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Marin RC, Radu AF, Negru PA, Radu A, Negru D, Aron RAC, Bodog TM, Bodog RF, Maghiar PB, Brata R. Integrated Insights into Metabolic and Bariatric Surgery: Improving Life Quality and Reducing Mortality in Obesity. MEDICINA (KAUNAS, LITHUANIA) 2024; 61:14. [PMID: 39858996 PMCID: PMC11767230 DOI: 10.3390/medicina61010014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/17/2024] [Revised: 12/11/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025]
Abstract
Metabolic and bariatric surgery (MBS) is an effective intervention for patients with severe obesity and metabolic comorbidities, particularly when non-surgical weight loss methods prove insufficient. MBS has shown significant potential for improving quality of life and metabolic health outcomes in individuals with obesity, yet it carries inherent risks. Although these procedures offer a multifaceted approach to obesity treatment and its clinical advantages are well-documented, the limited understanding of its long-term outcomes and the role of multidisciplinary care pose challenges. With an emphasis on quality-of-life enhancements and the handling of postoperative difficulties, the present narrative review seeks to compile the most recent findings on MBS while emphasizing the value of an integrated approach to maximize patient outcomes. Effective MBS and patients' management require a collaborative team approach, involving surgeons, dietitians, psychologists, pharmacists, and other healthcare providers to address not only physiological but also psychosocial patient needs. Comparative studies demonstrate the efficacy of various MBS methods, including Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy that may considerably decrease morbidity and mortality in individuals with obesity. Future studies should target long-term patient treatment, and decision making should be aided by knowledge of obesity, comorbidity recurrence rates, and permanence of benefits.
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Affiliation(s)
- Ruxandra-Cristina Marin
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania; (R.-C.M.); (A.R.); (D.N.); (T.M.B.); (R.F.B.)
| | - Andrei-Flavius Radu
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania; (R.-C.M.); (A.R.); (D.N.); (T.M.B.); (R.F.B.)
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania;
| | - Paul Andrei Negru
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania; (R.-C.M.); (A.R.); (D.N.); (T.M.B.); (R.F.B.)
| | - Ada Radu
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania; (R.-C.M.); (A.R.); (D.N.); (T.M.B.); (R.F.B.)
- Department of Pharmacy, Faculty of Medicine and Pharmacy, University of Oradea, 410028 Oradea, Romania
| | - Denisa Negru
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania; (R.-C.M.); (A.R.); (D.N.); (T.M.B.); (R.F.B.)
| | - Raluca Anca Corb Aron
- Department of Preclinical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania;
| | - Teodora Maria Bodog
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania; (R.-C.M.); (A.R.); (D.N.); (T.M.B.); (R.F.B.)
| | - Ruxandra Florina Bodog
- Doctoral School of Biological and Biomedical Sciences, University of Oradea, 410087 Oradea, Romania; (R.-C.M.); (A.R.); (D.N.); (T.M.B.); (R.F.B.)
| | - Paula Bianca Maghiar
- Department of Surgical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania;
| | - Roxana Brata
- Department of Medical Disciplines, Faculty of Medicine and Pharmacy, University of Oradea, 410073 Oradea, Romania;
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Albaugh VL, He Y, Münzberg H, Morrison CD, Yu S, Berthoud HR. Regulation of body weight: Lessons learned from bariatric surgery. Mol Metab 2023; 68:101517. [PMID: 35644477 PMCID: PMC9938317 DOI: 10.1016/j.molmet.2022.101517] [Citation(s) in RCA: 38] [Impact Index Per Article: 19.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2021] [Revised: 05/04/2022] [Accepted: 05/21/2022] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Bariatric or weight loss surgery is currently the most effective treatment for obesity and metabolic disease. Unlike dieting and pharmacology, its beneficial effects are sustained over decades in most patients, and mortality is among the lowest for major surgery. Because there are not nearly enough surgeons to implement bariatric surgery on a global scale, intensive research efforts have begun to identify its mechanisms of action on a molecular level in order to replace surgery with targeted behavioral or pharmacological treatments. To date, however, there is no consensus as to the critical mechanisms involved. SCOPE OF REVIEW The purpose of this non-systematic review is to evaluate the existing evidence for specific molecular and inter-organ signaling pathways that play major roles in bariatric surgery-induced weight loss and metabolic benefits, with a focus on Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), in both humans and rodents. MAJOR CONCLUSIONS Gut-brain communication and its brain targets of food intake control and energy balance regulation are complex and redundant. Although the relatively young science of bariatric surgery has generated a number of hypotheses, no clear and unique mechanism has yet emerged. It seems increasingly likely that the broad physiological and behavioral effects produced by bariatric surgery do not involve a single mechanism, but rather multiple signaling pathways. Besides a need to improve and better validate surgeries in animals, advanced techniques, including inducible, tissue-specific knockout models, and the use of humanized physiological traits will be necessary. State-of-the-art genetically-guided neural identification techniques should be used to more selectively manipulate function-specific pathways.
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Affiliation(s)
- Vance L Albaugh
- Translational and Integrative Gastrointestinal and Endocrine Research Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Yanlin He
- Brain Glycemic and Metabolism Control Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Heike Münzberg
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Christopher D Morrison
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Sangho Yu
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA
| | - Hans-Rudolf Berthoud
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA, USA.
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Franquet E, Watts G, Kolodny GM, Goldfine AB, Patti ME. PET-CT reveals increased intestinal glucose uptake after gastric surgery. Surg Obes Relat Dis 2019; 15:643-649. [PMID: 30773442 DOI: 10.1016/j.soard.2019.01.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2018] [Revised: 01/16/2019] [Accepted: 01/18/2019] [Indexed: 12/18/2022]
Abstract
BACKGROUND Mechanisms of metabolic improvement after bariatric surgery remain incompletely understood. Intestinal glucose uptake is increased after gastric bypass in rodents, potentially contributing to reduced blood glucose and type 2 diabetes remission. OBJECTIVE We assessed whether intestinal glucose uptake is increased in humans after gastric surgery. SETTING University Hospital, United States. METHODS In a retrospective, case-control cohort study, positron emission tomography-computerized tomography scans performed for clinical indications were analyzed to quantify intestinal glucose uptake in patients with or without history of gastric surgery. We identified 19 cases, defined as patients over age 18 with prior gastric surgery (Roux-en-Y gastric bypass [n = 10], sleeve gastrectomy [n = 1], or Billroth I [n = 2] or II gastrectomy [n = 6]), and 43 controls without gastric surgery, matched for age, sex, and indication for positron emission tomography-computerized tomography. Individuals with gastrointestinal malignancy or metformin treatment were excluded. Images were obtained 60 minutes after 18F-fluorodeoxyglucose injection (4.2 MBq/kg), and corrected by attenuation; noncontrast low-dose computerized tomography was obtained in parallel. Fused and nonfused images were analyzed; standardized uptake values were calculated for each region by volumes of interest at the region of highest activity. RESULTS Both standardized uptake values maximum and mean were significantly increased by 41% to 98% in jejunum, ascending, and transverse colon in patients with prior gastric surgery (P < .05 versus controls). CONCLUSION Intestinal glucose uptake is increased in patients with prior gastric surgery. Prospective studies are important to dissect the contributions of weight loss, dietary factors, and systemic metabolism, and to determine the relationship with increased insulin-independent glucose uptake and reductions in glycemia.
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Affiliation(s)
- Elisa Franquet
- Division of Nuclear Medicine, Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - George Watts
- Division of Nuclear Medicine, Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Gerald M Kolodny
- Division of Nuclear Medicine, Department of Radiology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts
| | - Allison B Goldfine
- Research Division, Joslin Diabetes Center, and Harvard Medical School, Boston, Massachusetts
| | - Mary-Elizabeth Patti
- Research Division, Joslin Diabetes Center, and Harvard Medical School, Boston, Massachusetts.
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Cazzo E, Pareja JC, Chaim EA, Coy CSR, Magro DO. Glucagon-Like Peptides 1 and 2 Are Involved in Satiety Modulation After Modified Biliopancreatic Diversion: Results of a Pilot Study. Obes Surg 2018; 28:506-512. [PMID: 28808865 DOI: 10.1007/s11695-017-2875-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
BACKGROUND This paper aimed to evaluate the influence of modified biliopancreatic diversion (BPD) on the levels of GLP-1 and GLP-2 and correlate them with satiety regulation. METHODS This is a pilot prospective cohort study that evaluated six mildly obese individuals with type 2 diabetes mellitus, which underwent modified BPD and were followed-up for 12 months. Levels of GLP-1 and GLP-2 after a standard meal tolerance test were determined and correlated with satiety scores obtained by means of a visual analogue scale (VAS). RESULTS There were significant changes in BMI (33 ± 2.2 versus 26.3 ± 2.2 kg/m2; p < 0.001), HbA1c (7.9 ± 1.6 versus 5.8 ± 1.2%; p = 0.026), total cholesterol (172.3 ± 11.1 versus 134.7 ± 16.1 mg/dL; p < 0.001), LDL-c (103.3 ± 13 versus 64.6 ± 12.2 mg/dL; p < 0.001), and postprandial GLP-2 (972.7 ± 326.2 versus 1993.2 ± 1024.7; p = 0. 044). None of the scores obtained in the VAS significantly changed after surgery. After surgery, there were significant correlations of VAS scores and GLP-1 levels in question 01 ("how hungry do you feel?"; R = -0.928; p = .008) and GLP-2 levels in questions 02 ("how full do you feel?" R = 0.943; p = 0.005) and 04 ("how much do you think you can eat now? R = -0.829; p = 0.042). CONCLUSIONS Modified BPD does not lead to significant changes in satiety evaluated by the VAS; different aspects of satiety regulation are correlated with the postprandial levels of GLP-1 (hunger feeling) and GLP-2 (satiation feeling and desire to eat) 1 year after modified BPD, signaling a specific postoperative gut hormone-related modulation of appetite.
