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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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Nuzzo, A., Czernichow, S., Hertig, A., Ledoux, S., Poghosyan, T., Quilliot, D., Gall, M. L., Bado, A., & Joly, F. (2021) · The Lancet. Gastroenterology & hepatology · doi:10.1016/s2468-1253(20)30331-9 · Cited by 115
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“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.”
BackgroundInfluentialChanges in gut hormones after bariatric surgery
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Altered brain activity in severely obese women may recover after Roux-en Y gastric bypass surgery
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GLP-1 and Glucose Tolerance After Sleeve Gastrectomy in Morbidly Obese Subjects With Type 2 Diabetes
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“However, this view has been challenged by 1) studies in humans—performed long after RYGB using the GLP-1 receptor antagonist exendin (9-39) (Ex 9-39)— showing that blockade of GLP-1 action results in marked decrease in insulin secretion but limited impact on glucose tolerance (2,3); 2) data showing the GLP-1 response…”
MethodResultMakaronidis, J. M., Neilson, S., Cheung, W.-H., Tymoszuk, U., Pucci, A., Finer, N., Doyle, J., Hashemi, M., Elkalaawy, M., Adamo, M., et al. (2016) · Appetite · doi:10.1016/j.appet.2016.07.029 · Cited by 94
Valderas, J. P., Verónica Irribarra, P., Boza, C., de la Cruz, R., Yéssica Liberona, Z., Acosta, A. M., Yolito, M., & Alberto Maiz, G. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-0983 · Cited by 92
Reappraising the role of the vagus nerve in GLP-1-mediated regulation of eating
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“In humans and rodents, GLP-1 levels are reduced in obesity, while bariatric surgery dramatically increases post-prandial levels of GLP-1 (Chambers et al., 2014; Jiménez et al., 2014; Umeda et al., 2011) as early as a few days after the surgery (Le Roux et al., 2007).”
BackgroundGut adaptation after metabolic surgery and its influences on the brain, liver and cancer
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“Weight loss is due to decreased appetite and caloric intake rather than malabsorption [32].”
BackgroundSelf-citationThe Gut Hormones in Appetite Regulation
Suzuki, K., Jayasena, C. N., & Bloom, S. R. (2011) · Journal of Obesity · doi:10.1155/2011/528401 · Cited by 98
“Intriguingly, the mechanisms of long-term weight loss following bariatric surgery are yet to be determined; however several gut hormones have been implicated as contributory factors; a decrease in ghrelin and an increase in PYY and GLP-1 levels have been found following bypass surgery [19–21].”
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Nguyen, A., Herzog, H., & Sainsbury, A. (2011) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0b013e3283422f0a · Cited by 92
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“In two observational studies that stratified RYGBP patients according to weight loss response, the mean GLP-1 response was approximately 50% higher in the “good responders” than in the “poor responders,” with proportionate relative reductions in appetite (67, 74).”
Patients' Experiences of Weight Regain After Bariatric Surgery
Tolvanen, L., Christenson, A., Surkan, P. J., & Lagerros, Y. T. (2022) · Obesity Surgery · doi:10.1007/s11695-022-05908-1 · Cited by 87
“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].”
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Malik, S., Mitchell, J. E., Steffen, K. J., Engel, S. G., Wiisanen, R., Garcia, L., & Malik, S. A. (2015) · Obesity Research & Clinical Practice · doi:10.1016/j.orcp.2015.07.003 · Cited by 88
Changes in Gastrointestinal Hormones and Leptin After Roux‐en‐Y Gastric Bypass Surgery
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Leveraging the Gut to Treat Metabolic Disease
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“In one longitudinal study, significantly elevated GLP-1 and PYY responses to a mixed meal were apparent as early as 2 days after RYGB surgery [67].”
BackgroundShak, J. R., Roper, J., Perez-Perez, G. I., Tseng, C., François, F., Gamagaris, Z., Patterson, C., Weinshel, E. H., Fielding, G., Ren, C. J., et al. (2008) · Obesity Surgery · doi:10.1007/s11695-008-9454-6 · Cited by 83
“In contrast, after RYGB, fasting levels of GIP increase [46], and mealtime dynamics of GLP-1 change in a way that enhances satiety as reported in other studies [26, 47 ].”
