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Müller TD, Adriaenssens A, Ahrén B, Blüher M, Birkenfeld AL, Campbell JE, Coghlan MP, D'Alessio D, Deacon CF, DelPrato S, Douros JD, Drucker DJ, Figueredo Burgos NS, Flatt PR, Finan B, Gimeno RE, Gribble FM, Hayes MR, Hölscher C, Holst JJ, Knerr PJ, Knop FK, Kusminski CM, Liskiewicz A, Mabilleau G, Mowery SA, Nauck MA, Novikoff A, Reimann F, Roberts AG, Rosenkilde MM, Samms RJ, Scherer PE, Seeley RJ, Sloop KW, Wolfrum C, Wootten D, DiMarchi RD, Tschöp MH. Glucose-dependent insulinotropic polypeptide (GIP). Mol Metab 2025; 95:102118. [PMID: 40024571 PMCID: PMC11931254 DOI: 10.1016/j.molmet.2025.102118] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/06/2024] [Revised: 02/06/2025] [Accepted: 02/24/2025] [Indexed: 03/04/2025] Open
Abstract
BACKGROUND Glucose-dependent insulinotropic polypeptide (GIP) was the first incretin identified and plays an essential role in the maintenance of glucose tolerance in healthy humans. Until recently GIP had not been developed as a therapeutic and thus has been overshadowed by the other incretin, glucagon-like peptide 1 (GLP-1), which is the basis for several successful drugs to treat diabetes and obesity. However, there has been a rekindling of interest in GIP biology in recent years, in great part due to pharmacology demonstrating that both GIPR agonism and antagonism may be beneficial in treating obesity and diabetes. This apparent paradox has reinvigorated the field, led to new lines of investigation, and deeper understanding of GIP. SCOPE OF REVIEW In this review, we provide a detailed overview on the multifaceted nature of GIP biology and discuss the therapeutic implications of GIPR signal modification on various diseases. MAJOR CONCLUSIONS Following its classification as an incretin hormone, GIP has emerged as a pleiotropic hormone with a variety of metabolic effects outside the endocrine pancreas. The numerous beneficial effects of GIPR signal modification render the peptide an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, drug-induced nausea and both bone and neurodegenerative disorders.
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Affiliation(s)
- Timo D Müller
- Institute for Diabetes and Obesity, Helmholtz Munich, Germany; German Center for Diabetes Research, DZD, Germany; Walther-Straub Institute for Pharmacology and Toxicology, Ludwig-Maximilians-University Munich (LMU), Germany.
| | - Alice Adriaenssens
- Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology, and Pharmacology, University College London, London, UK
| | - Bo Ahrén
- Department of Clinical Sciences, Lund, Lund University, Lund, Sweden
| | - Matthias Blüher
- Medical Department III-Endocrinology, Nephrology, Rheumatology, University of Leipzig Medical Center, Leipzig, Germany; Helmholtz Institute for Metabolic, Obesity and Vascular Research (HI-MAG) of the Helmholtz Zentrum München at the University of Leipzig and University Hospital Leipzig, Leipzig, Germany
| | - Andreas L Birkenfeld
- Department of Internal Medicine IV, University Hospital Tübingen, Tübingen 72076, Germany; Institute of Diabetes Research and Metabolic Diseases of the Helmholtz Centre Munich, Tübingen, Germany; German Center for Diabetes Research, Neuherberg, Germany
| | - Jonathan E Campbell
- Duke Molecular Physiology Institute, Duke University, Durham, NC, USA; Department of Medicine, Division of Endocrinology, Duke University, Durham, NC, USA; Department of Pharmacology and Cancer Biology, Duke University, Durham, NC, USA
| | - Matthew P Coghlan
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
| | - David D'Alessio
- Department of Medicine, Division of Endocrinology, Duke University, Durham, NC, USA; Duke Molecular Physiology Institute, Duke University, Durham, NC, USA
| | - Carolyn F Deacon
- School of Biomedical Sciences, Ulster University, Coleraine, UK; Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Stefano DelPrato
- Interdisciplinary Research Center "Health Science", Sant'Anna School of Advanced Studies, Pisa, Italy
| | | | - Daniel J Drucker
- The Lunenfeld-Tanenbaum Research Institute, Mt. Sinai Hospital, and the Department of Medicine, University of Toronto, Toronto, Ontario, Canada
| | - Natalie S Figueredo Burgos
- Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology, and Pharmacology, University College London, London, UK
| | - Peter R Flatt
- Diabetes Research Centre, School of Biomedical Sciences, Ulster University, Coleraine, Northern Ireland BT52 1SA, UK