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Affiliation(s)
- Everton Cazzo
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n, Cidade Universitaria Zeferino Vaz, CEP, Campinas, SP, 13085-000, Brazil.
| | - José Carlos Pareja
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n, Cidade Universitaria Zeferino Vaz, CEP, Campinas, SP, 13085-000, Brazil
| | - Elinton Adami Chaim
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n, Cidade Universitaria Zeferino Vaz, CEP, Campinas, SP, 13085-000, Brazil
| | - Cláudio Saddy Rodrigues Coy
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n, Cidade Universitaria Zeferino Vaz, CEP, Campinas, SP, 13085-000, Brazil
| | - Daniéla Oliveira Magro
- Department of Surgery, Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n, Cidade Universitaria Zeferino Vaz, CEP, Campinas, SP, 13085-000, Brazil
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GLP-2 receptor signaling controls circulating bile acid levels but not glucose homeostasis in Gcgr -/- mice and is dispensable for the metabolic benefits ensuing after vertical sleeve gastrectomy. Mol Metab 2018; 16:45-54. [PMID: 29937214 PMCID: PMC6157461 DOI: 10.1016/j.molmet.2018.06.006] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2018] [Revised: 06/04/2018] [Accepted: 06/06/2018] [Indexed: 02/06/2023] Open
Abstract
Objective Therapeutic interventions that improve glucose homeostasis such as attenuation of glucagon receptor (Gcgr) signaling and bariatric surgery share common metabolic features conserved in mice and humans. These include increased circulating levels of bile acids (BA) and the proglucagon-derived peptides (PGDPs), GLP-1 and GLP-2. Whether BA acting through TGR5 (Gpbar1) increases PGDP levels in these scenarios has not been examined. Furthermore, although the importance of GLP-1 action has been interrogated in Gcgr−/− mice and after bariatric surgery, whether GLP-2 contributes to the metabolic benefits of these interventions is not known. Methods To assess whether BA acting through Gpbar1 mediates improved glucose homeostasis in Gcgr−/− mice we generated and characterized Gcgr−/−:Gpbar1−/− mice. The contribution of GLP-2 receptor (GLP-2R) signaling to intestinal and metabolic adaptation arising following loss of the Gcgr was studied in Gcgr−/−:Glp2r−/− mice. The role of the GLP-2R in the metabolic improvements evident after bariatric surgery was studied in high fat-fed Glp2r−/− mice subjected to vertical sleeve gastrectomy (VSG). Results Circulating levels of BA were markedly elevated yet similar in Gcgr−/−:Gpbar1+/+ vs. Gcgr−/−:Gpbar1−/− mice. Loss of GLP-2R lowered levels of BA in Gcgr−/− mice. Gcgr−/−:Glp2r−/− mice also exhibited shifts in the proportion of circulating BA species. Loss of Gpbar1 did not impact body weight, intestinal mass, or glucose homeostasis in Gcgr−/− mice. In contrast, small bowel growth was attenuated in Gcgr−/−:Glp2r−/− mice. The improvement in glucose tolerance, elevated circulating levels of GLP-1, and glucose-stimulated insulin levels were not different in Gcgr−/−:Glp2r+/+ vs. Gcgr−/−:Glp2r−/− mice. Similarly, loss of the GLP-2R did not attenuate the extent of weight loss and improvement in glucose control after VSG. Conclusions These findings reveal that GLP-2R controls BA levels and relative proportions of BA species in Gcgr−/− mice. Nevertheless, the GLP-2R is not essential for i) control of body weight or glucose homeostasis in Gcgr−/− mice or ii) metabolic improvements arising after VSG in high fat-fed mice. Furthermore, despite elevations of circulating levels of BA, Gpbar1 does not mediate elevated levels of PGDPs or major metabolic phenotypes in Gcgr−/− mice. Collectively these findings refine our understanding of the relationship between Gpbar1, elevated levels of BA, PGDPs, and the GLP-2R in amelioration of metabolic derangements arising following loss of Gcgr signaling or after vertical sleeve gastrectomy.
GLP-2 receptor controls bile acid levels in Gcgr−/− mice. Gpbar1 is not required for the metabolic benefits or elevated levels of PGDPs in Gcgr−/− mice. GLP-2 regulates gut adaptation in Gcgr−/− mice. Bile acid profiles are altered in Gcgr−/− mice following loss of GLP-2R. GLP-2R is not required for improvements in glucose homeostasis or weight loss after VSG in mice.
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Werling M, Fändriks L, Olbers T, Mala T, Kristinsson J, Stenlöf K, Wallenius V, Docherty NG, le Roux CW. Biliopancreatic Diversion is associated with greater increases in energy expenditure than Roux-en-Y Gastric Bypass. PLoS One 2018; 13:e0194538. [PMID: 29617391 PMCID: PMC5884508 DOI: 10.1371/journal.pone.0194538] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2017] [Accepted: 03/05/2018] [Indexed: 01/14/2023] Open
Abstract
Objective The greater weight loss achieved following Biliopancreatic Diversion with Duodenal Switch (BPDS) versus Roux-en-Y Gastric Bypass (RYGB) has been attributed to the malabsorptive effects of BPDS. Increased weight loss after BPDS could also be underpinned by larger increases in energy expenditure. Hypothetically, the more radical reconfiguration of the small intestine in BPDS could result in an accentuated increase in meal associated thermogenesis (MAT). Design Female subjects (baseline mean age 40 years, mean BMI-55kg/m2) were assessed four years after randomization to BPDS (n = 6) or RYGB (n = 6). Energy expenditure (EE) and respiratory quotient (RQ) were measured by indirect calorimetry over 24 hours. A detailed protocol allowed for discrimination of basal metabolic rate (BMR), fasting EE and MAT as components of total energy expenditure (TEE) normalised for total and lean tissue by dual-energy x-ray absorptiometry. Results Median weight loss at follow-up was 1.5-fold higher following BPDS relative to RYGB, resulting in respective median BMIs of 29.5 kg/m2 (21.7 to 36.7) after BPDS and 37.8 kg/m2 (34.1 to 45.7) after RYGB (p = 0.015). The BPDS group had a lower fat:lean ratio compared to the RYGB group (p = 0.009). Overall 24-hour TEE adjusted for total tissue was higher in the BPDS group, as were BMR, fasting EE and MAT (all p<0.05). Differences between RYGB and BPDS in BMR and TEE were nullified when normalised for lean mass. Postprandial RQ increased significantly but to a similar extent in both groups. Conclusion Enhanced and prolonged MAT and lower fat:lean mass ratios after BPDS may explain relative increases in total energy expenditure as compared to RYGB.
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Affiliation(s)
- Malin Werling
- Department of Gastrosurgical Research and Education, Sahlgrenska academy, University of Gothenburg, Department of Surgery, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden
| | - Lars Fändriks
- Department of Gastrosurgical Research and Education, Sahlgrenska academy, University of Gothenburg, Department of Surgery, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden
| | - Torsten Olbers
- Department of Gastrosurgical Research and Education, Sahlgrenska academy, University of Gothenburg, Department of Surgery, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden
| | - Tom Mala
- Department of Morbid Obesity and Bariatric Surgery and Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway
| | - Jon Kristinsson
- Department of Morbid Obesity and Bariatric Surgery and Department of Gastrointestinal Surgery, Oslo University Hospital, Oslo, Norway
| | - Kaj Stenlöf
- Gothia Forum, Sahlgrenska University Hospital, Gothenburg, Sweden
| | - Ville Wallenius
- Department of Gastrosurgical Research and Education, Sahlgrenska academy, University of Gothenburg, Department of Surgery, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden
| | - Neil G. Docherty
- Department of Gastrosurgical Research and Education, Sahlgrenska academy, University of Gothenburg, Department of Surgery, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland
- * E-mail:
| | - Carel W. le Roux
- Department of Gastrosurgical Research and Education, Sahlgrenska academy, University of Gothenburg, Department of Surgery, Sahlgrenska University Hospital/Sahlgrenska, Gothenburg, Sweden
- Diabetes Complications Research Centre, Conway Institute, University College Dublin, Dublin, Ireland
- Investigative Science, Imperial College London, London, United Kingdom
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Cazzo E, Pareja JC, Geloneze B, Chaim EA, Barreto MRL, Magro DO. Postprandial GLP-2 Levels Are Increased After Biliopancreatic Diversion in Diabetic Individuals with Class I Obesity: a Prospective Study. Obes Surg 2018; 27:1809-1814. [PMID: 28101843 DOI: 10.1007/s11695-017-2554-4] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Biliopancreatic diversion (BPD) is a predominantly malabsorptive procedure. Glucagon-like peptide 2 (GLP-2) plays predominantly trophic effects on the gut. A significant increase in GLP-2 after BPD in rats was previously observed, but there are no studies investigating the effect of BPD in GLP-2 levels in humans. OBJECTIVE The aim of this study is to evaluate the influence of BPD on the release of GLP-2. METHODS This is a prospective cohort study that evaluated diabetic individuals with class I obesity which underwent BPD (Scopinaro operation) and were followed up for 12 months. Of 12 individuals, four did not comply with the proposed follow-up and were excluded from the analysis. GLP-2 levels were determined by means of an enzyme-linked immunosorbent assay (ELISA), and we collected serial lab samples through a standard meal tolerance test (MTT) in the immediate preoperative period and 12 months after surgery. RESULTS During standard MTT, we observed significant increases of GLP-2 levels from 15 to 60 min (respectively, at 15 min, 5.7 ± 3.4 versus 12.4 ± 4.3, p = 0.029; 30 min, 6 ± 3.5 versus 14.6 ± 3.9; p = 0.004; 45 min, 5.6 ± 4.1 versus 12.6 ± 5.2, p = 0.013; 60 min, 5.8 ± 2.9 versus 10.6 ± 5.6, p = 0.022); then it began to gradually decrease to levels close to the basal. DISCUSSION Our findings have confirmed that there is a significant increase in GLP-2 levels after BPD in humans. GLP-2 plays a number of roles which may be adaptive, compensatory, and beneficial in the context of BPD. The clinical implications of this finding remain to be completely understood.
