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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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“Alterations in satiety hormone levels do occur following bariatric surgery and have been implicated in the reduction in caloric intake and maintenance of lower body weights (24-31).”
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“Several studies have shown that the weight loss and improved glycemic control that are achieved following bariatric surgery are associated with the increased concentrations of incretins, including glucagon-like peptide-1 (GLP-1), glucagon, oxyntomodulin (OXM) and gastric inhibitory peptide (GIP).25-29 These findings s…”
BackgroundInfluentialWishing for Deburdening Through a Sustainable Control After Bariatric Surgery
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“This is supported by the observation that elevated fasting and postprandial GLP-1 secretion after bariatric surgery are associated with the magnitude of weight loss [152, 153].”
BackgroundChanges in the mucosa of the Roux‐limb after gastric bypass surgery
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“The reasons for this success are, however, debated, including a wide range of theoretical explanations.(2,3) The Roux-en-Y method markedly changes the order of gastrointestinal continuity.”
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“A recent study demonstrated a causality link between the exaggerated PYY and GLP-1 response and the enhanced satiety after RYGB [ 14 ].”
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“%) after gastric bypass exhibit a significant GLP-1 response, while those with poor weight loss outcomes have an attenuated GLP-1 response [186].”
BackgroundIs the Roux Limb a Determinant for Meal Size After Gastric Bypass Surgery?
Björklund, P., Laurenius, A., Een, E., Olbers, T., Lönroth, H., & Fändriks, L. (2010) · Obesity Surgery · doi:10.1007/s11695-010-0192-1 · Cited by 57
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“, 2007) ormild-obese (Lee et al., 2010) humans with T2D.”
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Effect of bypassing the proximal gut on gut hormones involved with glycemic control and weight loss
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Intestinal gluconeogenesis: key signal of central control of energy and glucose homeostasis
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Gastrointestinal function and eating behavior after gastric bypass and duodenal switch
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“Recent animal and human studies, however, have proposed a number of involved mechanisms, including a reduction in food intake and uptake of nutrients, attenuated appetite and increased satiety mediated through changes in gut hormone physiology, increased energy expenditure at rest, and altered food preference toward f…”
BackgroundWeight-Independent Mechanisms of Glucose Control After Roux-en-Y Gastric Bypass
Laferrère, B., & Pattou, F. N. (2018) · Frontiers in Endocrinology · doi:10.3389/fendo.2018.00530 · Cited by 60
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Physiological Mechanisms behind Roux-en-Y Gastric Bypass Surgery
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Gastrointestinal hormones, energy balance and bariatric surgery
Bueter, M., & le Roux, C. W. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.146 · Cited by 53
Adiposopathy and bariatric surgery: is ‘sick fat’ a surgical disease?
Bays, H. E., Laferrère, B., Dixon, J. B., Aronne, L. J., González-Campoy, J. M., Apovian, C. M., Wolfe, B. M., & The adiposopathy and bariatric surgery working group (2009) · International Journal of Clinical Practice · doi:10.1111/j.1742-1241.2009.02151.x · Cited by 53
The Hundred Most Cited Articles in Bariatric Surgery
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“A study by le Roux [17] reported an increase in GLP-1 and PYY as early as 2 days after surgery and before significant weight loss.”
MethodInfluentialThe physiology of altered eating behaviour after Roux‐en‐Y gastric bypass
le Roux, C. W., & Bueter, M. (2014) · Experimental Physiology · doi:10.1113/expphysiol.2014.078378 · Cited by 52
After bariatric surgery, what vitamins should be measured and what supplements should be given?
