin ratio is increased in human obesity. J Clin Endocrinol Metab. 2007;92:1875–80.CrossRefGoogle Scholar
  37. 37.
    le Roux CW, Aylwin SJ, Batterham RL, Borg CM, Coyle F, Prasad V, et al. Gut hormone profiles following bariatric surgery favor an anorectic state, facilitate weight loss, and improve metabolic parameters. Ann Surg. 2006;243:108–14.CrossRefGoogle Scholar
  38. 38.
    Purnell JQ, Weigle DS, Breen P, Cummings DE. Ghrelin levels correlate with insulin levels, insulin resistance, and high-density lipoprotein cholesterol, but not with gender, menopausal status, or cortisol levels in humans. J Clin Endocrinol Metab. 2003;88:5747–52.CrossRefGoogle Scholar
  39. 39.
    Qi X, Li L, Yang G, Liu J, Li K, Tang Y, et al. Circulating obestatin levels in normal subjects and in patients with impaired glucose regulation and type 2 diabetes mellitus. Clin Endocrinol (Oxf). 2007;66:593–7.Google Scholar
  40. 40.
    Akamizu T, Shinomiya T, Irako T, Fukunaga M, Nakai Y, Nakai Y, et al. Separate measurement of plasma levels of acylated and desacyl ghrelin in healthy subjects using a new direct ELISA assay. J Clin Endocrinol Metab. 2005;90:6–9.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2008

Authors and Affiliations

  • Christian L. Roth
    • 1
    Email author
  • Thomas Reinehr
    • 2
  • Gerit-Holger Schernthaner
    • 3
  • Hans-Peter Kopp
    • 4
  • Stefan Kriwanek
    • 5
  • Guntram Schernthaner
    • 4
  1. 1.Seattle Children’s Hospital Research InstituteSeattleUSA
  2. 2.Vestische Hospital for Children and Adolescents DattelnUniversity of Witten/HerdeckeWittenGermany
  3. 3.Department of Medicine II, Division of AngiologyMedical University of ViennaViennaAustria
  4. 4.Department of Medicine IRudolfstiftung Hospital ViennaViennaAustria
  5. 5.Department of SurgeryRudolfstiftung Hospital ViennaViennaAustria

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