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Changes in serum ghrelin predict weight loss after Roux-en-Y gastric bypass in rats

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Abstract

Background

Although Roux-en-Y gastric bypass (RYGB) is an effective and widely used therapy for severe obesity, the mechanisms by which it induces weight loss are not well understood. Several studies have shown that RYGB in human patients causes a decrease in circulating levels of ghrelin, a gastric hormone that strongly stimulates food intake. Substantial variation in the effect of RYGB on serum ghrelin has been reported in different studies and among individual patients, suggesting that regulation of this hormone is complex and subject to genetic and other patient-specific factors. To control for these factors and to enable more detailed study of physiologic mechanisms, we have recently developed a clinically relevant rat model of RYGB. In this study, we used this model to examine the effect of RYGB on serum ghrelin levels.

Methods

Fifteen Sprague-Dawley rats that had received a high-fat diet to induce moderate obesity underwent RYGB. The operation closely resembled the procedure in humans. Serum samples were collected 1 month before and 3 months after RYGB, and serum ghrelin levels were measured. The primary outcomes of the study were the changes in body weight, food intake, and circulating ghrelin levels after RYGB. A multiple linear regression model was developed to examine the relationship between ghrelin levels and weight change after RYGB.

Results

Three months after the procedure, RYGB-treated rats weighed 20 ± 5% less than they would have, had they not undergone the procedure. Despite the weight loss, serum ghrelin levels were 38 ± 6% lower than before surgery. There was appreciable variation in the weight loss in individual animals, and preoperative weight and pre- and postoperative ghrelin levels were the best predictors of postoperative weight loss. Thus, the animals who had the greatest weight loss were those that were heaviest before surgery. These rats had the highest preoperative and lowest postoperative ghrelin levels.

Conclusions

Using our recently developed rat model of RYGB, we found that postoperative weight loss is correlated with the magnitude of the decrease in circulating ghrelin levels. This correlation provides the strongest evidence to date that altered ghrelin signaling contributes to weight loss after this operation. The lower level of circulating ghrelin after RYGB likely blunts the appetitive drive, leading to decreased food intake in these animals.

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References

  1. A Asakawa A Inui T Kaga H Yuzuriha T Nagata N Ueno S Makino et al. (2001) ArticleTitleGhrelin is an appetite-stimulatory signal from stomach with structural resemblance to motilin Gastroenterology 120 637–345 Occurrence Handle10.1053/gast.2001.22158

    Article  Google Scholar 

  2. CW Baker LM Kaplan (2003) ArticleTitleThe impact of gastric surgery on hunger, satiety and non-hunger–related desire to eat Obes Res 11 A109–A110

    Google Scholar 

  3. BM Balsiger FP Kennedy HS Abu-Lebdeh M Collazo-Clavell MD Jensen T O’Brien DD Hensrud et al. (2000) ArticleTitleProspective evaluation of Roux-en-Y gastric bypass as primary operation for medically complicated obesity Mayo Clin Proc 75 673–680 Occurrence Handle10907381

    PubMed  Google Scholar 

  4. RE Brolin (2002) ArticleTitleBariatric surgery and long-term control of morbid obesity JAMA 288 2793–2796 Occurrence Handle10.1001/jama.288.22.2793 Occurrence Handle12472304

    Article  PubMed  Google Scholar 

  5. PM Copeland P Davis LM Kaplan (2003) ArticleTitleWeight loss after gastric bypass is associated with decreased plasma gastric inhibitory polypeptide without a significant change in circulating ghrelin Obes Res 11 A17–A18

    Google Scholar 

  6. DE Cummings JQ Purnell RS Frayo K Schmidova BE Wisse DS Weigle (2001) ArticleTitleA preprandial rise in plasma ghrelin levels suggests a role in meal initiation in humans Diabetes 50 1714–1719 Occurrence Handle11473029

    PubMed  Google Scholar 

  7. DE Cummings DS Weigle RS Frayo PA Breen MK Ma EP Dellinger JQ Purnell (2002) ArticleTitleHuman plasma ghrelin levels after diet-induced weight loss and gastric bypass surgery N Engl J Med 346 1623–1630 Occurrence Handle10.1056/NEJMoa012908 Occurrence Handle12023994

    Article  PubMed  Google Scholar 

  8. M Faraj PJ Havel S Phelis D Blank AD Sniderman K Cianflone (2003) ArticleTitlePlasma 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 88 1594–1602 Occurrence Handle10.1210/jc.2002-021309 Occurrence Handle12679444

    Article  PubMed  Google Scholar 

  9. BL Fisher P Schauer (2002) ArticleTitleMedical and surgical options in the treatment of severe obesity Am J Surg 184 9S–16S Occurrence Handle10.1016/S0002-9610(02)01173-X Occurrence Handle12527344

    Article  PubMed  Google Scholar 

  10. L Flancbaum PS Choban LR Bradley JC Burge (1997) ArticleTitleChanges in measured resting energy expenditure after Roux-en-Y gastric bypass for clinically severe obesity Surgery 122 943–949 Occurrence Handle10.1016/S0039-6060(97)90336-6 Occurrence Handle9369895

    Article  PubMed  Google Scholar 

  11. U Hanusch-Enserer G Brabant M Roden (2003) ArticleTitleGhrelin concentrations in morbidly obese patients after adjustable gastric banding N Engl J Med 348 2159–2160 Occurrence Handle10.1056/NEJM200305223482125