| | - Brian Finan
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
| | - Ruth E Gimeno
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
| | - Fiona M Gribble
- Institute of Metabolic Science-Metabolic Research Laboratories & MRC-Metabolic Diseases Unit, University of Cambridge, Cambridge, UK
| | - Matthew R Hayes
- Department of Biobehavioral Health Sciences, School of Nursing, University of Pennsylvania, Philadelphia, PA, USA; Department of Psychiatry, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA
| | - Christian Hölscher
- Neurodegeneration Research Group, Henan Academy of Innovations in Medical Science, Xinzheng, China
| | - Jens J Holst
- Department of Biomedical Sciences and the Novo Nordisk Foundation Centre for Basic Metabolic Research, University of Copenhagen, Copenhagen, Denmark
| | - Patrick J Knerr
- Indianapolis Biosciences Research Institute, Indianapolis, IN, USA
| | - Filip K Knop
- Center for Clinical Metabolic Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark; Clinical Research, Steno Diabetes Center Copenhagen, Herlev, Denmark; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Christine M Kusminski
- Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Arkadiusz Liskiewicz
- Institute for Diabetes and Obesity, Helmholtz Munich, Germany; German Center for Diabetes Research, DZD, Germany; Department of Physiology, Faculty of Medical Sciences in Katowice, Medical University of Silesia, Katowice, Poland
| | - Guillaume Mabilleau
- Univ Angers, Nantes Université, ONIRIS, Inserm, RMeS UMR 1229, Angers, France; CHU Angers, Departement de Pathologie Cellulaire et Tissulaire, Angers, France
| | | | - Michael A Nauck
- Diabetes, Endocrinology and Metabolism Section, Department of Internal Medicine I, St. Josef-Hospital, Ruhr-University Bochum, Bochum, Germany
| | - Aaron Novikoff
- Institute for Diabetes and Obesity, Helmholtz Munich, Germany; German Center for Diabetes Research, DZD, Germany
| | - Frank Reimann
- Institute of Metabolic Science-Metabolic Research Laboratories & MRC-Metabolic Diseases Unit, University of Cambridge, Cambridge, UK
| | - Anna G Roberts
- Centre for Cardiovascular and Metabolic Neuroscience, Department of Neuroscience, Physiology, and Pharmacology, University College London, London, UK
| | - Mette M Rosenkilde
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences University of Copenhagen, Copenhagen, Denmark
| | - Ricardo J Samms
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
| | - Philip E Scherer
- Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Randy J Seeley
- Department of Surgery, University of Michigan, Ann Arbor, MI, USA
| | - Kyle W Sloop
- Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
| | - Christian Wolfrum
- Institute of Food, Nutrition and Health, ETH Zurich, 8092, Schwerzenbach, Switzerland
| | - Denise Wootten
- Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia; ARC Centre for Cryo-electron Microscopy of Membrane Proteins, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, Australia
| | | | - Matthias H Tschöp
- Helmholtz Munich, Neuherberg, Germany; Division of Metabolic Diseases, Department of Medicine, Technical University of Munich, Munich, Germany
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Gala K, Ghusn W, Abu Dayyeh BK. Gut motility and hormone changes after bariatric procedures. Curr Opin Endocrinol Diabetes Obes 2024; 31:131-137. [PMID: 38533785 DOI: 10.1097/med.0000000000000860] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/28/2024]
Abstract
PURPOSE OF REVIEW Metabolic and bariatric surgery (MBS) and endoscopic bariatric therapies (EBT) are being increasingly utilized for the management of obesity. They work through multiple mechanisms, including restriction, malabsorption, and changes in the gastrointestinal hormonal and motility. RECENT FINDINGS Roux-en-Y gastric bypass (RYGB) and laparoscopic sleeve gastrectomy (LSG) cause decrease in leptin, increase in GLP-1 and PYY, and variable changes in ghrelin (generally thought to decrease). RYGB and LSG lead to rapid gastric emptying, increase in small bowel motility, and possible decrease in colonic motility. Endoscopic sleeve gastroplasty (ESG) causes decrease in leptin and increase in GLP-1, ghrelin, and PYY; and delayed gastric motility. SUMMARY Understanding mechanisms of action for MBS and EBT is critical for optimal care of patients and will help in further refinement of these interventions.
