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:

Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial)

International Journal of Obesity volume 35, pages 829–837 (2011)Cite this article

Subjects

A Corrigendum to this article was published on 14 June 2011

Abstract

Background:

Entry of nutrients into the small intestine activates neuro-hormonal signals that regulate food intake through induction of satiation.

Objective:

To evaluate whether caloric intake can be decreased by pharmacologically accelerating gastric emptying (GE) of nutrients into the small intestine.

Methods:

Subjects were tested in 2 days, at baseline (day1) and after randomly receiving, in a double-blind manner, a 1 h infusion of erythromycin (3 mg Kg−1, to accelerate GE) or placebo (day 2). Ad libitum caloric intake and postprandial gastrointestinal symptoms were evaluated using a validated nutrient drink test, simultaneously measuring gastric by scintigraphy. Plasma levels of satiation factors were also measured to evaluate their role in the modification of caloric intake and postprandial symptoms. Acceleration of GE was assessed as the difference in percentage emptied between day 2 and day 1 (DGE). The effects of DGE on caloric intake and symptoms were evaluated using multiple (lineal) regression.

Results:

Among 30 overweight/obese subjects (24F and 6 M), 15 received erythromycin and 15 placebo. The overall median age was 36 years (IQR: 30–42) and body mass index was 30 Kg m−2 (IQR: 27–36). Subjects receiving erythromycin on day 2 presented accelerated GE as compared with placebo (P=0.0002). DGE at 15 min after initiating eating had a significant effect on prospective caloric intake (P=0.004). From the best-fitted regression model (R2=81%, P<0.0001), a 10% increase in GE at 15 min induced on an average a 135±43.5 Kcal decrease in caloric intake. Postprandial increase in cholecystokinin (CCK) (P=0.03) and insulin (P=0.02) was associated with decreased caloric intake. Acceleration of GE at 60 min after initiating eating increased postprandial symptom scores measured 30 min after the completion of food consumption (P=0.01). Postprandial increase in CCK (P=0.002) and PP (P=0.02) was associated with postprandial symptoms.

Conclusion:

Meal size can be reduced in overweight/obese subjects by pharmacologically accelerating GE. This may be a reasonable target in obesity management.

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

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

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

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. Kumanyika S, Jeffery RW, Morabia A, Ritenbaugh C, Antipatis VJ . Obesity prevention: the case for action. Int J Obes Relat Metab Disord 2002; 26: 425–436.

    Article  CAS  PubMed  Google Scholar 

  2. Woods SC . Gastrointestinal satiety signals I. An overview of gastrointestinal signals that influence food intake. Am J Physiol Gastrointest Liver Physiol 2004; 286: G7–G13.

    Article  CAS  PubMed  Google Scholar 

  3. Schwartz MW . Brain pathways controlling food intake and body weight. Exp Biol Med (Maywood) 2001; 226: 978–981.

    Article  CAS  Google Scholar 

  4. Delgado-Aros S, Camilleri M, Castillo EJ, Cremonini F, Stephens D, Ferber I et al. Effect of gastric volume or emptying on meal-related symptoms after liquid nutrients in obesity: a pharmacologic study. Clin Gastroenterol Hepatol 2005; 3: 997–1006.

    Article  CAS  PubMed  Google Scholar 

  5. Marmonier C, Chapelot D, Louis-Sylvestre J . Effects of macronutrient content and energy density of snacks consumed in a satiety state on the onset of the next meal. Appetite 2000; 34: 161–168.

    Article  CAS  PubMed  Google Scholar 

  6. Delgado-Aros S, Kim DY, Burton DD, Thomforde GM, Stephens D, Brinkmann BH et al. Effect of GLP-1 on gastric volume, emptying, maximum volume ingested, and postprandial symptoms in humans. Am J Physiol Gastrointest Liver Physiol 2002; 282: 424–431.

    Article  Google Scholar 

  7. Geliebter A, Hashim SA . Gastric capacity in normal, obese, and bulimic women. Physiol Behav 2001; 74: 743–746.

    Article  CAS  PubMed  Google Scholar 

  8. Delgado-Aros S, Cremonini F, Castillo JE, Chial HJ, Burton DD, Ferber I et al. Independent influences of body mass and gastric volumes on satiation in humans. Gastroenterology 2004; 126: 432–440.

    Article  PubMed  Google Scholar 

  9. Garner DM, Garfinkel PE . The Eating Attitudes Test: an index of the symptoms of anorexia nervosa. Psychol Med 1979; 9: 273–279.

    Article  CAS  PubMed  Google Scholar 

  10. Garner DM, Olmsted MP, Bohr Y, Garfinkel PE . The eating attitudes test: psychometric features and clinical correlates. Psychol Med 1982; 12: 871–878.

    Article  CAS  PubMed  Google Scholar 

  11. Mintz LB, O’Halloran MS . The Eating Attitudes Test: validation with DSM-IV eating disorder criteria. J Pers Assess 2000; 74: 489–503.