    Article  Google Scholar 

  12. C Holdstock BE Engstrom M Ohrvall L Lind M Sundborn FA Karlsson (2003) ArticleTitleGhrelin and adipose tissue regulatory peptides: effect of gastric bypass surgery in obese humans J Clin Endocrinol Metab 88 3177–3183 Occurrence Handle10.1210/jc.2002-021734 Occurrence Handle12843162

    Article  PubMed  Google Scholar 

  13. M Kojima H Hosoda Y Date M Nakazato H Matsuo K Kangawa (1999) ArticleTitleGhrelin is a growth hormone–releasing acylated peptide from stomach Nature 402 656–660 Occurrence Handle10.1038/45230 Occurrence Handle10604470

    Article  PubMed  Google Scholar 

  14. F Leonetti G Silecchia G Iacobellis MC Ribaudo A Zappaterreno C Tiberti CV Iannucci et al. (2003) ArticleTitleDifferent plasma ghrelin levels after laparoscopic gastric bypass and adjustable gastric banding in morbid obese subjects J Clin Endocrinol Metab 88 4227–4231 Occurrence Handle10.1210/jc.2003-030133 Occurrence Handle12970291

    Article  PubMed  Google Scholar 

  15. BE Levin RE Keesey (1998) ArticleTitleDefense of differing body weight set points in diet-induced obese and resistant rats Am J Physiol 274 R412–R419 Occurrence Handle9486299

    PubMed  Google Scholar 

  16. BE Levin AA Dunn-Meynell B Balkan RE Keesey (1997) ArticleTitleSelective breeding for diet-induced obesity and resistance in Sprague-Dawley rats Am J Physiol 273 R725–R730 Occurrence Handle9277561

    PubMed  Google Scholar 

  17. M Nakazato N Murakami Y Date M Kojima H Matsuo K Kangawa S Matsukura (2001) ArticleTitleA role for ghrelin in the central regulation of feeding Nature 409 194–198 Occurrence Handle10.1038/35051587 Occurrence Handle11196643

    Article  PubMed  Google Scholar 

  18. WJ Pories MS Swanson KG MacDonald SB Long PG Morris BM Brown HA Barakat et al. (1995) ArticleTitleWho would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus Ann Surg 222 339–352 Occurrence Handle7677463

    PubMed  Google Scholar 

  19. PR Schauer S Ikramuddin W Gourash R Ramanathan J Luketich (2000) ArticleTitleOutcomes after laparoscopic Roux-en-Y gastric bypass for morbid obesity Ann Surg 232 515–529 Occurrence Handle10.1097/00000658-200010000-00007 Occurrence Handle10998650

    Article  PubMed  Google Scholar 

  20. N Stylopoulos J Pettit DW Rattner LM Kaplan (2003) ArticleTitleLong-term weight loss after gastric bypass surgery in rats is proportional to the degree of excess body weight Obes Res 11 A20

    Google Scholar 

  21. N Stylopoulos SM Maithel DB Jones DW Rattner LM Kaplan (2004) ArticleTitleIncreased energy expenditure accounts for a substantial-portion of the weight loss after Roux-en-Y gastric bypass in rats Gastroenterology 126 A90 Occurrence Handle10.1053/j.gastro.2003.10.014

    Article  Google Scholar 

  22. M Tschop ML Heiman (2001) ArticleTitleRodent obesity models: an overview Exp Clin Endocrinol Diabetes 109 307–319 Occurrence Handle10.1055/s-2001-17297 Occurrence Handle11571668

    Article  PubMed  Google Scholar 

  23. M Tschöp R Wawarta RL Riepl S Friedrich M Bidlingmaier R Landgraf C Folwaczny (2001) ArticleTitlePost-prandial decrease of circulating human ghrelin levels J Endocrinol Invest 24 RC19–RC21 Occurrence Handle11434675

    PubMed  Google Scholar 

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Acknowledgments

This work was supported by grants DK99010, DK43351, and DK46200 from the National Institutes of Health.

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Authors and Affiliations

  1. Massachusetts General Hospital Weight Center, Massachusetts General Hospital, 50 Staniford Street, Boston, MA 02114, USA

    N. Stylopoulos, P. Davis & L. M. Kaplan

  2. Department of Surgery, Massachusetts General Hospital, 50 Fruit Street, Boston, MA 02114, USA

    N. Stylopoulos & D. W. Rattner

  3. Gastrointestinal Unit and Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA

    P. Davis & L. M. Kaplan

  4. Department of Surgery, Harvard Medical School, 25 Shattuck Street, Boston, MA 02115, USA

    J. D. Pettit

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  1. N. Stylopoulos
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  2. P. Davis
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  3. J. D. Pettit
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  4. D. W. Rattner
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  5. L. M. Kaplan
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Correspondence to L. M. Kaplan.

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Stylopoulos, N., Davis, P., Pettit, J.D. et al. Changes in serum ghrelin predict weight loss after Roux-en-Y gastric bypass in rats. Surg Endosc 19, 942–946 (2005). https://doi.org/10.1007/s00464-004-8825-x

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  • DOI: https://doi.org/10.1007/s00464-004-8825-x

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