ResultEspinós, J. C., Turró, R., Moragas, G., Bronstone, A., Buchwald, J. N., Mearin, F., Mata, A., Uchima, H., Turró, J., & Delgado-Aros, S. (2015) · Obesity Surgery · doi:10.1007/s11695-015-1863-8 · Cited by 83
“Studies have shown better long-term weight outcomes after RYGB or laparoscopic adjustable gastric band LAGB in patients with enhanced PYY postprandial response [29-31].”
The Gut Hormone Response Following Roux-en-Y Gastric Bypass: Cross-sectional and Prospective Study
Pournaras, D. J., Osborne, A., Hawkins, S. C., Mahon, D., Ghatei, M. A., Bloom, S. R., Welbourn, R., & le Roux, C. W. (2009) · Obesity Surgery · doi:10.1007/s11695-009-9989-1 · Cited by 82
“Finally, in a randomised double-blind saline controlled study of patients after RYGB and laparoscopic adjustable gastric banding (LAGB), inhibition of the gut hormone response with octeotride (a somatostatin analogue) increased food intake in the RYGB group, but not in the LAGB group, suggesting that gut hormones migh…”
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CD4+ T cells memorize obesity and promote weight regain
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“Several studies have examined fasting and postprandial gut peptides in morbidly obese patients after RYGB.(57,60,61) Korner et al noted an exaggerated postprandial insulin response and changes in ghrelin and PYY consistent with increased satiety as a mechanism of weight loss after RYGB.”
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“A large increase in postprandial GLP-1 immediately after RYGB has been definitively described by us (6) and others (7, 10, 12, 17), and is sustained in the long-term (2, 16, 32).”
BackgroundKoliaki, C. C., Liatis, S., Dalamaga, Μ., & Kokkinos, A. D. (2020) · Current Obesity Reports · doi:10.1007/s13679-020-00396-9 · Cited by 87
Taste-related reward is associated with weight loss following bariatric surgery
Smith, K., Papantoni, A., Veldhuizen, M. G., Kamath, V. J., Harris, C., Moran, T. H., Carnell, S., & Steele, K. E. (2020) · Journal of Clinical Investigation · doi:10.1172/jci137772 · Cited by 77
Intestinal feedback signaling and satiety
Moran, T. H., & Dailey, M. J. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.02.005 · Cited by 86
“Meal stimulated PYY and GLP-1 secretion are significantly elevated as early as 2 days postoperatively and remain elevated at a 6 week time point (84).”
BackgroundBariatric surgeries: beyond restriction and malabsorption
Sandoval, D. A. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.148 · Cited by 79
A Systematic Review and Meta-analysis of the Effect of Gastric Bypass Surgery on Plasma Lipid Levels
Carswell, K. A., Belgaumkar, A. P., Amiel, S. A., & Patel, A. G. (2015) · Obesity Surgery · doi:10.1007/s11695-015-1829-x · Cited by 78
“There is a global reduction in food intake [35–37], which has been linked to early satiety [38] and loss of appetite, associated with increased postprandial peptide tyrosine-tyrosine (PYY) and glucagon-like peptide 1 (GLP-1) levels [38–40].”
BackgroundChronaiou, A., Tsoli, M., Kehagias, I., Leotsinidis, M., Kalfarentzos, F. E., & Alexandrides, T. K. (2012) · Obesity Surgery · doi:10.1007/s11695-012-0738-5 · Cited by 79
Buhmann, H., le Roux, C. W., & Bueter, M. (2014) · Best Practice & Research Clinical Gastroenterology · doi:10.1016/j.bpg.2014.07.003 · Cited by 81
Regulation of body weight: Lessons learned from bariatric surgery
Albaugh, V. L., He, Y., Münzberg, H., Morrison, C. D., Yu, S., & Berthoud, H. (2022) · Molecular Metabolism · doi:10.1016/j.molmet.2022.101517 · Cited by 80
“[56] le Roux CW, Welbourn R, Werling M, Osborne A, Kokkinos A, Laurenius A, et al.”