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Fenske, W. K., Bueter, M., Miras, A. D., Ghatei, M. A., Bloom, S. R., & le Roux, C. W. (2011) · International Journal of Obesity · doi:10.1038/ijo.2011.126 · Cited by 52
The satiety hormone peptide YY as a regulator of appetite
Vincent, R. P., & le Roux, C. W. (2008) · Journal of Clinical Pathology · doi:10.1136/jcp.2007.048488 · Cited by 52
Mechanisms to Elevate Endogenous GLP-1 Beyond Injectable GLP-1 Analogs and Metabolic Surgery
Briere, D. A., Bueno, A. B., Gunn, E. J., Michael, M. D., & Sloop, K. W. (2017) · Diabetes · doi:10.2337/db17-0607 · Cited by 51
“Patients with extreme weight loss following metabolic surgery have been treated with the somatostatin analog octreotide, which results in dramatically reduced surgery-induced elevation of GLP-1, as well as a return of appetite and increased food intake (44,45), suggesting a dominant role of somatostatin in suppressing…”
BackgroundPotential gut–brain mechanisms behind adverse mental health outcomes of bariatric surgery
Brown, R. M., Guerrero-Hreins, E., Brown, W. A., le Roux, C. W., & Sumithran, P. (2021) · Nature Reviews Endocrinology · doi:10.1038/s41574-021-00520-2 · Cited by 49
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“Our findings are consistent with evidence from bariatric surgery studies, reporting that poorer long-term weight-loss maintenance outcomes are associated with attenuated GLP-1 response [36].”
ResultRoux-en-Y Gastric Bypass Operation in Rats
Bueter, M., Abegg, K., Seyfried, F., Lutz, T. A., & le Roux, C. W. (2012) · Journal of Visualized Experiments · doi:10.3791/3940 · Cited by 50
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“Higher postoperative levels of physical activity [8] and changes in food preferences may also predict WL [9, 10], and enhanced postprandial secretion of gut hormones following surgery are known to play an important role in the postoperative WL [11, 12].”
BackgroundInfluentialImproved glucose metabolism after gastric bypass: evolution of the paradigm
Pournaras, D. J., Nygren, J., Hagström-Toft, E., Arner, P., le Roux, C. W., & Thorell, A. (2016) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2016.03.020 · Cited by 48
“Other factors implicated in mediating the effect of the bypass of the gut, such as gut hormones, bile acids, microbiota, and meal-associated energy expenditure, may also be responsible for the superior postprandial glycemia after RYGB [26–28].”
BackgroundBariatric surgery and diabetes remission: Who would have thought it?
Singh, A., Singh, R., & Kota, S. (2015) · Indian Journal of Endocrinology and Metabolism · doi:10.4103/2230-8210.163113 · Cited by 48
“After malabsorptive surgeries, there is postprandial increase in PYY in the earliest postsurgical period even before weight loss occurs.[75,76]”
BackgroundTam, C. S., Berthoud, H., Bueter, M., Chakravarthy, M. V., Geliebter, A., Hajnal, A. S., Holst, J. J., Kaplan, L. M., Pories, W. J., Raybould, H. E., et al. (2011) · Obesity Reviews · doi:10.1111/j.1467-789x.2011.00902.x · Cited by 47
“For instance, although GLP-1 and PYY levels are raised postprandially in both humans and rats, fasting levels are not increased in humans (31,32).”
BackgroundNguyen, K. T., & Körner, J. (2014) · Current Diabetes Reports · doi:10.1007/s11892-014-0481-5 · Cited by 48
The Use of Rat and Mouse Models in Bariatric Surgery Experiments
Lutz, T. A., & Bueter, M. (2016) · Frontiers in Nutrition · doi:10.3389/fnut.2016.00025 · Cited by 52
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“were the first to show that a significant increase in postprandial GLP-1 response occurs only 2 days after RYGB in 16 normo-glycaemic patients [54].”
BackgroundGastrointestinal hormones and weight loss response after Roux-en-Y gastric bypass
de Hollanda, A., Jiménez, A., Corcelles, R., Lacy, A. M., Patrascioiu, I., & Vidal, J. (2014) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2014.01.022 · Cited by 47
“Several gastrointestinal modifications have been proposed as mediators of weight loss and weight loss maintenance after Roux-en-Y Gastric Bypass (RYGB), the most commonly performed BS technique [7–10].”