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Affiliation(s)
- Everton Cazzo
- Department of Surgery; Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil.
| | - José Carlos Pareja
- Department of Surgery; Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Bruno Geloneze
- Research Laboratory of Metabolism and Diabetes (LIMED), Gastrocentro, State University of Campinas (UNICAMP), Campinas, SP, Brazil
| | - Elinton Adami Chaim
- Department of Surgery; Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Maria Rita Lazzarini Barreto
- Department of Surgery; Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
| | - Daniéla Oliveira Magro
- Department of Surgery; Faculty of Medical Sciences, State University of Campinas (UNICAMP), R. Alexander Fleming, s/n; Cidade Universitaria Zeferino Vaz, Campinas, SP, CEP 13085-000, Brazil
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Cazzo E, Gestic MA, Utrini MP, Chaim FDM, Geloneze B, Pareja JC, Chaim EA, Magro DO. GLP-2: A POORLY UNDERSTOOD MEDIATOR ENROLLED IN VARIOUS BARIATRIC/METABOLIC SURGERY-RELATED PATHOPHYSIOLOGIC MECHANISMS. ABCD-ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA 2017; 29:272-275. [PMID: 28076485 PMCID: PMC5225870 DOI: 10.1590/0102-6720201600040014] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/05/2016] [Accepted: 08/02/2016] [Indexed: 12/31/2022]
Abstract
Introduction: Glucagon-like peptide-2 (GLP-2) is a gastrointestinal hormone whose effects are predominantly trophic on the intestinal mucosa. Aim: Critically evaluate the current literature on the influence of bariatric/metabolic surgery on the levels of GLP-2 and its potential clinical implications. Method s: Narrative review through online research on the databases Medline and Lilacs. There were six prospective human studies, two cross-sectional human studies, and three experimental animal studies selected. Results: There is evidence demonstrating significant increase in the levels of GLP-2 following gastric bypass, Scopinaro operation, and sleeve gastrectomy. There are no differences between gastric bypass and sleeve gastrectomy in regards to the increase in the GLP-2 levels. There is no correlation between the postoperative levels of GLP-2 and the occurrence of adequate or insufficient postoperative weight loss. Conclusion: GLP-2 plays significant roles on the regulation of nutrient absorption, permeability of gut mucosa, control of bone resorption, and regulation of satiety. The overall impact of these effects potentially exerts a significant adaptive or compensatory effect within the context of varied bariatric surgical techniques.
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Affiliation(s)
| | | | | | | | - Bruno Geloneze
- Research Laboratory in Metabology and Diabetes (Limed), State University of Campinas - Unicamp, Campinas, SP, Brazil
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Adami GF, Scopinaro N, Cordera R. Adipokine Pattern After Bariatric Surgery: Beyond the Weight Loss. Obes Surg 2016; 26:2793-2801. [DOI: 10.1007/s11695-016-2347-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
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Lutz TA, Bueter M. The Use of Rat and Mouse Models in Bariatric Surgery Experiments. Front Nutr 2016; 3:25. [PMID: 27547753 PMCID: PMC4974272 DOI: 10.3389/fnut.2016.00025] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2016] [Accepted: 07/26/2016] [Indexed: 12/11/2022] Open
Abstract
Animal models have been proven to be a crucial tool for investigating the physiological mechanisms underlying bariatric surgery in general and individual techniques in particular. By using a translational approach, most of these studies have been performed in rodents and have helped to understand how bariatric surgery may or may not work. However, data from studies using animal models should always be critically evaluated for their transferability to the human physiology. It is, therefore, the aim of this review to summarize both advantages and limitations of data generated by animal based experiments designed to investigate and understand the physiological mechanisms at the root of bariatric surgery.
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Affiliation(s)
- Thomas A Lutz
- Vetsuisse Faculty, Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland
| | - Marco Bueter
- Centre for Integrative Human Physiology, University of Zurich, Zurich, Switzerland; Department of Surgery, Division of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland
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Abstract
Obesity and its associated medical conditions continue to increase and add significant burden to patients, as well as health-care systems, worldwide. Bariatric surgery is the most effective treatment for severe obesity and its comorbidities, and resolution of diabetes is weight loss-independent in the case of some operations. Although these weight-independent effects are frequently described clinically, the mechanisms behind them are not well understood and remain an intense area of focus in the growing field of metabolic and bariatric surgery. Perceptions of the mechanisms responsible for the beneficial metabolic effects of metabolic/bariatric operations have shifted from being mostly restrictive and malabsorption over the last 10 to 15 years to being more neuro-hormonal in origin. In this review, we describe recent basic and clinical findings of the major clinical procedures (adjustable gastric banding, vertical sleeve gastrectomy, Roux-en-Y gastric bypass, and biliopancreatic diversion) as well as other experimental procedures (ileal interposition and bile diversion) that recapitulate many of the metabolic effects of these complex operations in a simpler fashion. As the role of bile acids and the gut microbiome on metabolism is becoming increasingly well described, their potential roles in these improvements following metabolic surgery are becoming better appreciated. Bile acid and gut microbiome changes, in light of recent developments, are discussed in the context of these surgical procedures, as well as their implications for future study.
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Affiliation(s)
- Vance L Albaugh
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA
| | - C Robb Flynn
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA
| | - Robyn A Tamboli
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA
| | - Naji N Abumrad
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA
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Mumphrey MB, Hao Z, Townsend RL, Patterson LM, Berthoud HR. Sleeve Gastrectomy Does Not Cause Hypertrophy and Reprogramming of Intestinal Glucose Metabolism in Rats. Obes Surg 2016; 25:1468-73. [PMID: 25566744 DOI: 10.1007/s11695-014-1547-9] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND Clinical studies have shown similar rapid improvements in body mass and glycemic control after Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG). Evidence suggests that adaptive intestinal tissue growth and reprogramming of intestinal glucose disposal play a key role in the beneficial effects on glucose homeostasis after RYGB, but it is not known whether such adaptive changes also occur after sleeve gastrectomy. METHODS High-fat diet-induced obese rats were subjected to either VSG or RYGB, and intestinal growth and functional adaptations were assessed by using morphometric, immunohistochemical, and immuno-blot techniques, 3 months after surgery or sham surgery. RESULTS The cross-sectional areas of the Roux and common limbs are significantly increased after RYGB compared with sham surgery (Roux limb: 17.1 ± 4.0 vs. 5.5 ± 0.1 mm(2); common limb: 11.7 ± 0.6 vs. 5.1 ± 0.5 mm(2); p < 0.01), but the cross-sectional area of the corresponding jejunum is not different from controls after VSG. Similarly, mucosal thickness and the number of GLP-1 cells are not increased after VSG. Protein expression of hexokinase II is increased fourfold (p < 0.01) in the Roux limb after RYGB, but not in the jejunum after VSG. CONCLUSIONS Adaptive hypertrophy and reprogramming of glucose metabolism in the small intestine are not necessary for VSG to improve body composition and glycemic control. The similar beneficial effects of VSG and RYGB on glucose homeostasis might be mediated by different mechanisms.
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Affiliation(s)
- Michael B Mumphrey
- Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University System, 6400 Perkins Road, Baton Rouge, LA, 70808, USA
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Pappachan JM, Viswanath AK. Metabolic surgery: A paradigm shift in type 2 diabetes management. World J Diabetes 2015; 6:990-998. [PMID: 26240695 PMCID: PMC4515448 DOI: 10.4239/wjd.v6.i8.990] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/12/2015] [Revised: 04/30/2015] [Accepted: 05/28/2015] [Indexed: 02/05/2023] Open
Abstract
Obesity and type 2 diabetes mellitus (T2DM) are major public health issues globally over the past few decades. Despite dietary interventions, lifestyle modifications and the availability of several pharmaceutical agents, management of T2DM with obesity is a major challenge to clinicians. Metabolic surgery is emerging as a promising treatment option for the management of T2DM in the obese population in recent years. Several observational studies and a few randomised controlled trials have shown clear benefits of various bariatric procedures in obese individuals in terms of improvement or remission of T2DM and multiple other health benefits such as improvement of hypertension, obstructive sleep apnoea, osteoarthritis and non-alcoholic fatty liver disease. Uncertainties about the long-term implications of metabolic surgery such as relapse of T2DM after initial remission, nutritional and psychosocial complications and the optimal body mass index for different ethnic groups exist. The article discusses the major paradigm shift in recent years in the management of T2DM after the introduction of metabolic surgery.