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Affiliation(s)
- Khushboo Gala
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
| | - Wissam Ghusn
- Department of Internal Medicine, Boston University Medical Center, Boston, Massachusetts, USA
| | - Barham K Abu Dayyeh
- Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota
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Holst JJ, Madsbad S, Bojsen-Møller KN, Dirksen C, Svane M. New Lessons from the gut: Studies of the role of gut peptides in weight loss and diabetes resolution after gastric bypass and sleeve gastrectomy. Peptides 2024; 176:171199. [PMID: 38552903 DOI: 10.1016/j.peptides.2024.171199] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2024] [Revised: 03/18/2024] [Accepted: 03/22/2024] [Indexed: 04/05/2024]
Abstract
It has been known since 2005 that the secretion of several gut hormones changes radically after gastric bypass operations and, although more moderately, after sleeve gastrectomy but not after gastric banding. It has therefore been speculated that increased secretion of particularly GLP-1 and Peptide YY (PYY), which both inhibit appetite and food intake, may be involved in the weight loss effects of surgery and for improvements in glucose tolerance. Experiments involving inhibition of hormone secretion with somatostatin, blockade of their actions with antagonists, or blockade of hormone formation/activation support this notion. However, differences between results of bypass and sleeve operations indicate that distinct mechanisms may also be involved. Although the reductions in ghrelin secretion after sleeve gastrectomy would seem to provide an obvious explanation, experiments with restoration of ghrelin levels pointed towards effects on insulin secretion and glucose tolerance rather than on food intake. It seems clear that changes in GLP-1 secretion are important for insulin secretion after bypass and appear to be responsible for postbariatric hypoglycemia in glucose-tolerant individuals; however, with time the improvements in insulin sensitivity, which in turn are secondary to the weight loss, may be more important. Changes in bile acid metabolism do not seem to be of particular importance in humans.
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Affiliation(s)
- Jens Juul Holst
- The NovoNordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health Sciences, University of Copenhagen, Denmark.
