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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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“Although these associations do not prove causality, inhibition of gut hormone release by administration of somatostatin increased appetite and food intake in bypass but not in band subjects, suggesting that gut hormones are more likely to mediate reduced appetite and food intake after RYGB (24).”
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“For example, a decrease in circulating ghrelin and an increase in peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) levels have been found following bypass surgery [15-17].”
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“However, recent observations were in disagreement with this hypothesis (Korner et al., 2005; le Roux et al., 2007; Reinehr et al., 2007).”
BackgroundResultBariatric surgery for type 2 diabetes
Dixon, J. B., le Roux, C. W., Rubino, F., & Zimmet, P. (2012) · The Lancet · doi:10.1016/s0140-6736(12)60401-2 · Cited by 299
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“For example, one 2007 study showed that meal-induced GLP-1 (and peptide YY [PYY]) excursions are higher in RYGB patients with superior weight loss compared with those who did not achieve sufficient weight loss (16).”
BackgroundRegulation of Glucose Homeostasis by GLP-1
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“Delivery to the jejunum of undigested chime of higher pH could enhance PYY and GLP-1 response to the meal, inducing satiety [24, 41, 42].”
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“One mechanism postulated to improve diabetes after gastric bypass is an augmented incretin response; postprandial plasma concentrations of the potent incretin glucagon-like peptide-1 rise after gastric bypass [2].”
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“In the case of the postprandial increase in PYY and GLP-1 levels and decrease in ghrelin, previous studies have consistently shown that these can be accurately assessed by sampling protocols similar to ours (9).”
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Gastric bypass reduces fat intake and preference
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“Consistent with this hypothesis, post-surgical increases in prandial GLP-1 are associated with greater insulin release (Umeda et al., 2011) and greater weight loss (le Roux et al., 2007) after RYGB surgery in humans.”
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“This hypothesis is supported by three lines of evidence: first, the administration of the somatostatin analogue octreotide to people following RYGB leads to increased appetite and energy intake, and weight gain [66]; second, combined administration of di-peptidyl peptidase inhibitor (DPP4) inhibitor and exendin 9-39 (…”
MethodAppetite regulation and weight control: the role of gut hormones
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Peripheral Mechanisms in Appetite Regulation
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“They suggested that gut hormones have a role to play in the mechanism of weight loss after gastric bypass, through their effects on appetite (38).”
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“Continued 578 April2010 Volum e 110 Num ber 4 Hormones measured Limb length Study groups Time points Measurements Summary Ghrelin, PYY, GLP-1 (49) Not reported Group 1: RYGB (n"8, 8 F); Group 2: GB (n"6, 6 F); Group 3: nonoperated weight matched to post-op RYGB and GB (n"8, 8 F) Post-op only (RYGB: 9 to 48 mo post-op;…”
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“le Roux and colleagues (70) reported that postprandial PYY and GLP-1 levels increased as early as 2 days after RYGB.”
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Scheithauer, T. P. M., Dallinga-Thie, G. M., de Vos, W. M., Nieuwdorp, M., & van Raalte, D. H. (2016) · Molecular Metabolism · doi:10.1016/j.molmet.2016.06.002 · Cited by 188
“Bariatric surgery was associated with increased PYY and GLP-1 levels post surgery, explaining, to some degree, the weight reduction due to higher satiety signals [149].”
BackgroundGLP-1: Molecular mechanisms and outcomes of a complex signaling system
Smith, N. K., Hackett, T. A., Galli, A., & Flynn, C. R. (2019) · Neurochemistry International · doi:10.1016/j.neuint.2019.04.010 · Cited by 204
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“GLP-1 is a powerful hormone whose ability to stimulate insulin secretion and normalize glucose levels has been widely documented, and GLP-1 levels increase after bariatric surgery.((20,44,45)) Surprisingly, it has been reported that the GLP-1 receptor is not required for DING ET AL.”
BackgroundSignalling from the periphery to the brain that regulates energy homeostasis
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“Suppression of the release of gut hormones such as PYY and GLP-1 with the somatostatin analogue octreotide after RYGB reverses the enhanced satiety and increases food intake acutely.(39) Although there may be additional satiety factors that contribute to reduced food intake after RYGB, taken together, these observatio…”
BackgroundSelf-citationFood Intake and Eating Behavior After Bariatric Surgery
Al‐Najim, W., Docherty, N. G., & le Roux, C. W. (2018) · Physiological Reviews · doi:10.1152/physrev.00021.2017 · Cited by 185
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Changes in Eating Behaviour and Meal Pattern Following Roux-En-Y Gastric Bypass
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“It is possible that RYGP leads to an altered microbial composition that regulates enteroendocrine function.”