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Baraboi ED, Li W, Labbé SM, Roy MC, Samson P, Hould FS, Lebel S, Marceau S, Biertho L, Richard D. Metabolic changes induced by the biliopancreatic diversion in diet-induced obesity in male rats: the contributions of sleeve gastrectomy and duodenal switch. Endocrinology 2015; 156:1316-29. [PMID: 25646712 DOI: 10.1210/en.2014-1785] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The mechanisms underlying the body weight and fat loss after the biliopancreatic diversion with duodenal switch (BPD/DS) remain to be fully delineated. The aim of this study was to examine the contributions of the two main components of BPD/DS, namely sleeve gastrectomy (SG) and duodenal switch (DS), on energy balance changes in rats rendered obese with a high-fat (HF) diet. Three different bariatric procedures (BPD/DS, SG, and DS) and three sham surgeries were performed in male Wistar rats. Sham-operated animals fed HF were either fed ad libitum (Sham HF) or pair weighed (Sham HF PW) by food restriction to the BPD/DS rats. A group of sham-operated rats was kept on standard chow and served as normal diet control (Sham Chow). All three bariatric surgeries resulted in a transient reduction in food intake. SG per se induced a delay in body weight gain. BPD/DS and DS led to a noticeable gut malabsorption and a reduction in body weight and fat gains along with significant elevations in plasma levels of glucagon-like peptide-1(7-36) and peptide YY. BPD/DS and DS elevated energy expenditure above that of Sham HF PW during the dark phase. However, they reduced the volume, oxidative metabolism, and expression of thermogenic genes in interscapular brown adipose tissue. Altogether the results of this study suggest that the DS component of the BPD/DS, which led to a reduction in digestible energy intake while sustaining energy expenditure, plays a key role in the improvement in the metabolic profile led by BPD/DS in rats fed a HF diet.
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Affiliation(s)
- Elena-Dana Baraboi
- Institut Universitaire de Cardiologie et de Pneumologie de Québec, Chemin Sainte-Foy, Québec, Canada G1V 4G5
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Adam CL, Williams PA, Garden KE, Thomson LM, Ross AW. Dose-dependent effects of a soluble dietary fibre (pectin) on food intake, adiposity, gut hypertrophy and gut satiety hormone secretion in rats. PLoS One 2015; 10:e0115438. [PMID: 25602757 PMCID: PMC4300082 DOI: 10.1371/journal.pone.0115438] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Accepted: 11/25/2014] [Indexed: 12/16/2022] Open
Abstract
Soluble fermentable dietary fibre elicits gut adaptations, increases satiety and potentially offers a natural sustainable means of body weight regulation. Here we aimed to quantify physiological responses to graded intakes of a specific dietary fibre (pectin) in an animal model. Four isocaloric semi-purified diets containing 0, 3.3%, 6.7% or 10% w/w apple pectin were offered ad libitum for 8 or 28 days to young adult male rats (n = 8/group). Measurements were made of voluntary food intake, body weight, initial and final body composition by magnetic resonance imaging, final gut regional weights and histology, and final plasma satiety hormone concentrations. In both 8- and 28-day cohorts, dietary pectin inclusion rate was negatively correlated with food intake, body weight gain and the change in body fat mass, with no effect on lean mass gain. In both cohorts, pectin had no effect on stomach weight but pectin inclusion rate was positively correlated with weights and lengths of small intestine and caecum, jejunum villus height and crypt depth, ileum crypt depth, and plasma total glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) concentrations, and at 8 days was correlated with weight and length of colon and with caecal mucosal depth. Therefore, the gut's morphological and endocrine adaptations were dose-dependent, occurred within 8 days and were largely sustained for 28 days during continued dietary intervention. Increasing amounts of the soluble fermentable fibre pectin in the diet proportionately decreased food intake, body weight gain and body fat content, associated with proportionately increased satiety hormones GLP-1 and PYY and intestinal hypertrophy, supporting a role for soluble dietary fibre-induced satiety in healthy body weight regulation.
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Affiliation(s)
- Clare L. Adam
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
| | - Patricia A. Williams
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
| | - Karen E. Garden
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
| | - Lynn M. Thomson
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
| | - Alexander W. Ross
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
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Abstract
BACKGROUND Bariatric surgical procedures are classified by their presumed mechanisms of action: restrictive, malabsorptive or a combination of both. However, this dogma is questionable and remains unproven. We investigated post-operative changes in nutrient absorption and transit time following bariatric surgery. METHODS Participants were recruited into four groups: obese controls (body mass index (BMI) >30 kg/m2, n = 7), adjustable gastric banding (n = 6), Roux-en-Y gastric bypass (RYGB, n = 7) and biliopancreatic diversion with duodenal switch (DS, n = 5). Participants underwent sulphasalazine/sulphapyridine tests (oro-caecal transit time); fasting plasma citrulline (functional enterocyte mass); 3 days faecal collection for faecal elastase 1 (FE-1); calprotectin (FCp); faecal fatty acids (pancreatic exocrine function, gut inflammation and fat excretion, respectively); and 5 h D-xylose, L-rhamnose and lactulose test (intestinal absorption and permeability). RESULTS Age and gender were not different but BMI differed between groups (p = 0.001). No difference in oro-caecal transit time (p = 0.935) or functional enterocyte mass (p = 0.819) was detected. FCp was elevated post-RYGB vs. obese (p = 0.016) and FE-1 was reduced post-RYGB vs. obese (p = 0.002). Faecal fat concentrations were increased post-DS vs. obese (p = 0.038) and RYGB (p = 0.024) and were also higher post-RYGB vs. obese (p = 0.033). Urinary excretion of D-xylose and L-rhamnose was not different between the groups; however, lactulose/rhamnose ratio was elevated post-DS vs. other groups (all p < 0.02), suggesting increased intestinal permeability. CONCLUSIONS Following RYGB, there are surprisingly few abnormalities or indications of severe malabsorption of fats or sugars. Small bowel adaptation after bariatric surgery may be key to understanding the mechanisms responsible for the beneficial metabolic effects of these operations.
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Jurowich CF, Otto C, Rikkala PR, Wagner N, Vrhovac I, Sabolić I, Germer CT, Koepsell H. Ileal Interposition in Rats with Experimental Type 2 Like Diabetes Improves Glycemic Control Independently of Glucose Absorption. J Diabetes Res 2015; 2015:490365. [PMID: 26185767 PMCID: PMC4491588 DOI: 10.1155/2015/490365] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 06/05/2015] [Accepted: 06/07/2015] [Indexed: 02/08/2023] Open
Abstract
Bariatric operations in obese patients with type 2 diabetes often improve diabetes before weight loss is observed. In patients mainly Roux-en-Y-gastric bypass with partial stomach resection is performed. Duodenojejunal bypass (DJB) and ileal interposition (IIP) are employed in animal experiments. Due to increased glucose exposition of L-cells located in distal ileum, all bariatric surgery procedures lead to higher secretion of antidiabetic glucagon like peptide-1 (GLP-1) after glucose gavage. After DJB also downregulation of Na(+)-d-glucose cotransporter SGLT1 was observed. This suggested a direct contribution of decreased glucose absorption to the antidiabetic effect of bariatric surgery. To investigate whether glucose absorption is also decreased after IIP, we induced diabetes with decreased glucose tolerance and insulin sensitivity in male rats and investigated effects of IIP on diabetes and SGLT1. After IIP, we observed weight-independent improvement of glucose tolerance, increased insulin sensitivity, and increased plasma GLP-1 after glucose gavage. The interposed ileum was increased in diameter and showed increased length of villi, hyperplasia of the epithelial layer, and increased number of L-cells. The amount of SGLT1-mediated glucose uptake in interposed ileum was increased 2-fold reaching the same level as in jejunum. Thus, improvement of glycemic control by bariatric surgery does not require decreased glucose absorption.