| | - Sten Madsbad
- Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark
| | | | - Carsten Dirksen
- Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark
| | - Maria Svane
- Department of Endocrinology, Hvidovre Hospital, University of Copenhagen, Denmark
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Li S, Zhu H, Chen JDZ. Intestinal Electrical Stimulation Synchronized With Intestinal Slow Wave Ameliorates Glucagon-Induced Hyperglycemia in Rats. Neuromodulation 2024; 27:312-320. [PMID: 37897473 DOI: 10.1016/j.neurom.2023.10.001] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 09/26/2023] [Accepted: 10/03/2023] [Indexed: 10/30/2023]
Abstract
BACKGROUND Synchronized intestinal electrical stimulation (SIES), in which intestinal electrical stimulation (IES) is delivered in synchronization with the intrinsic slow wave of small intestine, was previously reported to be more potent in accelerating small intestine transit than IES delivered at fixed frequency and phase. We hypothesized that SIES is more potent in suppressing postprandial blood glucose by enhancing the release of glucagon-like peptide-1 (GLP-1) and insulin. MATERIALS AND METHODS Rats underwent long-term implant of two pairs of electrodes at the duodenum for IES and SIES, respectively. Acute hyperglycemia was induced with glucagon, and the oral glucose tolerance test was performed on separate days with IES, SIES, or sham (no stimulation). RESULTS 1. Glucagon reduced the percentage of normal slow wave in sham (70.9% ± 4.1%) from (84.9% ± 2.6%, p = 0.006) of control, which was ameliorated by SIES (82.5% ± 3.3%, p = 0.031). 2. IES and SIES reduced glucagon-induced increase of blood glucose (192 mg/dl) at 30 minutes by 17% and 20%, respectively. SIES showed a further inhibitory effect at 60 minutes (147 vs 171 mg/dl, p = 0.003, vs sham). 3. Compared with sham (139 pg/ml), GLP-1 at 30 minutes was increased in both IES (158 pg/ml) and SIES (169 pg/ml). GLP-1 level was still high at 60 minutes in rats with SIES. 4. At 30 minutes, the plasma insulin level was increased by 18.8 μIU/ml with SIES, which was significantly higher than that with sham (7.1 μIU/ml, p < 0.001) and IES (13.2 μIU/ml, p = 0.041). CONCLUSION SIES is more effective than IES in reducing glucagon-induced acute hyperglycemia by enhancing the release of GLP-1 and insulin.
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Affiliation(s)
- Shiying Li
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, USA
| | - Hongbing Zhu
- Transtimulation Research Inc, Oklahoma City, OK, USA
| | - Jiande D Z Chen
- Division of Gastroenterology and Hepatology, University of Michigan School of Medicine, Ann Arbor, MI, USA.
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Yin M, Wang Y, Han M, Liang R, Li S, Wang G, Gang X. Mechanisms of bariatric surgery for weight loss and diabetes remission. J Diabetes 2023; 15:736-752. [PMID: 37442561 PMCID: PMC10509523 DOI: 10.1111/1753-0407.13443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/12/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Obesity and type 2 diabetes(T2D) lead to defects in intestinal hormones secretion, abnormalities in the composition of bile acids (BAs), increased systemic and adipose tissue inflammation, defects of branched-chain amino acids (BCAAs) catabolism, and dysbiosis of gut microbiota. Bariatric surgery (BS) has been shown to be highly effective in the treatment of obesity and T2D, which allows us to view BS not simply as weight-loss surgery but as a means of alleviating obesity and its comorbidities, especially T2D. In recent years, accumulating studies have focused on the mechanisms of BS to find out which metabolic parameters are affected by BS through which pathways, such as which hormones and inflammatory processes are altered. The literatures are saturated with the role of intestinal hormones and the gut-brain axis formed by their interaction with neural networks in the remission of obesity and T2D following BS. In addition, BAs, gut microbiota and other factors are also involved in these benefits after BS. The interaction of these factors makes the mechanisms of metabolic improvement induced by BS more complicated. To date, we do not fully understand the exact mechanisms of the metabolic alterations induced by BS and its impact on the disease process of T2D itself. This review summarizes the changes of intestinal hormones, BAs, BCAAs, gut microbiota, signaling proteins, growth differentiation factor 15, exosomes, adipose tissue, brain function, and food preferences after BS, so as to fully understand the actual working mechanisms of BS and provide nonsurgical therapeutic strategies for obesity and T2D.