    Article  CAS  PubMed  Google Scholar 

  12. Geliebter A, Hassid G, Hashim SA . Test meal intake in obese binge eaters in relation to mood and gender. Int J Eat Disord 2001; 29: 488–494.

    Article  CAS  PubMed  Google Scholar 

  13. Geliebter A, Melton PM, McCray RS, Gallagher DR, Gage D, Hashim SA . Gastric capacity, gastric emptying, and test-meal intake in normal and bulimic women. Am J Clin Nutr 1992; 56: 656–661.

    Article  CAS  PubMed  Google Scholar 

  14. Zigmond AS, Snaith RP . The hospital anxiety and depression scale. Acta Psychiatr Scand 1983; 67: 361–370.

    Article  CAS  PubMed  Google Scholar 

  15. Johnston M, Pollard B, Hennessey P . Construct validation of the hospital anxiety and depression scale with clinical populations. J Psychosom Res 2000; 48: 579–584.

    Article  CAS  PubMed  Google Scholar 

  16. Delgado-Aros S, Chial HJ, Burton DD, McKinzie S, Ferber I, Camilleri C . Reliability of the nutrient drink test to assess maximum volume intake and postprandial symptoms. Gastroenterology 2002; 122 (4 Suppl 1): A-550.

    Google Scholar 

  17. Deutsch JA . The role of the stomach in eating. Am J Clin Nutr 1985; 42 (5 Suppl): 1040–1043.

    Article  CAS  PubMed  Google Scholar 

  18. Deutsch JA, Jang Ahn S . The splanchnic nerve and food intake regulation. Behav Neural Biol 1986; 45: 43–47.

    Article  CAS  PubMed  Google Scholar 

  19. Deutsch JA, Young WG, Kalogeris TJ . The stomach signals satiety. Science 1978; 201: 165–167.

    Article  CAS  PubMed  Google Scholar 

  20. Schwartz GJ, McHugh PR, Moran TH . Gastric loads and cholecystokinin synergistically stimulate rat gastric vagal afferents. Am J Physiol 1993; 265 (4 Part 2): 872–876.

    Google Scholar 

  21. Schwartz GJ, Moran TH, White WO, Ladenheim EE . Relationships between gastric motility and gastric vagal afferent responses to CCK and GRP in rats differ. Am J Physiol 1997; 272 (6 Part 2): 1726–1733.

    Google Scholar 

  22. Safieh-Garabedian B, Poole S, Allchorne A, Winter J, Woolf CJ . Contribution of interleukin-1 beta to the inflammation-induced increase in nerve growth factor levels and inflammatory hyperalgesia. British Journal of Pharmacology 1995; 115: 1265–1275.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Delgado-Aros S, Camilleri M, Cremonini F, Ferber I, Stephens D, Burton DD . Contributions of gastric volumes and gastric emptying to meal size and postmeal symptoms in functional dyspepsia. Gastroenterology 2004; 127: 1685–1694.

    Article  PubMed  Google Scholar 

  24. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL et al. Gut hormone PYY(3-36) physiologically inhibits food intake. Nature 2002; 418: 650–654.

    Article  CAS  PubMed  Google Scholar 

  25. Yuzuriha H, Inui A, Goto K, Asakawa A, Fujimiya M, Kasuga M . Intracerebroventricular administration of NPY stimulates resistin gene expression in mice. Int J Mol Med 2003; 11: 675–676.

    CAS  PubMed  Google Scholar 

  26. Smith GP, Jerome C, Norgren R . Afferent axons in abdominal vagus mediate satiety effect of cholecystokinin in rats. Am J Physiol 1985; 249 (5 Part 2): R638–R641.

    CAS  PubMed  Google Scholar 

  27. Wu XY, Zhu JX, Gao J, Owyang C, Li Y . Neurochemical phenotype of vagal afferent neurons activated to express C-FOS in response to luminal stimulation in the rat. Neuroscience 2005; 130: 757–767.

    Article  CAS  PubMed  Google Scholar 

  28. Reidelberger RD, Hernandez J, Fritzsch B, Hulce M . Abdominal vagal mediation of the satiety effects of CCK in rats. Am J Physiol Regul Integr Comp Physiol 2004; 286: R1005–R1012.

    Article  CAS  PubMed  Google Scholar 

  29. Koda S, Date Y, Murakami N, Shimbara T, Hanada T, Toshinai K et al. The role of the vagal nerve in peripheral PYY3-36-induced feeding reduction in rats. Endocrinology 2005; 146: 2369–2375.

    Article  CAS  PubMed  Google Scholar 

  30. Abbott CR, Monteiro M, Small CJ, Sajedi A, Smith KL, Parkinson JR et al. The inhibitory effects of peripheral administration of peptide YY(3-36) and glucagon-like peptide-1 on food intake are attenuated by ablation of the vagal-brainstem-hypothalamic pathway. Brain Res 2005; 1044: 127–131.

    Article  CAS  PubMed  Google Scholar 

  31. Gibbs J, Young RC, Smith GP . Cholecystokinin decreases food intake in rats. J Comp Physiol Psychol 1973; 84: 488–495.

