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Gut Hormones as Mediators of Appetite and Weight Loss After Roux-en-Y Gastric Bypass
Abstract
In Brief Objective: To evaluate the physiologic importance of the satiety gut hormones. Background: Controversy surrounds the physiologic role of gut hormones in the control of appetite. Bariatric surgery remains the most effective treatment option for obesity, and gut hormones are implicated in the reduction of appetite and weight after Roux-en-Y gastric bypass. Methods: We correlated peptide YY (PYY) and glucagon-like peptide 1 (GLP-1) changes within the first week after gastric bypass with changes in appetite. We also evaluated the gut hormone responses of patients with good or poor weight loss after gastric bypass. Finally, we inhibited the gut hormone responses in gastric bypass patients and then evaluated appetite and food intake. Results: Postprandial PYY and GLP-1 profiles start rising as early as 2 days after gastric bypass (P < 0.05). Changes in appetite are evident within days after gastric bypass surgery (P < 0.05), and unlike other operations, the reduced appetite continues. However, in patients with poor weight loss after gastric bypass associated with increased appetite, the postprandial PYY and GLP-1 responses are attenuated compared with patients with good weight loss (P < 0.05). Inhibiting gut hormone responses, including PYY and GLP-1 after gastric bypass, results in return of appetite and increased food intake (P < 0.05). Conclusion: The attenuated appetite after gastric bypass is associated with elevated PYY and GLP-1 concentrations, and appetite returns when the release of gut hormones is inhibited. The results suggest a role for gut hormones in the mechanism of weight loss after gastric bypass and may have implications for the treatment of obesity. Roux-en-Y gastric bypass is an effective treatment for obesity, and gut hormones have been implicated as causing reduction of appetite and weight. We showed that significant weight loss depends on gut hormone concentrations and that attenuated appetite after gastric bypass is associated with increased gut hormones, and appetite returns when the release of gut hormones is inhibited.
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“GB subjects have elevated plasma concentrations of GLP-1 (6,8–13).”
From Gastric Bypass Surgery Enhances Glucagon-Like Peptide 1–Stimulated Postprandial Insulin Secretion in Humans (2011) · cites this paper as [10]
In the citing paper
“Genetic factors [8], increases in gut hormones such as glucagon-like-peptide-1 (GLP-1) and peptide YY (PYY) [9], and decreases in the production of ghrelin play an important role in appetite regulation and post-surgical weight outcomes [10].”
From Patients' Experiences of Weight Regain After Bariatric Surgery (2022) · cites this paper as [9]
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“When the rate of SI glucose delivery was ‘normalised’ to 4 kcal/min in RYGB subjects, the marked early rises of plasma glucosedependent insulinotropic polypeptide (GIP), GLP-1 and insulin, as well as GI symptoms, after a glucose drink were * Nam Q Nguyen quoc.nguyen@health.sa.gov.au 1 Department of Gastroenterology an…”
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“Alterations in the secretion of gastric and intestinal peptides, such as glucagon-like peptide-1 (GLP-1), ghrelin and YY peptide were demonstrated after RYGB [6,7].”
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“However, exendin-4’s effect waned after 17 days, and coadministration of PYY(3–36) and exendin-4 at various dosing combinations did not produce a more prolonged effect than the GLP-1 receptor agonist exendin-4 alone despite recent studies suggesting that chronic elevation in gut hormones PYY(3–36) and GLP-1 may cause…”
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“The gut hormones GLP-1, OXM, and PYY are elevated early after RYGB and stay elevated for years, whereas ghrelin levels tends to be reduced [54-58].”
BackgroundResultEndokrynne implikacje otyłości i zabiegów bariatrycznych
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Influence of diabetes surgery on gut hormones and incretins.
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“In a randomised trial, it was found that when patients were given somatostatin, which blocked peptide YY and glucagon-like peptide 1, they ate more when presented with a standard buffet meal, returning to their pre-bypass state((21)).”