BackgroundRole of Bile Acids in Bariatric Surgery
Wang, W., Cheng, Z., Wang, Y., Dai, Y., Zhang, X., & Hu, S. (2019) · Frontiers in Physiology · doi:10.3389/fphys.2019.00374 · Cited by 80
GLP-2 receptor in POMC neurons suppresses feeding behavior and gastric motility
Guan, X., Shi, X., Li, X., Chang, B. H., Wang, Y., Li, D., & Chan, L. (2012) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00245.2012 · Cited by 79
Factors affecting circulating levels of peptide YY in humans: a comprehensive review
Cooper, J. A. (2014) · Nutrition Research Reviews · doi:10.1017/s0954422414000109 · Cited by 77
“Further, inhibiting PYY results in an increase in both appetite and food intake in human subjects((57)).”
BackgroundPost metabolic bariatric surgery weight regain: the importance of GLP-1 levels
Başaran, N. Ç., Dotan, I., & Dicker, D. (2024) · International Journal of Obesity · doi:10.1038/s41366-024-01461-2 · Cited by 88
“They also reported that inhibiting GLP-1 and PYY responses by a somatostatin analog (octreotide) increased appetite and food intake [13].”
InfluentialCasajoana, A., Pujol, J., de Gordejuela, A. G. R., Elvira, J., Virgili, N. M., de Oca, F. J., Durán, X., Fernández‐Veledo, S., Vendrell, J. J., & Vilarrasa, N. (2017) · Obesity Surgery · doi:10.1007/s11695-017-2669-7 · Cited by 76
Papamargaritis, D., le Roux, C. W., Holst, J. J., & Davies, M. J. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvac176 · Cited by 73
“11,45 In the Swedish obese subjects (SOS) study, bariatric surgery was able to induce and maintain ≥ 15% mean WL over 20 years follow-up (compared with 1% WL at the usual care group).”
BackgroundSteffen, R., Potoczna, N., Bieri, N., & Horber, F. (2008) · Obesity Surgery · doi:10.1007/s11695-008-9675-8 · Cited by 69
“The finding that long-term resolution of metabolic syndrome depends upon weight loss, not the type of restrictive surgery by which it is achieved, offers a different perspective on a recent hypothesis that due to duodenal exclusion and related changes in gastrointestinal hormonal response to food ingestion gastric byp…”
BackgroundChanges in gut hormone profile and glucose homeostasis after laparoscopic sleeve gastrectomy
Papamargaritis, D., le Roux, C. W., Sioka, E., KOUKOULIS, G. N., Tzovaras, G. A., & Zacharoulis, D. (2012) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2012.08.007 · Cited by 72
“Additionally, there was a positive correlation at 12 months post-SG between the change at ODI (delta ODI) and weight loss for all the 3 indices that we have used (delta ODI [0–120], P 1⁄4 .”
BackgroundMethodInfluentialBanded Gastric Bypass: Better Long-Term Results? A Cohort Study with Minimum 5-Year Follow-Up
Lemmens, L. A. G. (2016) · Obesity Surgery · doi:10.1007/s11695-016-2397-4 · Cited by 70
Enteroendocrine hormones – central effects on behavior
Skibicka, K. P., & Dickson, S. L. (2013) · Current Opinion in Pharmacology · doi:10.1016/j.coph.2013.09.004 · Cited by 69
Type 2 diabetes mellitus—current therapies and the emergence of surgical options
Lebovitz, H. E. (2011) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2011.10 · Cited by 69
Impact of Obesity on Gynecology
Pandey, S., & Bhattacharya, S. (2010) · Women s Health · doi:10.2217/whe.09.77 · Cited by 70
“The ensuing changes alter peptides that may regulate appetite and satiety [115].”
BackgroundDo Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery?
Papamargaritis, D., & le Roux, C. W. (2021) · Nutrients · doi:10.3390/nu13030762 · Cited by 68
“In contrast, patients who had undergone AGB (an operation with minimal effect on gut hormones), did not exhibit changes in appetite or food intake with octreotide administration [19].”
BackgroundMethodResultInfluentialAppetite- and Weight-Regulating Neuroendocrine Circuitry in Hypothalamic Obesity
Gan, H., Cerbone, M., & Dattani, M. (2023) · Endocrine Reviews · doi:10.1210/endrev/bnad033 · Cited by 75
“The increase in PYY and GLP-1 secretion is thought to be a major factor in the sustained weight loss observed after gastric by-pass surgery (166, 167, 212).”