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Affiliation(s)
- Christian Ferdinand Jurowich
- Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany
| | - Christoph Otto
- Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany
| | - Prashanth Reddy Rikkala
- Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, 97070 Würzburg, Germany
| | - Nicole Wagner
- Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, 97070 Würzburg, Germany
| | - Ivana Vrhovac
- Molecular Toxicology Unit, Institute for Medical Research & Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, Croatia
| | - Ivan Sabolić
- Molecular Toxicology Unit, Institute for Medical Research & Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, Croatia
| | - Christoph-Thomas Germer
- Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany
| | - Hermann Koepsell
- Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, 97070 Würzburg, Germany
- Department of Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute, University of Würzburg, Julius-von-Sachs-Platz 2, 97082 Würzburg, Germany
- *Hermann Koepsell:
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19
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Preserve common limb in duodenal-jejunal bypass surgery benefits rats with type 2-like diabetes. Obes Surg 2014; 24:405-11. [PMID: 24190437 DOI: 10.1007/s11695-013-1103-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/26/2022]
Abstract
BACKGROUND In order to understand the underlying mechanisms by which weight loss surgeries improve metabolic profiles in type 2 diabetes mellitus (T2DM) patients and to evaluate the relevance of the length of the common limb in modulating various aspects of metabolism, we performed regular duodenal-jejunal bypass (DJB) and long-limb DJB (LL-DJB) surgeries in Goto-Kakizaki (GK) rats and compared their effects on glycemic control. METHODS Male GK rats at 12 weeks of age were used for this study. Body weight, food intake, fasting glucose, glucagon-like peptide-1 (GLP-1) level, glucose tolerance, insulin sensitivity, cholesterol and triglycerides levels, and fecal energy content were monitored for 26 weeks after the two types of surgeries. RESULTS We performed systematic analyses on GK rats after DJB or long-limb surgeries. Both procedures prevented body weight gain, reduced blood glucose and lipid levels, increased GLP-1 levels, and led to better insulin sensitivity. In general, LL-DJB displayed better effects than DJB, except that both surgeries caused similar increase in GLP-1 levels. CONCLUSIONS Both DJB and LL-DJB surgeries triggered beneficial effects in GK rats. LL-DJB showed better outcomes than DJB, which may be due to reduced food intake and higher fecal energy content. This indicates that the length of the common limb could influence metabolic profiles of surgery recipients.
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Quercia I, Dutia R, Kotler DP, Belsley S, Laferrère B. Gastrointestinal changes after bariatric surgery. DIABETES & METABOLISM 2013; 40:87-94. [PMID: 24359701 DOI: 10.1016/j.diabet.2013.11.003] [Citation(s) in RCA: 90] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/08/2013] [Revised: 11/21/2013] [Accepted: 11/22/2013] [Indexed: 12/23/2022]
Abstract
Severe obesity is a preeminent health care problem that impacts overall health and survival. The most effective treatment for severe obesity is bariatric surgery, an intervention that not only maintains long-term weight loss but also is associated with improvement or remission of several comorbidies including type 2 diabetes mellitus. Some weight loss surgeries modify the gastrointestinal anatomy and physiology, including the secretions and actions of gut peptides. This review describes how bariatric surgery alters the patterns of gastrointestinal motility, nutrient digestion and absorption, gut peptide release, bile acids and the gut microflora, and how these changes alter energy homeostasis and glucose metabolism.
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Affiliation(s)
- I Quercia
- New York Obesity Nutrition Research Center, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, 1111, Amsterdam Avenue, 1034 New York, NY 10025, USA; Department of Medicine, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA
| | - R Dutia
- New York Obesity Nutrition Research Center, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, 1111, Amsterdam Avenue, 1034 New York, NY 10025, USA; Department of Medicine, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA
| | - D P Kotler
- Division of Gastroenterology and Liver Disease, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA; Department of Medicine, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA; Columbia University College of Physicians and Surgeons, New York, NY 10025, USA
| | - S Belsley
- Department of Surgery, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA; Columbia University College of Physicians and Surgeons, New York, NY 10025, USA
| | - B Laferrère
- New York Obesity Nutrition Research Center, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, 1111, Amsterdam Avenue, 1034 New York, NY 10025, USA; Division of Endocrinology, Diabetes and Nutrition, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA; Department of Medicine, St Luke's-Roosevelt Hospital Center, New York, NY 10025, USA; Columbia University College of Physicians and Surgeons, New York, NY 10025, USA.
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Drucker DJ, Yusta B. Physiology and pharmacology of the enteroendocrine hormone glucagon-like peptide-2. Annu Rev Physiol 2013; 76:561-83. [PMID: 24161075 DOI: 10.1146/annurev-physiol-021113-170317] [Citation(s) in RCA: 242] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
Abstract
Glucagon-like peptide-2 (GLP-2) is a 33-amino-acid proglucagon-derived peptide secreted from enteroendocrine L cells. GLP-2 circulates at low basal levels in the fasting period, and plasma levels rise rapidly after food ingestion. Renal clearance and enzymatic inactivation control the elimination of bioactive GLP-2. GLP-2 increases mesenteric blood flow and activates proabsorptive pathways in the gut, facilitating nutrient absorption. GLP-2 also enhances gut barrier function and induces proliferative and cytoprotective pathways in the small bowel. The actions of GLP-2 are transduced via a single G protein-coupled receptor (GLP-2R), expressed predominantly within the gastrointestinal tract. Disruption of GLP-2R signaling increases susceptibility to gut injury and impairs the adaptive mucosal response to refeeding. Sustained augmentation of GLP-2R signaling reduces the requirement for parenteral nutrition in human subjects with short-bowel syndrome. Hence GLP-2 integrates nutrient-derived signals to optimize mucosal integrity and energy absorption.
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Affiliation(s)
- Daniel J Drucker
- Department of Medicine, Mount Sinai Hospital, Lunenfeld Tanenbaum Research Institute, University of Toronto, Toronto, Ontario, Canada M5G 1X5; ,
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Hansen CF, Bueter M, Theis N, Lutz T, Paulsen S, Dalbøge LS, Vrang N, Jelsing J. Hypertrophy dependent doubling of L-cells in Roux-en-Y gastric bypass operated rats. PLoS One 2013; 8:e65696. [PMID: 23776529 PMCID: PMC3679162 DOI: 10.1371/journal.pone.0065696] [Citation(s) in RCA: 88] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/09/2012] [Accepted: 04/29/2013] [Indexed: 12/31/2022] Open
Abstract
Background and Aims Roux-en-Y gastric bypass (RYGB) leads to a rapid remission of type 2 diabetes mellitus (T2DM), but the underlying mode of action remains incompletely understood. L-cell derived gut hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are thought to play a central role in the anti-diabetic effects of RYGB; therefore, an improved understanding of intestinal endocrine L-cell adaptability is considered pivotal. Methods The full rostrocaudal extension of the gut was analyzed in rats after RYGB and in sham-operated controls ad libitum fed or food restricted to match the body weight of RYGB rats. Total number of L-cells, as well as regional numbers, densities and mucosa volumes were quantified using stereological methods. Preproglucagon and PYY mRNA transcripts were quantified by qPCR to reflect the total and relative hormone production capacity of the L-cells. Results RYGB surgery induced hypertrophy of the gut mucosa in the food exposed regions of the small intestine coupled with a doubling in the total number of L-cells. No changes in L-cell density were observed in any region regardless of surgery or food restriction. The total gene expression capacity of the entire gut revealed a near 200% increase in both PYY and preproglucagon mRNA levels in RYGB rats associated with both increased L-cell number as well as region-specific increased transcription per cell. Conclusions Collectively, these findings indicate that RYGB in rats is associated with gut hypertrophy, an increase in L-cell number, but not density, and increased PYY and preproglucagon gene expression. This could explain the enhanced gut hormone dynamics seen after RYGB.
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Affiliation(s)
- Carl Frederik Hansen
- Department of Histology, Gubra, Hørsholm, Denmark
- Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark
| | - Marco Bueter
- Department of Visceral and Transplant Surgery, University Hospital Zurich, Zurich, Switzerland
- Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland
| | - Nadine Theis
- Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | - Thomas Lutz
- Center of Integrative Human Physiology, University of Zurich, Zurich, Switzerland
- Institute of Veterinary Physiology, Vetsuisse Faculty, University of Zurich, Zurich, Switzerland
| | | | | | - Niels Vrang
- Department of Histology, Gubra, Hørsholm, Denmark
| | - Jacob Jelsing
- Department of Histology, Gubra, Hørsholm, Denmark
- * E-mail:
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Evaluation of Weight Loss Failure, Medical Outcomes, and Personal Experiences after Roux-en-Y Gastric Bypass: A Critical Analysis. ISRN OBESITY 2013; 2013:943423. [PMID: 24555160 PMCID: PMC3901958 DOI: 10.1155/2013/943423] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 12/14/2012] [Accepted: 01/15/2013] [Indexed: 01/06/2023]
Abstract
Background. Roux-en-Y gastric bypass (RYGB) is considered an effective and well-tolerated surgical procedure. In this retrospective study, we critically assessed efficacy and negative personal experiences (NPEs) after RYGB with a self-administered questionnaire (SAQ). Methods. This questionnaire study included 404 patients who had undergone RYGB. Analysis was performed using data from medical records, referral letters, and SAQs at an average of 33 months after procedure. We evaluated the occurrence of hypertension, CPEP use and type 2 diabetes mellitus (T2DM), the amount of excess weight loss, degree of satisfaction and negative personal experiences (NPEs) related to the procedure, and adherence to a dedicated life style program and (non)attendance to followup. consults after surgery. Results. 42.3% of all SAQs were evaluable for analysis. T2DM remained similar, while hypertension and continuous positive airway pressure (CPAP) use decreased significantly; excess weight loss of ≥40% was reported in 69% and of <40% in 19%, a significant improvement. Absolute weight gain was reported in 10.5%, fatigue in 44.4%, dysphagia in 11.6%, and other NPEs in 7.6%. Dissatisfaction over weight loss was reported in 9.4%. Mean number of follow-up visits was 9.6 per respondent, while nonattendance of any follow-up visit consults occurred in 1.8%. Conclusions. The use of post-RYGB SAQs provided evaluable data in 42.3%. Treatment failure after RYGB appears to be relevant, encouraging the use of SAQ studies in large cohorts.
