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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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“that the weight loss itself results in altered hormone levels and increased satiety, since the 314 RYGB studies have not been able to draw inferences on causality due to their observational 315 nature (34-37).”
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Vidal, J., de Hollanda, A., & Jiménez, A. (2016) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2016.02.029 · Cited by 29
“subcutaneous administration of saline resulted in an increase in food intake in RYGB subjects but not in subjects that had undergone adjustable gastric banding (32) .”
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“Studies have shown gut hormones are important determinants or mediators for long-term weight loss post-surgery [61].”
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“Formal studies of appetite sensation before and after gastric bypass surgery are sparse but patients who have undergone obesity surgery report marked drops in hunger, as well as an earlier onset of meal-induced satiety.(56) In addition, we need studies assessing appetite in gastric bypass subjects to whom GLP-1 recept…”
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“In addition, an increase in gastrointestinal gut hor ones such as peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) could also play an important part due to their effects on the gastrointestinal system together with a diuretic and natriuretic effect on the kidney [35].”
BackgroundVisceral Obesity Is a Negative Predictor of Remission of Diabetes 1 Year After Bariatric Surgery
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“Weight loss after RYGB is most prominent in patients who exhibit the greatest postprandial excursions of peptide YY and glucagon-like peptide 1 hormones (22).”
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BackgroundAnti-Inflammatory Diets for Obesity and Diabetes
Sears, B. (2009) · Journal of the American College of Nutrition · doi:10.1080/07315724.2009.10718115 · Cited by 27
“This surgery not only causes calorie restriction, but also causes a significant increase in post-prandial peptide YY (PYY) secretion that is able to maintain satiety with reduced calorie intake [70,71].”
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BackgroundUpdates in weight loss surgery and gastrointestinal peptides
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“In particular the postprandial response of the incretin glucagon like peptide-1 (GLP-1) has been observed to be significantly influenced by RYGB (7).”
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“Alterations in the release of gastrointestinal (GI) peptides, known to modulate metabolism and food intake, after bypass surgery have been observed and proposed to contribute to the rapid improvement in glucose control [4].”
BackgroundBariatric surgery and nonalcoholic fatty liver disease
Bower, G., Athanasiou, T., Isla, A., Harling, L., Li, J. V., Holmes, E. C., Efthimiou, E., Darzi, A. W., & Ashrafian, H. (2015) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000000375 · Cited by 27
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“Additionally, an elevation of some gut hormones, such as GLP-1 and peptide YY, may cause a diuretic and natriuretic effect on the kidney, contributing to hypertension remission [34].”
BackgroundReduced Phenytoin Levels in an Epileptic Patient following Roux-En-Y Gastric Bypass for Obesity
Pournaras, D. J., Footitt, D., Mahon, D., & Welbourn, R. (2010) · Obesity Surgery · doi:10.1007/s11695-010-0107-1 · Cited by 25
“Recently, it has been shown that the mechanism is partly due to profound loss of appetite in association with increased satiety gut hormone concentrations [ 3 ].”
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Gastrointestinal Symptoms and Diseases Related to Obesity: An Overview
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Grueneberger, J. M., Karcz-Socha, I., Marjanović, G., Kuesters, S., Żwirska-Korczala, K., Schmidt, K., & Karcz, W. K. (2014) · BMC Surgery · doi:10.1186/1471-2482-14-20 · Cited by 24
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“Intravenous infusion of peptide YY(3-36) potently inhibits food intake in rats.”
BackgroundMethodInfluentialThe role of bariatric surgery in the treatment of diabetes
Tham, J. C., Howes, N., & le Roux, C. W. (2014) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622313513313 · Cited by 25
Urinary sodium excretion after gastric bypass surgery
Docherty, N. G., Fändriks, L., le Roux, C. W., Hallersund, P., & Werling, M. (2017) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2017.04.002 · Cited by 22
Self-citationGuerrero-Hreins, E., Foldi, C. J., Oldfield, B. J., Stefanidis, A., Sumithran, P., & Brown, R. M. (2022) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-021-09696-4 · Cited by 21
“The mechanisms driving decreased taste-detection thresholds and taste-induced reward is unknown but may involve changes in postprandial gut hormones, GLP-1 and PYY, which increase after RYGB and VSG compared with sham operated control rats [72, 73] and can modify VTA signalling [74].”
BackgroundBariatric surgery and hypertension: implications and perspectives after the GATEWAY randomized trial
Benaiges, D., Climent, E., Goday, A., Roux, J. A. F., & Pedro‐Botet, J. (2019) · Cardiovascular Diagnosis and Therapy · doi:10.21037/cdt.2018.10.04 · Cited by 24
“In addition, an increase in gastrointestinal gut hormones such as peptide YY and glucagon-like peptide-1 could also be involved in hypertension remission, due to their effects both on the gastrointestinal system together with a diuretic and natriuretic effect on the kidney (15).”