BackgroundInfluentialMokadem, M., Zechner, J. F., Margolskee, R. F., Drucker, D. J., & Aguirre, V. (2013) · Molecular Metabolism · doi:10.1016/j.molmet.2013.11.010 · Cited by 181
“Third, administration of octreotide to patients after RYGB inhibits the secretion of GLP-1 (and other gut hormones), and also decreases satiety and increases food intake [5].”
BackgroundGLP-1 receptor signaling is not required for reduced body weight after RYGB in rodents
Ye, J., Hao, Z., Mumphrey, M. B., Townsend, R. L., Patterson, L. M., Stylopoulos, N., Münzberg, H., Morrison, C. D., Drucker, D. J., & Berthoud, H. (2014) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00491.2013 · Cited by 174
Alterations of sucrose preference after Roux-en-Y gastric bypass
Bueter, M., Miras, A. D., Chichger, H., Fenske, W. K., Ghatei, M. A., Bloom, S. R., Unwin, R. J., Lutz, T. A., Spector, A. C., & le Roux, C. W. (2011) · Physiology & Behavior · doi:10.1016/j.physbeh.2011.07.025 · Cited by 183
“37 confirmed that gastric bypass in rats, as in humans, leads to increased postprandial levels of GLP-1 and PYY [42,43].”
InfluentialMetabolic surgery: the role of the gastrointestinal tract in diabetes mellitus
Rubino, F., R'bibo, S. L., del Genio, F., Mazumdar, M., & McGraw, T. E. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2009.268 · Cited by 173
Bowels control brain: gut hormones and obesity
Field, B. C. T., Chaudhri, O. B., & Bloom, S. R. (2010) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2010.93 · Cited by 172
“48 Rodent studies also provide evidence of an anorectic synergy when IAPP is coadministered with either PYY(3-36) or cholecystokinin (CCK).”
The role of the gut/brain axis in modulating food intake
Sam, A. H., Troke, R., Tan, T., & Bewick, G. A. (2011) · Neuropharmacology · doi:10.1016/j.neuropharm.2011.10.008 · Cited by 180
“Post-prandial PYY and GLP-1 levels begin to rise as early as 2 days following gastric bypass in humans (le Roux et al., 2007), and secretory products of enteroendocrine L cells, including PYYandGLP1 remainelevated twoyears after bypass surgery (leRouxet al., 2010).”
BackgroundMeal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery
Zheng, H., Shin, A. C., Lenard, N. R., Townsend, R. L., Patterson, L. M., Sigalet, D. L., & Berthoud, H. (2009) · American Journal of Physiology-Regulatory, Integrative and Comparative Physiology · doi:10.1152/ajpregu.00343.2009 · Cited by 165
“mones such as PYY, GLP-1, and amylin, and/or enhanced meal-induced suppression of ghrelin secretion, in a caloriedependent manner (15, 16, 21, 22).”
BackgroundGastrointestinal hormones and bariatric surgery-induced weight loss
Ionut, V., Burch, M. A., Youdim, A., & Bergman, R. N. (2013) · Obesity · doi:10.1002/oby.20364 · Cited by 162
“Blockade of gut hormone release with somatostatin during a meal increased food intake in a the GB group but not in a weight loss matched gastric banding group, suggesting that the GLP-1 response contributes to changes in food intake in the GB group, but not in the banding group (24).”