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Affiliation(s)
- Mengsha Yin
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Yao Wang
- Department of OrthopedicsThe Second Hospital Jilin UniversityChangchunChina
| | - Mingyue Han
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Ruishuang Liang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Shanshan Li
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Guixia Wang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Xiaokun Gang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
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Aukan MI, Skårvold S, Brandsaeter IØ, Rehfeld JF, Holst JJ, Nymo S, Coutinho S, Martins C. Gastrointestinal hormones and appetite ratings after weight loss induced by diet or bariatric surgery. Obesity (Silver Spring) 2023; 31:399-411. [PMID: 36536482 PMCID: PMC10108040 DOI: 10.1002/oby.23655] [Citation(s) in RCA: 15] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 11/08/2022] [Accepted: 11/10/2022] [Indexed: 12/24/2022]
Abstract
OBJECTIVE The aim of this study was to compare changes in gastrointestinal hormones and appetite ratings after a similar weight loss induced by a very low-energy diet alone or in combination with sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB). METHODS Patients with severe obesity scheduled for SG (n = 15) and RYGB (n = 14) and 15 controls (very low-energy diet alone) were recruited. Body weight/composition, plasma concentrations of ß-hydroxybutyric acid, acylated ghrelin, total glucagon-like peptide-1, total peptide YY, cholecystokinin, and ratings of hunger, fullness, desire to eat, and prospective food consumption were measured pre- and postprandially, before and after 10 weeks of intervention. RESULTS Changes in body weight/composition and level of ketosis were similar across groups. In SG and RYGB, basal and postprandial acylated ghrelin declined, and postprandial glucagon-like peptide-1 increased, both significantly more compared with controls. Postprandial peptide YY increased in all groups. Overall, postprandial hunger decreased, and postprandial fullness increased. But ratings of desire to eat and prospective food consumption were more favorable after both surgeries compared with controls. CONCLUSIONS Weight loss with SG and RYGB leads to more favorable changes in gastrointestinal hormones compared with diet alone, although ratings of appetite were reduced across all groups.
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Affiliation(s)
- Marthe Isaksen Aukan
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Centre of Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
| | - Silje Skårvold
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Ingrid Øfsti Brandsaeter
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
| | - Jens Frederik Rehfeld
- Department of Clinical Biochemistry, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
| | - Jens Juul Holst
- The NovoNordisk Center for Basic Metabolic Research and Department of Biomedical Sciences, The Panum Institute, University of Copenhagen, Copenhagen, Denmark
| | - Siren Nymo
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Centre of Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
- Nord-Trøndelag Hospital Trust, Clinic of Surgery, Namsos Hospital, Namsos, Norway
| | - Silvia Coutinho
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Department of Public Health Nutrition at the Institute of Basic Medical Sciences, Faculty of Medicine, University of Oslo, Oslo, Norway
| | - Catia Martins
- Obesity Research Group, Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology (NTNU), Trondheim, Norway
- Centre of Obesity and Innovation (ObeCe), Clinic of Surgery, St. Olav University Hospital, Trondheim, Norway
- Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama, USA
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Feris F, McRae A, Kellogg TA, McKenzie T, Ghanem O, Acosta A. Mucosal and hormonal adaptations after Roux-en-Y gastric bypass. Surg Obes Relat Dis 2023; 19:37-49. [PMID: 36243547 PMCID: PMC9797451 DOI: 10.1016/j.soard.2022.08.020] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 08/26/2022] [Accepted: 08/30/2022] [Indexed: 01/12/2023]
Abstract
The aim of this study was to perform a comprehensive literature review regarding the relevant hormonal and histologic changes observed after Roux-en-Y gastric bypass (RYGB). We aimed to describe the relevant hormonal (glucagon-like peptides 1 and 2 [GLP-1 and GLP-2], peptide YY [PYY], oxyntomodulin [OXM], bile acids [BA], cholecystokinin [CCK], ghrelin, glucagon, gastric inhibitory polypeptide [GIP], and amylin) profiles, as well as the histologic (mucosal cellular) adaptations happening after patients undergo RYGB. Our review compiles the current evidence and furthers the understanding of the rationale behind the food intake regulatory adaptations occurring after RYGB surgery. We identify gaps in the literature where the potential for future investigations and therapeutics may lie. We performed a comprehensive database search without language restrictions looking for RYGB bariatric surgery outcomes in patients with pre- and postoperative blood work hormonal profiling and/or gut mucosal biopsies. We gathered the relevant study results and describe them in this review. Where human findings were lacking, we included animal model studies. The amalgamation of physiologic, metabolic, and cellular adaptations following RYGB is yet to be fully characterized. This constitutes a fundamental aspiration for enhancing and individualizing obesity therapy.