BackgroundMethodResultInfluentialThe effect of bariatric surgery on gut hormones that alter appetite
Pournaras, D. J., & le Roux, C. W. (2009) · Diabetes & Metabolism · doi:10.1016/s1262-3636(09)73457-3 · Cited by 49
“Lower PYY and GLP-1 postprandial responses were associated with inferior weight loss [15].”
BackgroundMethodResultInfluentialGut microbiota and therapy for obesity and type 2 diabetes
Zhang, L., Wang, P., Huang, J., Xing, Y., Wong, F. S., Suo, J., & Li, W. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1333778 · Cited by 56
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The endogenous preproglucagon system is not essential for gut growth homeostasis in mice
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“Some authors have suggested that duodenum bypass contributes to a decrease in an anti-incretin substance that normally would oppose the K cell-derived GIP, while others have suggested that the lower gut and the increased GLP-1 secretion from the L cells play an important role [69, 81, 82].”
BackgroundResultIs there a place for incretin therapies in obesity and prediabetes?
Holst, J. J., & Deacon, C. F. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.01.004 · Cited by 44
Relationship between gut hormones and glucose homeostasis after bariatric surgery
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“Combination therapy with amylin and peptide YY[3-36] in obese rodents: anorexigenic synergy and weight loss additivity.”
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Are Bile Acids the New Gut Hormones? Lessons From Weight Loss Surgery Models
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“Roux-en-Y gastric bypass (RYGB) is one of the most efficient surgical methods, but for unknown reasons, the success of weight loss varies among RYGB patients, and some patients fail to achieve substantial weight loss (le Roux et al., 2007).”
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Lessons Learned from Gastric Bypass Operations in Rats
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New Targets for Drug Treatment of Obesity
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Effects of glucagon like peptide-1 to mediate glycemic effects of weight loss surgery
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“Increases in post-prandial GLP-1 levels have also been implicated in the observed weight loss following bariatric surgery (1,4).”
BackgroundInfluentialGut hormone release after gastric bypass depends on the length of the biliopancreatic limb
Patrício, B. G., Morais, T., Guimarães, M., Veedfald, S., Hartmann, B., Hilsted, L., Holst, J. J., Nora, M. C., & Monteiro, M. P. (2018) · International Journal of Obesity · doi:10.1038/s41366-018-0117-y · Cited by 40
Metabolic and Bariatric Surgery for Obesity
Vidal, J., Corcelles, R., Jiménez, A., Flores, L., & Lacy, A. M. (2017) · Gastroenterology · doi:10.1053/j.gastro.2017.01.051 · Cited by 43
The PYY/Y2R-Deficient Mouse Responds Normally to High-Fat Diet and Gastric Bypass Surgery
Boland, B. B., Mumphrey, M. B., Zheng, H., Gill, B. M., Townsend, R. L., Yu, S., Münzberg, H., Morrison, C. D., Trevaskis, J. L., & Berthoud, H. (2019) · Nutrients · doi:10.3390/nu11030585 · Cited by 39
“Altered secretion and circulating levels of key gut hormones have been proposed as one of the major mechanisms driving metabolic disease resolution following RYGB and other bariatric surgeries [9,10].”
BackgroundInfluentialMumphrey, M. B., Hao, Z., Townsend, R. L., Patterson, L. M., Münzberg, H., Morrison, C. D., Ye, J., & Berthoud, H. R. (2016) · International Journal of Obesity · doi:10.1038/ijo.2016.38 · Cited by 37
Mazidi, M., Caravatto, P. P. D. P., Speakman, J. R., & COHEN, R. V. (2017) · Obesity Surgery · doi:10.1007/s11695-017-2549-1 · Cited by 40
van den Broek, M., de Heide, L. J. M., Sips, F. L. P., Koehorst, M., van Zutphen, T., Emous, M., van Faassen, M. H. J. R., Groen, A. K., van Riel, N. A. W., de Boer, J. F., et al. (2021) · International Journal of Obesity · doi:10.1038/s41366-020-00726-w · Cited by 38
“An exaggerated postprandial GLP-1 response and altered β-cell function have been suggested as contributing factors [11, 12] but a clear pathophysiological mechanism has not been elucidated.”