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de Luis D, Pacheco D, Conde R, Primo D, Aller R, Izaola O. Basal GLP-1 levels in morbidly obese patients following biliopancreatic diversion surgery. ANNALS OF NUTRITION AND METABOLISM 2012; 61:70-3. [PMID: 22846622 DOI: 10.1159/000339378] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/22/2011] [Accepted: 05/09/2012] [Indexed: 12/16/2022]
Abstract
BACKGROUND Previous studies addressing the changes of glucagon-like peptide-1 (GLP-1) concentrations in morbidly obese patients after bariatric surgery have demonstrated conflicting results. The aim of the present study was to investigate the changes in serum GLP-1 levels 9 months after biliopancreatic diversion in morbidly obese patients without diabetes mellitus. METHODS A sample of 40 morbidly obese patients without diabetes mellitus was enrolled. Biochemical and anthropometrical evaluations were conducted at basal and 9 months after surgery. RESULTS The mean patient age was 46.6 ± 13.1 years, and the mean preoperative body mass index (BMI) was 47.1 ± 18.1. A significant decrease in BMI, weight, waist circumference, fat mass, glucose, LDL cholesterol, total cholesterol, and triglyceride levels was observed after 9 months. Serum basal GLP-1 levels did not change after surgery (0.65 ± 0.18 ng/ml vs. 0.66 ± 0.17 ng/ml; n.s.). Postsurgical correlation analysis showed a negative association between basal GLP-1 and HDL cholesterol (r = -0.57; p < 0.01). CONCLUSIONS Fasting GLP-1 concentrations did not change after massive weight loss with biliopancreatic diversion in morbidly obese patients without diabetes mellitus.
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Affiliation(s)
- Daniel de Luis
- Institute of Endocrinology and Nutrition, Medicine School, Unit of Investigation, Surgical Department and Endocrinology Department, Hospital Rio Hortega, University of Valladolid, Valladolid, Spain.
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Scopinaro N, Adami GF, Papadia FS, Camerini G, Carlini F, Briatore L, D'Alessandro G, Parodi C, Weiss A, Andraghetti G, Catalano M, Cordera R. The effects of biliopancreatic diversion on type 2 diabetes mellitus in patients with mild obesity (BMI 30-35 kg/m2) and simple overweight (BMI 25-30 kg/m2): a prospective controlled study. Obes Surg 2012; 21:880-8. [PMID: 21541815 DOI: 10.1007/s11695-011-0407-0] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Beneficial effects of BPD on T2DM in BMI >35 kg/m(2) patients are far better than those in patients with BMI 25-35. This study was aimed at investigating if a similar difference exists between patients with mild obesity (OB, BMI 30-35) or simple overweight (OW, BMI 25-30). METHODS Fifteen OB (six M) and 15 OW (13 M), diabetic for ≥ 3 years, with HbA1c ≥ 7.5% despite medical therapy, underwent BPD. OB/OW: age 55.1 ± 8.0/57.8 ± 6.7 years, BMI 33.1 ± 1.5/28.0 ± 1.3 kg/m(2), diabetes duration 11.6 ± 8.0/11.1 ± 6.1 years, insulin therapy 4/8 p. FSG and HbA1c were determined preoperatively and up to 2 years. Insulin resistance and beta-cell function were explored by means of HOMA-IR and IVGTT (AIR). Thirty-eight diabetic patients on medical therapy served as controls. RESULTS Mean BMI stabilized around 27 since the 4th month in OB, and 24 since 1st month in OW. FSG in OB/OW preop, 1, 12, 24 months: 234 ± 76/206 ± 62 mg/dL, 154 ± 49/176 ± 75, 131 ± 32/167 ± 48, 134 ± 41/154 ± 41 (cross-sectional n.s. at all times); HbA1c: 9.5 ± 1.6/9.1 ± 1.3, 7.3 ± 1.1/7.3 ± 1.2, 5.9 ± 0.6/7.1 ± 1.1 (p < 0.01), 5.9 ± 0.9/6.9 ± 1.1 (p < 0.01). HOMA-IR, preoperatively 10.7 ± 5.8/7.5 ± 5.4, went below 3.0 at 1 month and remained such until 2 years in both groups. AIR, preoperatively 1.11 ± 3.17/1.27 ± 2.68 μIU/mL, in OB significantly increased at 4 months to 7.63 ± 5.79, maintained up to 2 years with 6.95 ± 3.19, whereas in OW, statistical significance was reached only at 2 years with 5.02 ± 4.87. CONCLUSIONS Significantly different BPD effect, thus biological severity of T2DM, also exists between mildly obese and simply overweight patients. The rise of AIR allows hoping that an increase of beta-cell mass may occur in the long run.
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Affiliation(s)
- Nicola Scopinaro
- Department of Surgery, University of Genoa Medical School, Genoa, Italy.
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Effects of sleeve gastrectomy surgery with modified jejunoileal bypass on body weight, food intake and metabolic hormone levels of rats. ACTA ACUST UNITED AC 2011; 31:784-788. [DOI: 10.1007/s11596-011-0677-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2011] [Indexed: 10/14/2022]
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Alam I, Stephens JW, Fielding A, Lewis KE, Lewis MJ, Baxter JN. Temporal changes in glucose and insulin homeostasis after biliopancreatic diversion and laparoscopic adjustable gastric banding. Surg Obes Relat Dis 2011; 8:752-63. [PMID: 22177976 DOI: 10.1016/j.soard.2011.10.018] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/26/2011] [Revised: 09/17/2011] [Accepted: 10/17/2011] [Indexed: 01/22/2023]
Abstract
BACKGROUND Obesity surgery is associated with improvement in type 2 diabetes mellitus. Our aim was to examine the effects of biliopancreatic diversion (BPD) and laparoscopic adjustable gastric banding (LAGB) on the body mass index, fasting insulin level, glucose level, and insulin resistance in morbidly obese subjects with type 2 diabetes mellitus. The setting was the Department of Surgery, Morriston Hospital (Swansea, Wales, United Kingdom). METHODS A total of 13 morbidly obese patients (7 BPD, 6 LAGB) underwent serial measurements of fasting glucose and insulin at baseline, immediately after surgery (days 1-7), and 1, 6, and 12 months postoperatively. The homeostasis model of assessment-insulin resistance was calculated. RESULTS In the BPD group, the glucose levels had normalized by day 3 (5.6 ± 1 mmol/L) and the difference was statistically significant at 6 and 12 months postoperatively (5 ± .7 and 4.4 ± .5 mmol/L, respectively). The insulin levels had improved from day 1, and the difference was statistically significant at days 2, 5, 6, and 7 (19 ± 9, 14.2 ± 7, 15.2 ± 8, and 17.4 ± 8 mU/L, respectively). All diabetes medications were stopped on the fourth postoperative day. In the LAGB group, no statistically significant changes were seen in the glucose levels. Statistically significant changes in insulin were seen on days 1 and 2 (19 ± 13 and 13 ± 6.5 mU/L, respectively). The homeostatic model of assessment-insulin resistance had improved in both groups (BPD, 1.6 ± 1.2, P < .01; and LAGB, 4.3 ± 1.4, P < .05). CONCLUSION BPD causes immediate remission of type 2 diabetes mellitus. Leptin might play an important role in the early improvement of insulin resistance in fasting states after BPD. In the LAGB group, glucose homeostasis improved, but the patients still required diabetes medications, although the dosages were reduced.
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Affiliation(s)
- I Alam
- Department of Surgery, Morriston Hospital, ABM University Health Board, Swansea, Wales, United Kingdom.
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Scott WR, Batterham RL. Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy: understanding weight loss and improvements in type 2 diabetes after bariatric surgery. Am J Physiol Regul Integr Comp Physiol 2011; 301:R15-27. [PMID: 21474429 DOI: 10.1152/ajpregu.00038.2011] [Citation(s) in RCA: 76] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Obesity increases the likelihood of diseases like type 2 diabetes (T2D), heart disease, and cancer, and is one of the most serious public health problems of this century. In contrast to ineffectual prevention strategies, lifestyle modifications, and pharmacological therapies, bariatric surgery is a very effective treatment for morbid obesity and also markedly improves associated comorbidities like T2D. However, weight loss and resolution of T2D after bariatric surgery is heterogeneous and specific to type of bariatric procedure performed. Conventional mechanisms like intestinal malabsorption and gastric restriction do not fully explain this, and potent changes in appetite and the enteroinsular axis, as a result of anatomical reorganization and altered hormonal, neuronal, and nutrient signaling, are the portended cause. Uniquely these signaling changes appear to override vigorous homeostatic defenses of stable body weight and compelling self-gratifying motivations to eat and to reverse defects in beta-cell function and insulin sensitivity. Here we review mechanisms of weight loss and T2D resolution after Roux-en-Y gastric bypass and laparoscopic sleeve gastrectomy bariatric surgery, two markedly different procedures with robust clinical outcomes.