The CNS glucagon-like peptide-2 receptor in the control of energy balance and glucose homeostasis
Guan, X. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00096.2014 · Cited by 70
“GLP-1/2 are key 120 neuroendocrine signals for the gut-brain axis to control food intake and glucose 121 homeostasis(92); and proposed as important mediators for bariatric surgery-improved glycemic 122 control and insulin sensitivity (37; 47; 73; 74; 99; 121).”
BackgroundMechanisms of Disease: the role of gastrointestinal hormones in appetite and obesity
Vincent, R. P., Ashrafian, H., & le Roux, C. W. (2008) · Nature Clinical Practice Gastroenterology & Hepatology · doi:10.1038/ncpgasthep1118 · Cited by 71
“Studies have demonstrated that postprandial PYY and GLP-1 levels start rising as early as 2 days after the operation and can remain elevated for many months after surgery”
BackgroundShin, A. C., Zheng, H., & Berthoud, H. (2011) · Annals of Surgery · doi:10.1097/sla.0b013e31823e71b7 · Cited by 69
“001 and F[3,57] = 4.”
Mathes, C. M., Bueter, M., Smith, K., Lutz, T. A., le Roux, C. W., & Spector, A. C. (2011) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00214.2011 · Cited by 67
Mechanisms of surgical control of type 2 diabetes: GLP-1 is key factor
Holst, J. J., & Madsbad, S. (2016) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2016.02.033 · Cited by 65
“Similar observations were made by le Roux et al. in a series of studies from the Hammersmith Hospital, Imperial College, London [6,7].”
BackgroundInfluentialIntestinal GLP-1 and satiation: from man to rodents and back
Steinert, R. E., Beglinger, C., & Langhans, W. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.172 · Cited by 72
Weight Loss, Satiety, and the Postprandial Gut Hormone Response After Esophagectomy
Elliott, J. A., Docherty, N. G., Eckhardt, H., Doyle, S. L., Guinan, E. M., Ravi, N., Reynolds, J. V., & le Roux, C. W. (2016) · Annals of Surgery · doi:10.1097/sla.0000000000001918 · Cited by 69
Cui, Y., Elahi, D., & Andersen, D. K. (2011) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-011-1585-8 · Cited by 66
Nielsen, M. S., Ritz, C., Wewer Albrechtsen, N. J., Holst, J. J., le Roux, C. W., & Sjödin, A. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa061 · Cited by 65
Nunez, D. J., Bush, M., Collins, D. A., McMullen, S. L., Gillmor, D., Apseloff, G., Atiee, G. J., Corsino, L., Morrow, L., & Feldman, P. L. (2014) · PLoS ONE · doi:10.1371/journal.pone.0092494 · Cited by 65
“The post-prandial rises in PYY after gastric bypass surgery are comparable or somewhat greater than those seen with GSK263 when co-dosed with metformin, but the post-surgical increases in GLP-1 appear to be much greater [26–28].”
BackgroundCazzo, E., Pareja, J. C., Chaim, É. A., Geloneze, B., Barreto, M. R. L., & Magro, D. O. (2016) · Obesity Surgery · doi:10.1007/s11695-016-2345-3 · Cited by 66
Tolvanen, L., Svensson, Å., Hemmingsson, E., Christenson, A., & Lagerros, Y. T. (2020) · Obesity Surgery · doi:10.1007/s11695-020-05128-5 · Cited by 65
“between individuals, and over time, which may contribute to weight regain if appetite and portion sizes increases [8, 9].”
BackgroundAdipokines in the treatment of diabetes mellitus and obesity
Catalán, V., Gómez‐Ambrosi, J., Rodrı́guez, A., Salvador, J., & Frühbeck, G. (2009) · Expert Opinion on Pharmacotherapy · doi:10.1517/14656560802618811 · Cited by 65
“Active ghrelin levels have been shown to be decreased by the RYGBP procedure in obese patients [42,43] , whereas GLP-1 secretion has been reported to be increased [44] or decreased after the RYGBP procedure [45] .”
BackgroundGLP-1: A Mediator of the Beneficial Metabolic Effects of Bariatric Surgery?
Manning, S., Pucci, A. B. F., & Batterham, R. L. (2015) · Physiology · doi:10.1152/physiol.00027.2014 · Cited by 65
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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