To Band or Not to Band—Early Results of Banded Sleeve Gastrectomy
Karcz, W. K., Karcz-Socha, I., Marjanović, G., Kuesters, S., Goos, M., Hopt, U. T., Szewczyk, T., Baumann, T., & Grueneberger, J. M. (2014) · Obesity Surgery · doi:10.1007/s11695-014-1189-y · Cited by 38
“When drawing a parallel to BRYGB, it has to be noted that additional rerouting of the intestine is known to substantially influence appetite, which might effect pouch dilatation, as smaller meals are consumed [19].”
BackgroundCaruana, J. A., Monte, S. V., Jacobs, D. M., Voytovich, C., Ghanim, H., & Dandona, P. (2015) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2015.08.001 · Cited by 37
“[17] have reported on a small group of 7 patients that the response of these hormones to RYGB is attenuated in poor versus successful WL responders.”
BackgroundTREM2 macrophages mediate the beneficial effects of bariatric surgery against MASH
Fredrickson, G., Florczak, K. L., Barrow, F., Mahmud, S., DIETSCHE, K. B., Wang, H., Parthiban, P., Hakeem, A. N., Almutlaq, R. N., Adeyi, O. A., et al. (2024) · Hepatology · doi:10.1097/hep.0000000000001098 · Cited by 38
“[6] Several mechanisms of weight-loss – independent improvements in metabolism due to bariatric surgery have been proposed in mice and humans, including gut hormones, [7] intestinal tissue reprogramming, [8] changes in the gut microbiome, [9] and iron absorption.”
Chelikani, P. K., Shah, I. H., Taqi, E., Sigalet, D. L., & Koopmans, H. H. (2010) · Obesity Surgery · doi:10.1007/s11695-010-0139-6 · Cited by 37
Effects of Gastrogastric Fistula Repair on Weight Loss and Gut Hormone Levels
O’Brien, C. S., Wang, G., McGinty, J., Agenor, K., Dutia, R., Colarusso, A., Park, K., Koshy, N., & Laferrère, B. (2013) · Obesity Surgery · doi:10.1007/s11695-013-0917-z · Cited by 37
Laurenius, A., Werling, M., le Roux, C. W., Fändriks, L., & Olbers, T. (2014) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2014.04.007 · Cited by 36
“The mechanisms of action of LRYGB include increased postprandial gut hormones, increased satiety [8,9], reduced hunger [10], and alterations in food preference [11].”
BackgroundJensen, C. Z., Bojsen-Møller, K. N., Svane, M. S., Holst, L. M., Hermansen, K., Hartmann, B., Albrechtsen, N. J. W., Kuhre, R. E., Kristiansen, V. B., Rehfeld, J. F., et al. (2020) · American Journal of Physiology-Gastrointestinal and Liver Physiology · doi:10.1152/ajpgi.00265.2019 · Cited by 37
Gu, L., Lin, K., Du, N., Ng, D. M., Lou, D., & Chen, P. (2020) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2020.10.018 · Cited by 37
Bryant, E. J., King, N. A., Falkén, Y., Hellström, P. M., Holst, J. J., Blundell, J. E., & Näslund, E. B. (2012) · Surgery for Obesity and Related Diseases · doi:10.1016/j.soard.2012.09.011 · Cited by 37
“Roux-en-Y gastric bypass (RYGB) alters levels of circulating appetite peptides 4 , 5 , but the association of such physiological changes with the subsequent expression of motivations to eat and eating behaviour traits is less well known.”