BackgroundCombination gut hormones: prospects and questions for the future of obesity and diabetes therapy
Khoo, B. C. E., & Tan, T. (2020) · Journal of Endocrinology · doi:10.1530/joe-20-0119 · Cited by 23
Peripheral mechanisms in the control of appetite and related experimental therapies in obesity
Camilleri, M. (2009) · Regulatory Peptides · doi:10.1016/j.regpep.2009.04.011 · Cited by 23
“The consistent findings are: reduced ghrelin (if part of stomach resected or out of contact with ingested nutrient), and early appearance and higher values of glucose counterregulatory hormones (like insulin, GIP, and GLP-1) and ileal hormones involved in the ileal brake, predominantly PYY [20].”
BackgroundInfluentialTang, T., Abbott, S., le Roux, C. W., Wilson, V., Singhal, R., Bellary, S., & Tahrani, A. A. (2017) · Diabetes Obesity and Metabolism · doi:10.1111/dom.13131 · Cited by 22
Eskandaros, M. S., & Abbass, A. (2022) · Obesity Surgery · doi:10.1007/s11695-021-05868-y · Cited by 22
Nymo, S., Skjølsvold, O. B., Aukan, M. I., Finlayson, G., Græslie, H., Mårvik, R., Kulseng, B. E., Sandvik, J., & Martins, C. (2022) · Obesity Surgery · doi:10.1007/s11695-022-06075-z · Cited by 24
Posovszky, C., & Wabitsch, M. (2015) · Hormone Research in Paediatrics · doi:10.1159/000369555 · Cited by 23
Seyfried, F., Bueter, M., Spliethoff, K., Miras, A. D., Abegg, K., Lutz, T. A., & le Roux, C. W. (2014) · Obesity Surgery · doi:10.1007/s11695-014-1301-3 · Cited by 22
“The available data on ghrelin levels after RYGB in humans are inconclusive, as decreased [38], unchanged [39, 40] or even increased [41, 42] levels have been observed postoperatively.”
BackgroundGatmaitan, P., Huang, H., Talarico, J. A., Moustarah, F., Kashyap, S. R., Kirwan, J. P., Schauer, P. R., & Brethauer, S. A. (2010) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2010.05.018 · Cited by 22
Physiology, pathophysiology and therapeutic implications of enteroendocrine control of food intake
Elliott, J. A., Reynolds, J. V., le Roux, C. W., & Docherty, N. G. (2016) · Expert Review of Endocrinology & Metabolism · doi:10.1080/17446651.2016.1245140 · Cited by 22
“mally accompany reduced energy intake [273].”
Liaskos, C., Koliaki, C. C., Αλεξιάδου, Κ., Argyrakopoulou, G., Tentolouris, N., Diamantis, T., Alexandrou, A. P., Katsilambros, N. L., & Kokkinos, A. D. (2018) · Obesity Surgery · doi:10.1007/s11695-018-3454-y · Cited by 22
Gender as a Deterministic Factor in Procedure Selection and Outcomes in Bariatric Surgery
Bal, J., Ilonzo, N., Adediji, T., & Leitman, I. M. (2021) · JSLS Journal of the Society of Laparoscopic & Robotic Surgeons · doi:10.4293/jsls.2020.00077 · Cited by 22
“During LRYGB, the duodenum, gastric fundus, and body of the stomach are bypassed, which results in restricted gastric capacity and reduced nutrient and caloric absorption.(1) During LSG the greater curvature and fundus of the stomach are resected, essentially creating a tube of the stomach.”
BackgroundDiet shapes the metabolite profile in the intact human ileum, which affects PYY release
Dagbasi, A., Byrne, C., Blunt, D. M., Serrano-Contreras, J. I., Becker, G. F., Blanco, J. M., Camuzeaux, S., Chambers, E. S., Danckert, N. P., Edwards, C. H., et al. (2024) · Science Translational Medicine · doi:10.1126/scitranslmed.adm8132 · Cited by 20
“Roux-en Y gastric bypass (RYGB) surgery, which is associated with expedited and increased delivery of nutrients to the ileum, also increases PYY and GLP-1 release and reduces energy intake and body weight in humans ( 10 ).”
Backgroundde Oliveira, L. F., Tisott, C. G., Silvano, D. M., Campos, C. M. M., & do Nascimento, R. R. (2015) · ABCD Arquivos Brasileiros de Cirurgia Digestiva (São Paulo) · doi:10.1590/s0102-6720201500s100009 · Cited by 20
Mihmanlı, M., Işıl, R. G., Işıl, C. T., Ömeroğlu, S., Sayın, P., Oba, S., Öztürk, F. Y., & Altuntaş, Y. (2017) · Obesity Surgery · doi:10.1007/s11695-017-2747-x · Cited by 21
“area in this type of surgery, changes in gut hormone concentrations may cause calcium (Ca) and 25-OH-vitamin-D3 (vitD) insufficiency in patients who undergo LSG [6].”