Central Modulation of Energy Homeostasis and Cognitive Performance After Bariatric Surgery
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“Gut hormones, GLP-1, GIP, oxyntomodulin, and peptide YY lead to appetite suppression and reduced food intake, as well as increased energy expenditure [105].”
BackgroundFood Aversions in Women During The 2 Years After Roux-En-Y Gastric Bypass
Novais, P. F. S., Rasera, I., Shiraga, E. C., & de Oliveira, M. R. M. (2010) · Obesity Surgery · doi:10.1007/s11695-010-0342-5 · Cited by 16
Surgical Treatments for Obesity
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“Recently, special attention has been given to the role of the gut-brain axis (GBA) in the pathogenesis of obesity (le Roux et al., 2007).”
BackgroundEarly 24-hour blood pressure response to Roux-en-Y gastric bypass in obese patients
Pedersen, J. S., Borup, C., Damgaard, M., Yatawara, V. D., Floyd, A. K., Gadsbøll, N., & Bonfils, P. K. (2016) · Scandinavian Journal of Clinical and Laboratory Investigation · doi:10.1080/00365513.2016.1258725 · Cited by 16
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“…acid signaling and flow, gut microbiota, as well as several neurohormonal effects (through GLP-1, P-YY, Ghrelin, and leptin) play an important role in inducing many of the beneficial effects of bariatric surgery (le Roux et al., 2007; Stefater et al., 2012; Liou et al., 2013; Yan et al., 2014).”
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“Various types of bariatric surgery have been associated with increases in levels of the incretin glucagon-like peptide-1 (GLP-1) which promotes postprandial insulin secretion, suppresses glucagon secretion, and induces natriuresis, among other central effects [37].”
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“GLP-1 involvement in weight loss after surgery is still debated but elevated GLP-1 concentration is well correlated to the attenuated appetite after GBP, and in patients with poor decreased appetite, the postprandial GLP-1 response is attenuated [10].”
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BackgroundInfluentialEndocrine Function after Bariatric Surgery
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“In regards to postprandial ghrelin levels, most studies demonstrated similar responses to a mixed solid or liquid meal 2 days or 12 months after RYGB compared to con-trol subjects (68,74,144).”
Holst, J. J., Madsbad, S., Bojsen-Møller, K. N., Dirksen, C., & Svane, M. S. (2024) · Peptides · doi:10.1016/j.peptides.2024.171199 · Cited by 14
“Le Roux and coworkers [18] elegantly demonstrated, using infusions of the powerfully inhibitory hormone somato-statin, that inhibition of the hormonal responses was associated with increases in food intake after gastric bypass (but not after gastric banding), suggesting that one or more of these…”
BackgroundResultRegulation of Energy Homeostasis After Gastric Bypass Surgery
Yarmush, M. L., D'Alessandro, M. R., & Saeidi, N. (2017) · Annual Review of Biomedical Engineering · doi:10.1146/annurev-bioeng-071813-105140 · Cited by 14
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Gut Mucosal Gene Expression and Metabolic Changes After Roux‐en‐Y Gastric Bypass Surgery
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“Conversely, the unretarded transit of nutrients through the gastric pouch into the small intestine (as evident from the rapid absorption of acetaminophen) likely explains the increased postprandial secretion of CCK (22), neurotensin (23), PYY, and GLP-1 (24) after RYGB.”
BackgroundInfluentialPancreatic Polypeptide Meal Response May Predict Gastric Band-Induced Weight Loss
Dixon, A. F. R., le Roux, C. W., Ghatei, M. A., Bloom, S. R., McGee, T. L., & Dixon, J. B. (2011) · Obesity Surgery · doi:10.1007/s11695-011-0469-z · Cited by 14
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“On the contrary, there is good evidence showing that gut signaling after RYGB is essential for the weight loss effect of the procedure.(88,89) However, if the scien-”
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“…an increase PYY In addition, these areas are interconnected with the limbic system and regions of the cortex involved in reward control and stimulus perception, among other key functions for EI [89,90]. levels and a decrease in ghrelin levels compared to obesity or pre-surgery subjects [103–107].”