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Affiliation(s)
- Fauzi Feris
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Alison McRae
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota
| | - Todd A Kellogg
- Division of Endocrine and Metabolic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Travis McKenzie
- Division of Endocrine and Metabolic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Omar Ghanem
- Division of Endocrine and Metabolic Surgery, Department of Surgery, Mayo Clinic, Rochester, Minnesota
| | - Andres Acosta
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, Rochester, Minnesota.
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Kodra N, Khella R, Nudelman BG, Dawkins B. Oral Potassium Malabsorption Following Bariatric Surgery. Cureus 2022; 14:e28607. [PMID: 36213722 PMCID: PMC9529024 DOI: 10.7759/cureus.28607] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/30/2022] [Indexed: 11/06/2022] Open
Abstract
Bariatric surgery is one of the most effective long-term solutions for treating obesity due to its sustained weight loss and reduction of obesity-related comorbidities. However, nutritional deficiencies are common due to the alteration of the anatomy and physiology of the gastrointestinal tract. These include the malabsorption of macronutrients, vitamins, minerals, trace elements, and drugs. In this report, we present the case of a female patient who underwent Roux-en-Y gastric bypass surgery and subsequently developed exclusive potassium malabsorption refractory to oral replenishment.
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Guerrero-Hreins E, Foldi CJ, Oldfield BJ, Stefanidis A, Sumithran P, Brown RM. Gut-brain mechanisms underlying changes in disordered eating behaviour after bariatric surgery: a review. Rev Endocr Metab Disord 2022; 23:733-751. [PMID: 34851508 DOI: 10.1007/s11154-021-09696-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 11/12/2021] [Indexed: 02/07/2023]
Abstract
Bariatric surgery results in long-term weight loss and an improved metabolic phenotype due to changes in the gut-brain axis regulating appetite and glycaemia. Neuroendocrine alterations associated with bariatric surgery may also influence hedonic aspects of eating by inducing changes in taste preferences and central reward reactivity towards palatable food. However, the impact of bariatric surgery on disordered eating behaviours (e.g.: binge eating, loss-of-control eating, emotional eating and 'addictive eating'), which are commonly present in people with obesity are not well understood. Increasing evidence suggests gut-derived signals, such as appetitive hormones, bile acid profiles, microbiota concentrations and associated neuromodulatory metabolites, can influence pathways in the brain implicated in food intake, including brain areas involved in sensorimotor, reward-motivational, emotional-arousal and executive control components of food intake. As disordered eating prevalence is a key mediator of weight-loss success and patient well-being after bariatric surgery, understanding how changes in the gut-brain axis contribute to disordered eating incidence and severity after bariatric surgery is crucial to better improve treatment outcomes in people with obesity.
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Affiliation(s)
- Eva Guerrero-Hreins
- Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Melbourne, Australia
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Melbourne, Australia
| | - Claire J Foldi
- Department of Physiology, Monash University, Clayton, Melbourne, Australia
- Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Australia
| | - Brian J Oldfield
- Department of Physiology, Monash University, Clayton, Melbourne, Australia
- Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Australia
| | - Aneta Stefanidis
- Department of Physiology, Monash University, Clayton, Melbourne, Australia
- Biomedicine Discovery Institute, Monash University, Clayton, Melbourne, Australia
| | - Priya Sumithran
- Department of Medicine (St Vincent's), University of Melbourne, Melbourne, Australia
- Department of Endocrinology, Austin Health, Melbourne, Australia
| | - Robyn M Brown
- Department of Biochemistry and Pharmacology, University of Melbourne, Parkville, Melbourne, Australia.
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Melbourne, Australia.