BackgroundInfluentialMechanism Underlying the Weight Loss and Complications of Roux-en-Y Gastric Bypass. Review
Abdeen, G., & le Roux, C. (2016) · Obesity Surgery · doi:10.1007/s11695-015-1945-7 · Cited by 162
“peripheral effects on glycaemia and food intake [52, 75, 204] has given new insight into the physiological changes that take”
BackgroundCampos, G. M., Rabl, C., Peeva, S., Ciovica, R., Rao, M. N., Schwarz, J., Havel, P. J., Schambelan, M., & Mulligan, K. M. (2009) · Journal of Gastrointestinal Surgery · doi:10.1007/s11605-009-1060-y · Cited by 160
Clinical relevance of the bile acid receptor TGR5 in metabolism
van Nierop, F. S., Scheltema, M. J. V., Eggink, H. M., Pols, T. W. H., Sonne, D. P., Knop, F. K., & Soeters, M. R. (2016) · The Lancet Diabetes & Endocrinology · doi:10.1016/s2213-8587(16)30155-3 · Cited by 163
Søvik, T. T., Taha, O., Aasheim, E. T., Engström, M., Kristinsson, J., Björkman, S., Schou, C. F., Lönroth, H., Mala, T., & Olbers, T. (2010) · Journal of British Surgery · doi:10.1002/bjs.6802 · Cited by 155
Molecular mechanisms underlying nutrient-stimulated incretin secretion
Parker, H. E., Reimann, F., & Gribble, F. M. (2010) · Expert Reviews in Molecular Medicine · doi:10.1017/s146239940900132x · Cited by 155
Increased Risk of Colorectal Cancer After Obesity Surgery
Derogar, M., Hull, M. A., Kant, P., Östlund, M. P., Lu, Y., & Lagergren, J. (2013) · Annals of Surgery · doi:10.1097/sla.0b013e318288463a · Cited by 155
Crosstalk between glucagon-like peptide 1 and gut microbiota in metabolic diseases
Zeng, Y., Wu, Y., Zhang, Q., & Xiao, X. (2023) · mBio · doi:10.1128/mbio.02032-23 · Cited by 180
Mechanisms of weight loss and improved metabolism following bariatric surgery
Mulla, C. M., Middelbeek, R. J. W., & Patti, M. (2017) · Annals of the New York Academy of Sciences · doi:10.1111/nyas.13409 · Cited by 161
Shin, A. C., Zheng, H., & Berthoud, H. (2009) · Physiology & Behavior · doi:10.1016/j.physbeh.2009.02.010 · Cited by 153
“This lower gut hormone has now been convincingly demonstrated to suppress food intake in humans and rodents [130, 131] and is thought to be important for decreased food intake after Roux-en-Y gastric bypass surgery [132,133].”
Meal-Induced Hormone Responses in a Rat Model of Roux-en-Y Gastric Bypass Surgery
Shin, A. C., Zheng, H., Townsend, R. L., Sigalet, D. L., & Berthoud, H. (2010) · Endocrinology · doi:10.1210/en.2009-1332 · Cited by 150
“fusion resulted in larger meals taken by RYGB patients (6).”
BackgroundBile acids and bariatric surgery
Albaugh, V. L., Banan, B., Ajouz, H., Abumrad, N. N., & Flynn, C. R. (2017) · Molecular Aspects of Medicine · doi:10.1016/j.mam.2017.04.001 · Cited by 148
“We (Isbell et al., 2010) and others (Kashyap et al., 2010; Laferr ere et al., 2007; le Roux et al., 2007; Morínigo et al., 2006a) have described large increases in postprandial GLP-1 immediately after RYGB that are sustained in the long-term (Bose et al., 2010; Morínigo et al., 2006a, 2006b; Vidal…”
BackgroundWeight Regain After Gastric Bypass: Influence of Gut Hormones
Santo, M. A., Riccioppo, D., Pajecki, D., Kawamoto, F., de Cleva, R., Antonangelo, L., Marçal, L., & Cecconello, I. (2016) · Obesity Surgery · doi:10.1007/s11695-015-1908-z · Cited by 145
“early after surgery and is mediated by gastrointestinal hormones [14], which influence hunger and energy balance by regulating the intake, storage, and energy expenditure”
BackgroundResultWharton, S., Kuk, J. L., Luszczynski, M., Kamran, E., & Christensen, R. A. G. (2019) · Clinical Obesity · doi:10.1111/cob.12323 · Cited by 144
“Surgeries that remove a portion of the stomach (eg, RNYGB and gastric sleeve) are associated with increase in glucagon-like peptide-1 (GLP-1) levels, which have been thought to in part contribute to sustained weight loss post-surgery.(15,16) Despite these well-known differences due to the type of bariatric surgery, fe…”
BackgroundSimonen, M., Dali-Youcef, N., Kaminska, D., Venesmaa, S., Käkelä, P., Pääkkönen, M., Hallikainen, M., Kolehmainen, M., Uusitupa, M., Moilanen, L., et al. (2012) · Obesity Surgery · doi:10.1007/s11695-012-0673-5 · Cited by 145
“The most common explanation for the more effective improvement in blood glucose levels after RYGB is altered secretion of gastrointestinal hormones, including GLP-1 and GIP, which stimulate insulin secretion [5–8].”