BackgroundGastrointestinal hormones and polycystic ovary syndrome
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Jørgensen, N. B., Bojsen-Møller, K. N., Dirksen, C., Martinussen, C., Svane, M. S., Kristiansen, V. B., Holst, J. J., & Madsbad, S. (2019) · Scientific Reports · doi:10.1038/s41598-019-51516-y · Cited by 12
Hyde, K. M., Blonde, G. D., Bueter, M., le Roux, C. W., & Spector, A. C. (2020) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00240.2019 · Cited by 12
Werling, M., Fändriks, L., Vincent, R. P., Cross, G. F., le Roux, C. W., & Olbers, T. (2014) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2014.04.018 · Cited by 12
“PYY [11,16,20].”
BackgroundMethodInfluentialStylopoulos, N., & Aguirre, V. (2009) · Gastrointestinal Endoscopy · doi:10.1016/j.gie.2009.01.022 · Cited by 12
The Role of Adipokines and Gastrointestinal Tract Hormones in Obesity
Świerczyński, J., & Śledziński, T. (2012) · Springer eBooks · doi:10.1007/978-3-642-02411-5_6 · Cited by 12
Does the ileal brake mechanism contribute to sustained weight loss after bariatric surgery?
Barreto, S. G., Soenen, S., Chisholm, J. A., Chapman, I. M., & Kow, L. (2017) · ANZ Journal of Surgery · doi:10.1111/ans.14062 · Cited by 13
“Human studies have clearly demonstrated weight regain following pharmacologically inhibited PYY and GLP-1 levels in post-bariatric surgery patients.(58) One of the most significant predictors of weight regain following surgery is an increased ‘food urge’ or appetite.”
BackgroundBojsen-Møller, K. N., Svane, M. S., Martinussen, C., Dirksen, C., Jørgensen, N. B., Jensen, J.-E. B., Jensen, C. Z., Torekov, S. S., Kristiansen, V. B., Rehfeld, J. F., et al. (2023) · International Journal of Obesity · doi:10.1038/s41366-023-01372-8 · Cited by 13
“…concentration was lower in the primary WL failure group as also observed in previous WL response studies [14, 18, 19], consistent with the higher body weight [27], but the postprandial suppression of ghrelin did not differ between the groups contrasting with previous fi ndings [10, 14, 18, 19].”
BackgroundResultInfluentialDagbasi, A., Fuller, A., Hanyaloglu, A. C., Carroll, B., McLaughlin, J. T., Frost, G. S., & Holliday, A. (2024) · Appetite · doi:10.1016/j.appet.2024.107718 · Cited by 11
Aukan, M. I., Rehfeld, J. F., Holst, J. J., & Martins, C. (2024) · International Journal of Obesity · doi:10.1038/s41366-024-01658-5 · Cited by 11
“The mechanisms behind its success are not clearly understood, but changes in the homeostatic appetite control system, including reductions in the orexigenic hormone ghrelin and increased postprandial secretion of satiety gut peptides have been considered key mediators [6, 7].”
Voermans, B., Gerdes, V. E. A., & Nieuwdorp, M. (2025) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2025.2512551 · Cited by 12
“Importantly, post-prandial GLP-1 levels have been linked to differences in long-term outcomes post-bariatric surgery in several studies, possibly explaining the slight increase in efficacy of RYGB for long-term weight loss [93–95].”
Abdallah, H., Klink, W. H., Derienne, J., Voican, C. S., Perlemuter, G., Courie, R., Dagher, I., & Tranchart, H. (2025) · Obesity Surgery · doi:10.1007/s11695-025-08210-y · Cited by 16
“Nevertheless, it was demonstrated that inadequate weight loss after BS is often associated with increased appetite and an unfavorable postoperative gut hormone profile, including reduced circulating GLP-1 levels [25, 26].”