Glucagon‐Like Peptide‐1: Actions and Influence on Pancreatic Hormone Function
Davis, E., & Sandoval, D. A. (2020) · Comprehensive physiology · doi:10.1002/cphy.c190025 · Cited by 53
Bowels control brain: gut hormones and obesity
Bewick, G. A. (2012) · Biochemia Medica · doi:10.11613/bm.2012.032 · Cited by 36
Matzko, M. E., Argyropoulos, G. A., Wood, G. C., Chu, X., McCarter, R., Still, C. D., & Gerhard, G. S. (2012) · Obesity Surgery · doi:10.1007/s11695-012-0631-2 · Cited by 36
The Role of Hormonal Factors in Weight Loss and Recidivism after Bariatric Surgery
Pedersen, S. D. (2013) · Gastroenterology Research and Practice · doi:10.1155/2013/528450 · Cited by 35
Bariatric surgery to unload the stressed heart: a metabolic hypothesis
Algahim, M. F., Sen, S., & Taegtmeyer, H. (2012) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00626.2011 · Cited by 36
“Although several studies have shown a paradoxical increase in satiety promoting gut hormones such as glucagon-like peptide 1 (GLP-1) and peptide YY (5, 44), particularly after Roux-en-Y gastric bypass surgery, this satiety feeling appears transient, as patients do not reach ideal body weight and many regain weight in…”
BackgroundCracking the combination: Gut hormones for the treatment of obesity and diabetes
Alexiadou, K., Anyiam, O., & Tan, T. (2019) · Journal of Neuroendocrinology · doi:10.1111/jne.12664 · Cited by 34
Physiology of Weight Loss Surgery
Park, C. W., & Torquati, A. (2011) · Surgical Clinics of North America · doi:10.1016/j.suc.2011.08.009 · Cited by 37
Moving beyond energy homeostasis: New roles for glucagon-like peptide-1 in food and drug reward
Reddy, I. A., Stanwood, G. D., & Galli, A. (2013) · Neurochemistry International · doi:10.1016/j.neuint.2013.10.003 · Cited by 36
“In support of this notion, RYGB ‘‘good responders’’ ( 40% weight loss) secreted significantly more GLP-1 in response to a post-operative test meal than ‘‘poor responders’’ (<20% weight loss) (le Roux et al., 2007; Moran and Dailey, 2011).”
Mechanisms of Weight Loss after Gastric Bypass and Gastric Banding
Bueter, M., Ashrafian, H., & le Roux, C. W. (2009) · Obesity Facts · doi:10.1159/000232383 · Cited by 35
Metabolic surgery—principles and current concepts
Gass, M., Beglinger, C., & Peterli, R. (2011) · Langenbeck s Archives of Surgery · doi:10.1007/s00423-011-0834-3 · Cited by 34
Gastrointestinal hormones and their role in obesity
Choudhury, S., Tan, T., & Bloom, S. R. (2015) · Current Opinion in Endocrinology Diabetes and Obesity · doi:10.1097/med.0000000000000216 · Cited by 35
Bariatric Surgery and the Central Nervous System
Rao, R. S. (2012) · Obesity Surgery · doi:10.1007/s11695-012-0649-5 · Cited by 35
“Inhibition of PYY and GLP-1 secretion by octreotide also resulted in increased food intake in human patients after RYGB [28].”
BackgroundPostprandial Insulin Secretion After Gastric Bypass Surgery
Holst, J. J. (2011) · Diabetes · doi:10.2337/db11-0798 · Cited by 35
“5–2 m more distal to the duodenum clearly poses a dramatic exposure of nutrients to the mucosa there, and this is clearly reflected in a grossly exaggerated secretion of gut hormones (4,5).”
Consequences of bariatric surgery on oesophageal function in health and disease
Naik, R. D., Choksi, Y. A., & Vaezi, M. F. (2015) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/nrgastro.2015.202 · Cited by 36
Brzozowska, M. M., Isaacs, M., Bliuc, D., Baldock, P. A. J., Eisman, J. A., White, C., & Greenfield, J. R. (2023) · Scientific Reports · doi:10.1038/s41598-023-33317-6 · Cited by 38
Abegg, K., Schiesser, M., Lutz, T. A., & Bueter, M. (2013) · Physiology & Behavior · doi:10.1016/j.physbeh.2013.03.027 · Cited by 34
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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