    Article  CAS  PubMed  Google Scholar 

  32. West DB, Fey D, Woods SC . Cholecystokinin persistently suppresses meal size but not food intake in free-feeding rats. Am J Physiol 1984; 246 (5 Part 2): R776–R787.

    CAS  PubMed  Google Scholar 

  33. Schwartz GJ, McHugh PR, Moran TH . Pharmacological dissociation of responses to CCK and gastric loads in rat mechanosensitive vagal afferents. Am J Physiol 1994; 267 (1 Part 2): R303–R308.

    CAS  PubMed  Google Scholar 

  34. Baskin DG, Wilcox BJ, Figlewicz DP, Dorsa DM . Insulin and insulin-like growth factors in the CNS. Trends Neurosci 1988; 11: 107–111.

    Article  CAS  PubMed  Google Scholar 

  35. Woods SC, Lotter EC, McKay LD, Porte Jr D . Chronic intracerebroventricular infusion of insulin reduces food intake and body weight of baboons. Nature 1979; 282: 503–505.

    Article  CAS  PubMed  Google Scholar 

  36. Kahn SE, Prigeon RL, McCulloch DK, Boyko EJ, Bergman RN, Schwartz MW et al. Quantification of the relationship between insulin sensitivity and beta-cell function in human subjects. Evidence for a hyperbolic function. Diabetes 1993; 42: 1663–1672.

    Article  CAS  PubMed  Google Scholar 

  37. Figlewicz DP, Stein LJ, West D, Porte Jr D, Woods SC . Intracisternal insulin alters sensitivity to CCK-induced meal suppression in baboons. Am J Physiol 1986; 250 (5 Part 2): R856–R860.

    CAS  PubMed  Google Scholar 

  38. Feinle C, D’Amato M, Read NW . Cholecystokinin-A receptors modulate gastric sensory and motor responses to gastric distension and duodenal lipid. Gastroenterology 1996; 110: 1379–1385.

    Article  CAS  PubMed  Google Scholar 

  39. Feinle C, Grundy D, Otto B, Fried M . Relationship between increasing duodenal lipid doses, gastric perception, and plasma hormone levels in humans 1. Am J Physiol Regul Integr Comp Physiol 2000; 278: R1217–R1223.

    Article  CAS  PubMed  Google Scholar 

  40. Asakawa A, Inui A, Yuzuriha H, Ueno N, Katsuura G, Fujimiya M et al. Characterization of the effects of pancreatic polypeptide in the regulation of energy balance. Gastroenterology 2003; 124: 1325–1336.

    Article  CAS  PubMed  Google Scholar 

  41. Batterham RL, Le Roux CW, Cohen MA, Park AJ, Ellis SM, Patterson M et al. Pancreatic polypeptide reduces appetite and food intake in humans. J Clin Endocrinol Metab 2003; 88: 3989–3992.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Silvia Delgado-Aros and this study were supported by the Spanish National Institute of Health [Instituto de Salud ‘Carlos III’ (ISCIII)] (PI06/1405). Copyright 2010 PSMar.

Author information

Authors and Affiliations

  1. Neuro-Enteric Translational Science (NETS) group and Digestive Department of Hospital del Mar, Parc de Salut Mar Research Institute (IMIM-PSMar), Barcelona Biomedical Research Park (PRBB), Barcelona, Catalonia, Spain

    S Torra, L Ilzarbe, B Gras, M Andreu Garcia, F Bory Ros & S Delgado-Aros

  2. Digestive System Research Unit from Vall d’Hebron University Hospital, Barcelona, Catalonia, Spain

    J R Malagelada

  3. Nuclear Medicine Department from Vall d’Hebron University Hospital, Barcelona, Catalonia, Spain

    M Negre, A Mestre-Fusco & S Aguadé-Bruix

  4. Pharmacy Department from Vall d’Hebron University Hospital, Barcelona, Catalonia, Spain

    E Florensa & P Suñé

  5. Laboratori de Referència de Catalunya, Barcelona, Catalonia, Spain

    J J Hernandez

  6. Biochemistry and Molecular Genetics Department, Hospital Clínic, IDIBAPS, Universitat Autònoma de Barcelona, Barcelona, Catalonia, Spain

    R Casamitjana

Authors
  1. S Torra
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L Ilzarbe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J R Malagelada
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. M Negre
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. A Mestre-Fusco
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. S Aguadé-Bruix
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. E Florensa
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. P Suñé
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. B Gras
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. J J Hernandez
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. R Casamitjana
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. M Andreu Garcia
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. F Bory Ros
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. S Delgado-Aros
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S Delgado-Aros.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Torra, S., Ilzarbe, L., Malagelada, J. et al. Meal size can be decreased in obese subjects through pharmacological acceleration of gastric emptying (The OBERYTH trial). Int J Obes 35, 829–837 (2011). https://doi.org/10.1038/ijo.2010.210

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2010.210

Keywords

This article is cited by

Search

Advanced search

Quick links