Ting, C.-H., Syu, Y.-F., Chen, L.-Y., Lee, F., Lee, S., Lee, W., & Chen, C.-Y. (2015) · Nutrition · doi:10.1016/j.nut.2015.07.006 · Cited by 11
Chirurgie als pluripotentes Instrument gegen eine metabolische Erkrankung
Corteville, C., Faßnacht, M., & Bueter, M. (2014) · Der Chirurg · doi:10.1007/s00104-014-2796-9 · Cited by 11
Secretin as a Satiation Whisperer With the Potential to Turn into an Obesity-curbing Knight
Schnabl, K., Li, Y., U-Din, M., & Klingenspor, M. (2021) · Endocrinology · doi:10.1210/endocr/bqab113 · Cited by 11
Blonde, G. D., Price, R. K., le Roux, C. W., & Spector, A. C. (2021) · Nutrients · doi:10.3390/nu13113856 · Cited by 13
Sridhar, A., Khan, D., Abdelaal, M., Elliott, J. A., Naughton, V. R., Flatt, P. R., le Roux, C. W., Docherty, N. G., & Moffett, R. C. (2022) · PLoS ONE · doi:10.1371/journal.pone.0274788 · Cited by 11
Brethvad, A. O., Zakariassen, H. L., Holt, J., Lundgren, J. R., Jakobsen, A., Hartmann, B., Lehmann, E. W., Kissow, H., Holst, J. J., Madsbad, S., et al. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155534 · Cited by 9
“The underlying mechanisms responsible for weight regain after diet-induced weight loss remain unclear [40,41], and very little is known about the hormonal regulation following diet-induced weight loss [42 – 44].”
BackgroundCarmody, J. S., Ahmad, N. N., Machineni, S., Lajoie, S., & Kaplan, L. M. (2015) · Endocrinology · doi:10.1210/en.2015-1226 · Cited by 11
“In the mouse, increased energy expenditure drives most of the weight loss after RYGB (20, 34, 35), whereas the postoperative weight loss in human patients is due primarily to decreased food intake (36, 37).”
BackgroundNovel approaches to anti-obesity drug discovery with gut hormones over the past 10 years
Rose, F., Bloom, S. R., & Tan, T. (2019) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2019.1646243 · Cited by 11
“peptide YY, and this is thought to drive many of the metabolic benefits of this intervention [14,15]; thirdly, the suppression of”
BackgroundGastrointestinal peptides after bariatric surgery and appetite control: are they in tuning?
Doucet, É. (2008) · Current Opinion in Clinical Nutrition & Metabolic Care · doi:10.1097/mco.0b013e32830ab9c9 · Cited by 11
Stanley, C., Mallik, R., Hamid, N., Jassil, F. C., Reuven, V., Ruwona, T., Dicken, S. J., Qamar, S., Norton, B. C., Kingett, H., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04416-4 · Cited by 10
From pathophysiology to novel approaches for obesity-associated hypertension
Kanbay, M., Yayci, E., Genc, C., Çöpür, S., Aktaş, Ö. Y., Sarafidis, P. A., Covic, A. C., Ortíz, A., & Laffin, L. J. (2025) · Clinical Kidney Journal · doi:10.1093/ckj/sfaf218 · Cited by 10
“Additionally, incretins such as GLP-1 and peptide YY may increase and induce natriuresis [99 ] or regulate the SNS through receptors at the area postrema [100 ].”