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Affiliation(s)
- William R Scott
- Centre for Obesity Research, Dept. of Medicine, Rayne Institute, University College London, WC1E 6JJ, UK
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Mendieta-Zerón H, Larrad-Jiménez Á, Burrell MA, Rodríguez MM, Da Boit K, Frühbeck G, Diéguez C. Biliopancreatic diversion induces villi elongation and cholecystokinin and ghrelin increase. Diabetes Metab Syndr 2011; 5:66-70. [PMID: 22813405 DOI: 10.1016/j.dsx.2012.02.012] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
INTRODUCTION Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. Our aim was to evaluate, in Sprague-Dawley rats, the histological and gut hormonal changes after Larrad-biliopancreatic diversion (Larrad-BPD). MATERIALS AND METHODS Rats randomly underwent the following protocols: Larrad-BPD (n=4) versus pair fed (PF) (n=4). Weight and food intake were measured every day. By immunohistochemistry ghrelin was examined in the stomach, while cholecystokinin (CCK), glucagon-like-peptide-1 (GLP-1), peptide YY (PYY) and serotonin (5-HT) expression were analyzed in alimentary limb and ileum following or not the Larrad-BPD. RESULTS Larrad-BPD rats exhibited significant (P<0.05) weight loss compared to PF rats. Villi enlongation was observed in Larrad-BPD rats. In residual stomach, ghrelin was diminished. In the alimentary limb, ghrelin and CCK positive cells were detected more than in the ileum of PF rats. GLP-1 expression was decreased and PYY expression was absent after Larrad-BPD compared with PF rats. DISCUSSION Larrad-BPD is followed by histological changes and a pleiotropic gut endocrine response aimed to compensate the reduction of intestinal area exposed to food. Until now, the hormones responsible for the intestinal hypertrophy have not been defined.
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Affiliation(s)
- Hugo Mendieta-Zerón
- Medical Research Center (CICMED), Autonomous University of the State of Mexico (UAEMEx), Toluca, Mexico.
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Ashrafian H, Bueter M, Ahmed K, Suliman A, Bloom SR, Darzi A, Athanasiou T. Metabolic surgery: an evolution through bariatric animal models. Obes Rev 2010; 11:907-20. [PMID: 20051020 DOI: 10.1111/j.1467-789x.2009.00701.x] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/13/2023]
Abstract
Metabolic surgery was developed through the application and experience gained from bariatric or weight loss procedures. Much of our knowledge from the procedures comes from the study of animal models, where they have revealed anatomic feasibility, systemic physiological elements and cellular metabolic effects. The first generation of operation included the jejunoileal bypass and partial ileal bypass that led to the development of the current procedures including Roux-en-Y gastric bypass, biliopancreatic diversion, adjustable gastric banding and sleeve gastrectomy. These operations carry significant metabolic benefits and can reduce the risk of diabetes, heart disease and cancer. Further insights from these animal models can reveal genetic, molecular and systemic effects that can enhance and develop the next generation of metabolic operations.
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Affiliation(s)
- H Ashrafian
- Department of Surgery and Cancer, Imperial College, London, UK.
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Heber D, Greenway FL, Kaplan LM, Livingston E, Salvador J, Still C. Endocrine and nutritional management of the post-bariatric surgery patient: an Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab 2010; 95:4823-43. [PMID: 21051578 DOI: 10.1210/jc.2009-2128] [Citation(s) in RCA: 294] [Impact Index Per Article: 19.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
OBJECTIVE We sought to provide guidelines for the nutritional and endocrine management of adults after bariatric surgery, including those with diabetes mellitus. The focus is on the immediate postoperative period and long-term management to prevent complications, weight regain, and progression of obesity-associated comorbidities. The treatment of specific disorders is only summarized. PARTICIPANTS The Task Force was composed of a chair, five additional experts, a methodologist, and a medical writer. It received no corporate funding or remuneration. CONCLUSIONS Bariatric surgery is not a guarantee of successful weight loss and maintenance. Increasingly, patients regain weight, especially those undergoing restrictive surgeries such as laparoscopic banding rather than malabsorptive surgeries such as Roux-en-Y bypass. Active nutritional patient education and clinical management to prevent and detect nutritional deficiencies are recommended for all patients undergoing bariatric surgery. Management of potential nutritional deficiencies is particularly important for patients undergoing malabsorptive procedures, and strategies should be employed to compensate for food intolerance in patients who have had a malabsorptive procedure to reduce the risk for clinically important nutritional deficiencies. To enhance the transition to life after bariatric surgery and to prevent weight regain and nutritional complications, all patients should receive care from a multidisciplinary team including an experienced primary care physician, endocrinologist, or gastroenterologist and consider enrolling postoperatively in a comprehensive program for nutrition and lifestyle management. Future research should address the effectiveness of intensive postoperative nutritional and endocrine care in reducing morbidity and mortality from obesity-associated chronic diseases.
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Affiliation(s)
- David Heber
- David Geffen School of Medicine at University of California, Los Angeles, California 90095, USA
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Fu SL, Zhu HM. Surgical treatment of morbid obesity and type 2 diabetes mellitus: current situation and future prospects. Shijie Huaren Xiaohua Zazhi 2010; 18:2453-2459. [DOI: 10.11569/wcjd.v18.i23.2453] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Along with social progress and life style transformation, morbid obesity, type 2 diabetes mellitus, and metabolic syndrome are increasingly becoming a great threat to human health. Because conventional conservative treatment has little effect on these diseases, they were considered incurable before. However, surgery shows good results in the treatment of these diseases and has therefore revolutionized their treatment. This review aims to elucidate the therapeutic mechanisms of surgery for morbid obesity and 2 diabetes mellitus and to discuss the current situation and future prospects of surgical treatment of these diseases.
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Ghrelin and PYY3−36 in gastrectomized and vagotomized patients: relations with appetite, energy intake and resting energy expenditure. Eur J Clin Nutr 2010; 64:845-52. [DOI: 10.1038/ejcn.2010.88] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
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Rao RS, Rao V, Kini S. Animal Models in Bariatric Surgery—A Review of the Surgical Techniques and Postsurgical Physiology. Obes Surg 2010; 20:1293-305. [DOI: 10.1007/s11695-010-0135-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Abstract
PURPOSE OF REVIEW The mechanisms by which obesity surgery and in particular gastric bypass cause weight loss are unclear. The review will focus on the concept of alterations in the sense of taste after obesity surgery. RECENT FINDINGS Patients after obesity surgery and gastric bypass in particular change their eating behaviour and adopt healthier food preferences by avoiding high-calorie and high-fat foods. Patients find sweet and fatty meals less pleasant not due to postingestive side effects but through changes in the sense of taste. The acuity for sweet taste increases after gastric bypass potentially leading to increased intensity of perception. Obese patients experience higher activation of their brain taste reward and addiction centres in response to high calorie and fat tasting. Gastric bypass may reverse these taste hedonics, perhaps through the influence on gustatory pathways caused by enhanced gut hormone responses after surgery. SUMMARY Elucidation of the metabolic mechanism behind the alterations in taste after obesity surgery could lead to the development of novel surgical and nonsurgical procedures for the treatment of obesity.
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Kodama Y, Zhao CM, Kulseng B, Chen D. Eating behavior in rats subjected to vagotomy, sleeve gastrectomy, and duodenal switch. J Gastrointest Surg 2010; 14:1502-10. [PMID: 20824380 PMCID: PMC2943575 DOI: 10.1007/s11605-010-1315-7] [Citation(s) in RCA: 12] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/26/2010] [Accepted: 08/09/2010] [Indexed: 01/31/2023]
Abstract
BACKGROUND/AIM Food intake, eating behavior, and metabolic parameters in rats that underwent bilateral truncal vagotomy, sleeve gastrectomy, and duodenal switch procedures were examined. METHODS Rats were subjected to bilateral truncal vagotomy plus pyloroplasty (VTPP), pyloroplasty (PP), laparotomy, sleeve gastrectomy (SG), or duodenal switch (DS; with and without SG). RESULTS VTPP, but neither PP nor laparotomy, reduced body weight (BW; 10%) transiently (1 week postoperatively). SG reduced BW (10%) for 6 weeks, while DS alone or SG followed by DS led to a continuous BW loss from 15% at 1 week to 50% at 8 weeks postoperatively. Food intake was higher and the satiety ratio was lower during the night than the day for all groups of surgeries. Neither VTPP nor SG had measurable effect on food intake, eating behavior and metabolic parameters. DS reduced daily food intake by more than 50%, which was associated with hypercholecystokinin(CCK)emia, reduced meal size and increased satiety ratio, and increased fecal energy content (measured at 8 weeks). CONCLUSIONS Weight loss after VTPP, SG, or DS differed in terms of degree, duration, and underlying mechanisms. DS without SG was most effective in the long-term, probably due to hyperCCKemia-induced reduction in food intake and long-limb intestinal bypass-induced malabsorption.