BackgroundNeff, K., Olbers, T., & le Roux, C. W. (2013) · BMC Medicine · doi:10.1186/1741-7015-11-8 · Cited by 150
Roles of the gut in the metabolic syndrome: an overview
Fändriks, L. (2016) · Journal of Internal Medicine · doi:10.1111/joim.12584 · Cited by 146
Olbers, T., Gronowitz, E., Werling, M., Marlid, S., Flodmark, C., Peltonen, M., Gothberg, G., Karlsson, J., Ekbom, K., Sjöström, L., et al. (2012) · International Journal of Obesity · doi:10.1038/ijo.2012.160 · Cited by 149
Penney, N. C., Kinross, J. K., Newton, R. C., & Purkayastha, S. (2015) · International Journal of Obesity · doi:10.1038/ijo.2015.115 · Cited by 146
Gut hormones: Implications for the treatment of obesity
Neary, M. T., & Batterham, R. L. (2009) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2009.06.005 · Cited by 140
Changes in neurohormonal gut peptides following bariatric surgery
Ochner, C. N., Gibson, C. D., Shanik, M. H., Goel, V., & Geliebter, A. (2010) · International Journal of Obesity · doi:10.1038/ijo.2010.132 · Cited by 137
Bose, M., Oliván, B., Teixeira, J., Pi-Sunyer, X., & Laferrère, B. (2008) · Obesity Surgery · doi:10.1007/s11695-008-9696-3 · Cited by 132
“The GLP-1 increase occurs as early as 2 days after GBP [71] and persists at 6 months and 1 year [72].”
BackgroundThe future role of gut hormones in the treatment of obesity
Troke, R., Tan, T., & Bloom, S. R. (2013) · Therapeutic Advances in Chronic Disease · doi:10.1177/2040622313506730 · Cited by 128
Longitudinal changes in pancreatic and adipocyte hormones following Roux-en-Y gastric bypass surgery
Swarbrick, M. M., Stanhope, K. L., Austrheim-Smith, I. T., Loan, M. D. V., Ali, M. R., Wolfe, B. M., & Havel, P. J. (2008) · Diabetologia · doi:10.1007/s00125-008-1118-5 · Cited by 127
“For example, postprandial GLP-1 levels increase as early as 2 days after RYGBP [26]; and in addition to its potential effects to stimulate insulin secretion, GLP-1 has actions to suppress endogenous glucose production, promote glucose uptake, and importantly, to reduce glucagon secretion [27].”
BackgroundThe role of gut hormone peptide YY in energy and glucose homeostasis: Twelve years on
Manning, S., & Batterham, R. L. (2014) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021113-170404 · Cited by 124
Alterations in Gut Hormones After Laparoscopic Sleeve Gastrectomy
Dimitriadis, E., Daskalakis, M., Kampa, M., Peppe, A., Papadakis, J. A., & Melissas, J. (2012) · Annals of Surgery · doi:10.1097/sla.0b013e31826e1846 · Cited by 122
Modulation of taste responsiveness and food preference by obesity and weight loss
Berthoud, H.-R., & Zheng, H. (2012) · Physiology & Behavior · doi:10.1016/j.physbeh.2012.04.004 · Cited by 123
“For example, circulating levels of both insulin and the lower gut hormone GLP-1 are affected by obesity [69], and both have been shown to modulate reward functions [70,71].”
GLP-1 physiology in obesity and development of incretin-based drugs for chronic weight management
Holst, J. J. (2024) · Nature Metabolism · doi:10.1038/s42255-024-01113-9 · Cited by 125
“During somatostatin infusion, there is also a significant increase in food intake, supporting the effects of the gut hormones 100,101 .”
Goldstone, A. P., Miras, A. D., Scholtz, S., Jackson, S., Neff, K. J., Pénicaud, L., Geoghegan, J., Chhina, N., Durighel, G., Bell, J. D., et al. (2016) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2015-2665 · Cited by 121
Phillips, L. K., & Prins, J. B. (2011) · Annals of the New York Academy of Sciences · doi:10.1111/j.1749-6632.2012.06491.x · Cited by 122
The Effect of Bariatric Surgery on Intestinal Absorption and Transit Time
Carswell, K. A., Vincent, R. P., Belgaumkar, A. P., Sherwood, R. A., Amiel, S. A., Patel, A. G., & le Roux, C. W. (2013) · Obesity Surgery · doi:10.1007/s11695-013-1166-x · Cited by 119
“Interestingly, these rises in post-prandial GLP-1 and PYY secretion have been shown to increase further over the first 6 months post-RYGB [61, 88].”
Background
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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