BackgroundOertel, M., Ziegler, C. G., Kohlhaas, M., Nickel, A. G., Kloock, S., Maack, C., Sequeira, V., Faßnacht, M., & Dischinger, U. (2024) · Endocrine Connections · doi:10.1530/ec-23-0398 · Cited by 21
“Elevated levels of glucagon-like peptide 1 (GLP-1), peptide tyrosine tyrosine (PYY), glucose-dependent insulinotropic polypeptide (GIP) and oxyntomodulin were found following bariatric surgery (15, 16, 17, 18).”
BackgroundInfluentialHunt, K. F., Dunn, J., le Roux, C. W., Reed, L. J., Marsden, P. K., Patel, A. G., & Amiel, S. A. (2016) · Diabetes Care · doi:10.2337/dc15-2721 · Cited by 21
“ad libitum consumption after RYGB (6,35).”
BackgroundMethodThe role of gut hormones in the pathogenesis and management of obesity
Makaronidis, J., & Batterham, R. L. (2019) · Current Opinion in Physiology · doi:10.1016/j.cophys.2019.04.007 · Cited by 22
Tan, Y. W., Shang, M., Davis, S., & Gananadha, S. (2025) · Langenbeck s Archives of Surgery · doi:10.1007/s00423-025-03831-4 · Cited by 21
“However, pharmacotherapy, par - ticularly GLP-1 agonists, has gained increasing attention in recent years due to their beneficial hormonal effects on satiety and hunger regulation [30, 31].”
Physiology of Energy Intake in the Weight‐Reduced State
Berthoud, H., Seeley, R. J., & Roberts, S. B. (2021) · Obesity · doi:10.1002/oby.23080 · Cited by 23
“Second, bariatric surgery is the most effective weight loss intervention on average, and this effect cannot be easily attributed to mechanical restriction and malabsorption because patients report being less hungry even after substantial weight has been lost (19).”
BackgroundPatient Motivations and Goals for Bariatric Surgery: A Mixed Methods Study
Ahlich, E. M., Verzijl, C. L., Cunning, A., Wright, E., & Rancourt, D. (2021) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2021.05.017 · Cited by 20
Elhag, W., Lock, M., & Ansari, W. E. (2023) · Obesity Surgery · doi:10.1007/s11695-023-06528-z · Cited by 20
Diabetes Remission Following Metabolic Surgery: Is GLP-1 the Culprit?
Vidal, J., & Jiménez, A. (2013) · Current Atherosclerosis Reports · doi:10.1007/s11883-013-0357-1 · Cited by 20
Netto, B. D. M., Earthman, C. P., Bettini, S. C., Clemente, A. P. G., Masquio, D. C. L., Farias, G., Boritza, K. C., da Silva, L. G., von der Heyde, M. E., & Dâmaso, A. R. (2016) · European Journal of Gastroenterology & Hepatology · doi:10.1097/meg.0000000000000665 · Cited by 20
Hutch, C. R., & Sandoval, D. A. (2016) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13194 · Cited by 21
Dai, X., Zhao, W., Zhan, J., Zeng, S.-H., Ran, D., Zhang, H., Song, Z., Song, K. H., & Wu, L. (2016) · International Immunopharmacology · doi:10.1016/j.intimp.2016.11.033 · Cited by 23
Christensen, B., Schmidt, J. B., Nielsen, M. S., Tækker, L., Holm, L., Lunn, S., Bredie, W. L. P., Ritz, C., Holst, J. J., Hansen, T. F., et al. (2018) · Contemporary Clinical Trials Communications · doi:10.1016/j.conctc.2018.02.002 · Cited by 20
Effect of sleeve gastrectomy on hypertension
Samson, R., Milligan, G. P., Lewine, E. B., Sindi, F., Garagliano, J. M., Fernandez, C., Moore, R., DuCoin, C. G., Oparil, S., & Jemtel, T. H. L. (2018) · Journal of the American Society of Hypertension · doi:10.1016/j.jash.2018.09.007 · Cited by 20
Recent Advances in the Neurobiology of Altered Motivation Following Bariatric Surgery
Brutman, J. N., SIROHI, S. K., & Davis, J. F. (2019) · Current Psychiatry Reports · doi:10.1007/s11920-019-1084-2 · Cited by 20
Nudotor, R. D., Canner, J. K., Haut, E. R., Prokopowicz, G. P., & Steele, K. E. (2020) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2020.09.035 · Cited by 20
Laurenius, A., & Engström, M. (2016) · Clinical Obesity · doi:10.1111/cob.12158 · Cited by 25
“remain overweight or even obese, and many are still struggling to limit their energy intake in the long term (33,46).”
BackgroundObesity surgery: happy with less or eternally hungry?
Shin, A. C., & Berthoud, H. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2012.11.009 · Cited by 19
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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