Factors associated with hypertension remission after gastrectomy for gastric cancer patients
Kang, B., Liu, X., Cheng, Y.-X., Tao, W. Y., & Peng, D. (2022) · World Journal of Gastrointestinal Surgery · doi:10.4240/wjgs.v14.i8.743 · Cited by 10
Regulación del apetito: bases neuroendocrinas e implicaciones clínicas
Palma, J., & Iriarte, J. (2012) · Medicina Clínica · doi:10.1016/j.medcli.2011.11.024 · Cited by 15
The role of glucagon‑like peptide 1 in glucose homeostasis and in other aspects of human physiology
Franek, E., Gajos, G., Gumprecht, J., Kretowski, A. J., Zahorska‐Markiewicz, B., & Malecki, M. T. (2009) · Polskie Archiwum Medycyny Wewnętrznej · doi:10.20452/pamw.829 · Cited by 11
Vettermann, F. J., Rullmann, M., Becker, G., Luthardt, J., Zientek, F., Patt, M., Meyer, P., McLeod, A., Brendel, M., Blüher, M., et al. (2018) · European Journal of Nuclear Medicine and Molecular Imaging · doi:10.1007/s00259-018-4002-7 · Cited by 10
Mangan, A., Al‐Najim, W., McNamara, N. B., Martin, W. P., Antanaitis, A., Bleiel, S. B., Kent, R. M., le Roux, C. W., & Docherty, N. G. (2019) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01697 · Cited by 10
Al-Rasheid, N., Gray, R. P., Sufi, P. A., Marina, N., Alsayrafi, M., Denver, A. E., & Mohamed‐Ali, V. (2014) · Obesity Surgery · doi:10.1007/s11695-014-1507-4 · Cited by 10
“However, octreotide also suppresses other gut hormones, such as PYY, which also decreases appetite and increases weight loss and are increased after RYGB surgery [18].”
BackgroundRYGB progressively increases avidity for a low-energy, artificially sweetened diet in female rats
Geary, N., Bächler, T., Whiting, L., Lutz, T. A., & Asarian, L. (2015) · Appetite · doi:10.1016/j.appet.2015.11.029 · Cited by 10
“RYGB patients endorsed less pre-meal hunger in comparison with their presurgical ratings in three studies (Borg et al., 2006; le Roux et al., 2007; Morinigo et al., 2006), which appears inconsistent with our hunger interpretation.”
ResultGastrointestinal Endocrinology in Bariatric Surgery
Wabitsch, M. (2017) · Endocrine development · doi:10.1159/000475735 · Cited by 11
Disordered eating and weight loss after bariatric surgery
Gradaschi, R., Molinari, V., Sukkar, S. G., Negri, P. D., Adami, G. F., & Camerini, G. B. (2019) · Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity · doi:10.1007/s40519-019-00749-x · Cited by 10
Management of hyperglycaemia in people with obesity
Mourougavelou, V., & Chowdhury, T. A. (2023) · Clinical Medicine · doi:10.7861/clinmed.2023-0135 · Cited by 10
Metadata
- Authors
- le Roux, C. W., Welbourn, R., Werling, M., Osborne, A., Kokkinos, A., Laurenius, A., Lönroth, H., Fändriks, L., Ghatei, M. A., Bloom, S. R., & Olbers, T.
- Affiliations
- Musgrove Park Hospital (GB)
- Sahlgrenska University Hospital (SE)
- Hammersmith Hospital (GB)
- Corresponding author
- Kokkinos, Alexander
- Ghatei, Mohammad A.
- Bloom, Stephen R.
- ORCID
- Venue
- Annals of Surgery
- Published
- 2007-11
- Volume
- 246
- Issue
- 5
- Pages
- 780-785
- ISSN
- 0003-4932 (ISSN-L)
- OpenAlex
- W2079737026
- Cited by
- 741
- References
- 31
- Citations by year
- 2026: 20 · 2025: 20 · 2024: 28 · 2023: 25 · 2022: 28 · 2021: 49 · 2020: 36 · 2019: 38 · 2018: 35 · 2017: 38 · 2016: 53 · 2015: 61 · 2014: 49 · 2013: 45 · 2012: 63
- FWCI
- 34.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Surgery (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute for Health and Care Research (DHCS/05/05)
- Topics
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Pharmacology (medical) › Pharmacology and Obesity Treatment
- Keywords
- gastrointestinal hormones, appetite regulation, Roux-en-Y gastric bypass, peptide YY, glucagon-like peptide-1, satiety, weight loss, obesity, postprandial hormone response, dietary intake, bariatric surgery
- MeSH terms
- Appetite Regulation, Female, Follow-Up Studies, Humans, Male, Middle Aged, Obesity, Morbid, Prospective Studies, Gastric Bypass, Weight Loss, Body Mass Index, Treatment Outcome, Peptide YY, Glucagon-Like Peptide 1, Ghrelin
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