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Affiliation(s)
- Yosuke Kodama
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Chun-Mei Zhao
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
| | - Bård Kulseng
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Departments of Surgery and Endocrinology, St. Olavs University Hospital, Trondheim, Norway
| | - Duan Chen
- Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
- Department of Cancer Research and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, Laboratory Centre (3rd Floor-East Side), Erling Skjalgssons Gate 1, 7006 Trondheim, Norway
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Zheng H, Shin AC, Lenard NR, Townsend RL, Patterson LM, Sigalet DL, Berthoud HR. Meal patterns, satiety, and food choice in a rat model of Roux-en-Y gastric bypass surgery. Am J Physiol Regul Integr Comp Physiol 2009; 297:R1273-82. [PMID: 19726714 PMCID: PMC2777767 DOI: 10.1152/ajpregu.00343.2009] [Citation(s) in RCA: 144] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/17/2009] [Accepted: 08/31/2009] [Indexed: 12/22/2022]
Abstract
Gastric bypass surgery efficiently and lastingly reduces excess body weight and reverses type 2 diabetes in obese patients. Although increased energy expenditure may also play a role, decreased energy intake is thought to be the main reason for weight loss, but the mechanisms involved are poorly understood. Therefore, the aim of this study was to characterize the changes in ingestive behavior in a rat model of Roux-en-Y gastric bypass surgery (RYGB). Obese (24% body fat compared with 18% in chow-fed controls), male Sprague-Dawley rats maintained for 15 wk before and 4 mo after RYGB or sham-surgery on a two-choice low-fat/high-fat diet, were subjected to a series of tests assessing energy intake, meal patterning, and food choice. Although sham-operated rats gained an additional 100 g body wt during the postoperative period, RYGB rats lost approximately 100 g. Intake of a nutritionally complete and palatable liquid diet (Ensure) was significantly reduced by approximately 50% during the first 2 wk after RYGB compared with sham surgery. Decreased intake was the result of greatly reduced meal size with only partial compensation by meal frequency, and a corresponding increase in the satiety ratio. Similar results were obtained with solid food (regular or high-fat chow) 6 wk after surgery. In 12- to 24-h two-choice liquid or solid diet paradigms with nutritionally complete low- and high-fat diets, RYGB rats preferred the low-fat choice (solid) or showed decreased acceptance for the high-fat choice (liquid), whereas sham-operated rats preferred the high-fat choices. A separate group of rats offered chow only before surgery completely avoided the solid high-fat diet in a choice paradigm. The results confirm anecdotal reports of "nibbling" behavior and fat avoidance in RYGB patients and provide a basis for more mechanistic studies in this rat model.
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Affiliation(s)
- Huiyuan Zheng
- Neurobiology of Nutrition Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, Louisiana70808, USA
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Prospective study of gut hormone and metabolic changes after adjustable gastric banding and Roux-en-Y gastric bypass. Int J Obes (Lond) 2009; 33:786-95. [PMID: 19417773 PMCID: PMC2710396 DOI: 10.1038/ijo.2009.79] [Citation(s) in RCA: 244] [Impact Index Per Article: 15.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
Objective The objective of this study was to quantify hormones that regulate energy and glucose homeostasis in order to establish possible mechanisms for the greater efficacy of Roux-en-Y gastric bypass (RYGB) compared with laparascopic adjustable gastric banding (LAGB) in achieving weight loss and improved insulin sensitivity. Design Longitudinal study of patients undergoing LAGB (n=15) and RYGB (n=28) who were studied prior to surgery and at 2, 12, 26 and 52 wks afterwards. Measurements Fasting blood samples were drawn at each visit. Postprandial blood samples were also obtained prior to surgery and at 26 and 52 wks. Samples were assayed for peptide YY (PYY), ghrelin, glucagon-like peptide-1 (GLP-1), glucose, insulin, leptin, thyrotropic hormone (TSH), free T4 and free T3. Results At one year there was greater weight loss in RYGB compared with LAGB patients (30% vs 15%), but final body mass index was similar (34 vs 33 kg/m2). At wk 52, area under the curve (AUC) for PYY in RYGB subjects was greater than LAGB (P<0.01). GLP-1 levels at 30 min post-meal were three-fold greater after RYGB compared with LAGB (P<0.001). Conversely, ghrelin AUC increased after LAGB at wk 52 (P<0.05) but tended to decrease after RYGB. Fasting glucose, insulin, and leptin, and HOMA-IR decreased in both groups over time but were significantly lower at wk 52 after RYGB compared with LAGB. The change in leptin correlated significantly with weight loss in LAGB (r=0.86) and RYGB (r=0.77), however, HOMA-IR correlated significantly with weight loss only in LAGB (r=0.78), and not RYGB (r=0.15). There was a significant decrease in free T3 (P<0.01) after RYGB. Conclusions Differences in levels of gut hormones may play a role in promoting greater weight loss and insulin sensitivity after RYGB compared with LAGB, however, weight loss may be limited by decreases in free T3 and leptin.
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Ashrafian H, le Roux CW. Metabolic surgery and gut hormones - a review of bariatric entero-humoral modulation. Physiol Behav 2009; 97:620-31. [PMID: 19303889 DOI: 10.1016/j.physbeh.2009.03.012] [Citation(s) in RCA: 66] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2009] [Revised: 03/11/2009] [Accepted: 03/12/2009] [Indexed: 12/12/2022]
Abstract
The global pandemic of obesity is increasing. Inappropriate food intake relative to energy expenditure results in increased adiposity. These factors are partly regulated by signals through the gut-brain and adipose-brain axes. Metabolic operations (otherwise known as Bariatric surgery) offer the most effective results for sustained metabolic improvement and weight loss. They modulate a number of gut hormones that constitute the gut-brain axis. This review summarizes the literature to-date reporting the gut hormone changes associated with these operations and their subsequent effects on appetite. Understanding the anatomical differences between each operation and how these can differentially regulate gut hormonal release can provide new treatments and targets for obesity, appetite and metabolic disorders.
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Affiliation(s)
- Hutan Ashrafian
- Department of Biosurgery and Surgical Technology, Imperial College London, UK
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Lifante JC, Inabnet WB. [Early improvement in Type 2 diabetes in obese patients following gastric bypass and bilio-pancreatic diversion: the role of the entero-insular axis]. ACTA ACUST UNITED AC 2009; 145:549-55. [PMID: 19106885 DOI: 10.1016/s0021-7697(08)74685-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/18/2023]
Abstract
Improvement in Type 2 diabetes is seen in 80-98% of obese diabetic patients who undergo gastric bypass or bilio-pancreatic diversion. This improvement is evident early after the operation before significant weight loss has occurred. Although numerous teams have extensively studied the physiology of this early post-bypass amelioration of type 2 diabetes, the exact mechanism of diabetes remission remains unclear. Studies have focused on changes in the entero-insular axis, which is mediated in part by the interaction of insulinotropic hormones GIP and GIP 1 on the beta islet cells of the pancreas. Other mechanisms which have been postulated focus on the adipo-insular axis; the actions of adiponectin and leptin seem to have an important role in insulin resistance but their action is weight-loss dependent. Post-operative caloric restriction may also contribute to the early resolution of type 2 diabetes observed after gastric bypass and bilio- pancreatic diversion.
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Affiliation(s)
- J-C Lifante
- Department of surgery, Division of GI and endocrine surgery, Columbia University - New York, USA.
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Kamiji MM, Troncon LEA, Suen VMM, de Oliveira RB. Gastrointestinal transit, appetite, and energy balance in gastrectomized patients. Am J Clin Nutr 2009; 89:231-9. [PMID: 19056582 DOI: 10.3945/ajcn.2008.26518] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/14/2022] Open
Abstract
BACKGROUND Alterations in gastrointestinal tract physiology after gastrectomy may affect appetite and energy balance. OBJECTIVE The objective of this study was to examine energy balance, appetite, and gastrointestinal transit in subjects with gastrectomy. DESIGN Seven subjects with total gastrectomy (TG) and 14 subjects with partial gastrectomy (PG), who were free from signs of recurrent disease, and 10 healthy control subjects were studied. Resting energy expenditure (REE) was measured by indirect calorimetry and compared with REE predicted by the Harris-Benedict equation (mREE/pREE%). Gastrointestinal transit was measured by scintigraphy. Habitual food intake was assessed, and appetite was measured during scintigraphy after ingestion of a test meal (361 kcal). RESULTS Body mass index was not different among the groups. mREE/pREE% was higher in patients with PG (P < 0.01) than in control subjects. The TG group showed higher energy intake (P < 0.05) than the PG group and control subjects. Gastric emptying was faster in the PG group than in control subjects, and gastrointestinal transit was accelerated in both PG and TG groups. An intense, precocious postprandial fullness and a relatively early recovery of hunger and prospective consumption sensations were seen in these patients. CONCLUSIONS Patients with PG or TG have higher than predicted energy expenditure, which in TG seems to be compensated for by increased energy intake. These patients have preserved postprandial appetite responses and precocious postprandial fullness, which seem to be associated with disturbances in gastrointestinal transit of the ingested meal and are likely to be independent of vagal fiber integrity or stomach-released ghrelin.
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Affiliation(s)
- Mayra M Kamiji
- Department of Medicine, Faculty of Medicine, University of São Paulo, Ribeirão Preto, SP, Brazil.
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Larrad Biliopancreatic Diversion in Sprague-Dawley Rats. Analysis of Weight Loss Related to Food Intake. Obes Surg 2008. [DOI: 10.1007/s11695-008-9735-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Mendieta-Zerón H, Larrad-Jiménez Á, Frühbeck G, Da Boit K, Diéguez C. Larrad Biliopancreatic Diversion in Sprague-Dawley Rats. Analysis of Weight Loss Related to Food Intake. Obes Surg 2008; 19:484-9. [DOI: 10.1007/s11695-008-9710-9] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2008] [Accepted: 09/11/2008] [Indexed: 11/29/2022]
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