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Lunger F, Aeschbacher P, Nett PC, Peros G. The impact of bariatric and metabolic surgery on cancer development. Front Surg 2022; 9:918272. [PMID: 35910464 PMCID: PMC9334768 DOI: 10.3389/fsurg.2022.918272] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/12/2022] [Accepted: 06/30/2022] [Indexed: 12/21/2022] Open
Abstract
Obesity (BMI ≥ 30 kg/m2) with related comorbidities such as type 2 diabetes mellitus, cardiovascular disease, sleep apnea syndrome, and fatty liver disease is one of the most common preventable risk factors for cancer development worldwide. They are responsible for at least 40% of all newly diagnosed cancers, including colon, ovarian, uterine, breast, pancreatic, and esophageal cancer. Although various efforts are being made to reduce the incidence of obesity, its prevalence continues to spread in the Western world. Weight loss therapies such as lifestyle change, diets, drug therapies (GLP-1-receptor agonists) as well as bariatric and metabolic surgery are associated with an overall risk reduction of cancer. Therefore, these strategies should always be essential in therapeutical concepts in obese patients. This review discusses pre- and post-interventional aspects of bariatric and metabolic surgery and its potential benefit on cancer development in obese patients.
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Affiliation(s)
- Fabian Lunger
- Department for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
- Department of Visceral and Thoracic Surgery, Cantonal Hospital of Winterthur, Winterthur, Switzerland
| | - Pauline Aeschbacher
- Department for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
| | - Philipp C. Nett
- Department for Visceral Surgery and Medicine, Bern University Hospital, University of Bern, Bern, Switzerland
- Correspondance: Philipp C. Nett
| | - Georgios Peros
- Department of Visceral and Thoracic Surgery, Cantonal Hospital of Winterthur, Winterthur, Switzerland
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11
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Estabile PC, Almeida MCD, Campagnoli EB, Santo MA, Rodrigues MRDS, Milléo FQ, Artoni RF. IMMUNOHISTOCHEMICAL DETECTION OF L CELLS IN GASTROINTESTINAL TRACT MUCOSA OF PATIENTS AFTER SURGICAL TREATMENT FOR CONTROL OF TYPE 2 DIABETES MELLITUS. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2022; 35:e1651. [PMID: 35730880 PMCID: PMC9254391 DOI: 10.1590/0102-672020210002e1651] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Accepted: 01/18/2022] [Indexed: 06/15/2023]
Abstract
OBJECTIVE Type 2 diabetes mellitus (T2DM) is a disease of global impact that has led to an increase in comorbidities and mortality in several countries. Immunoexpression of the incretin hormones such as glucagon-like peptide-1 (GLP-1) and peptide YY (3-36) (PYY3-36) can be used as a scorer in the gastrointestinal tract to analyze L-cell activity in response to T2DM treatment. This study aimed to investigate the presence, location, and secretion of L cells in the small intestine of patients undergoing the form of bariatric surgery denominated adaptive gastroenteromentectomy with partial bipartition. METHODS Immunohistochemical assays, quantitative real-time polymerase chain reaction (qPCR), and Western blot analysis were performed on samples of intestinal mucosa from patients with T2DM in both the preoperative and postoperative periods. RESULTS All results were consistent and indicated basal expression and secretion of GLP-1 and PYY3-36 incretins by L cells. A greater density of cells was demonstrated in the most distal portions of the small intestine. No significant difference was found between GLP-1 and PYY3-36 expression levels in the preoperative and postoperative periods because of prolonged fasting during which the samples were collected. CONCLUSION The greater number of L cells in activity implies better peptide signaling, response, and functioning of the neuroendocrine system.
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Affiliation(s)
- Priscila Costa Estabile
- Postgraduate Program in Science in Gastroenterology, University of São Paulo, São Paulo, SP, Brazil
| | - Mara Cristina de Almeida
- Department of Structural, Molecular and Genetics Biology, State University of Ponta Grossa, Ponta Grossa, PR, Brazil
| | | | - Marco Aurelio Santo
- Associate Professor at University of São Paulo School of Medicine, is Director of Bariatric and Metabolic Surgery Unit at Hospital das Clinicas, Brazil
| | | | | | - Roberto Ferreira Artoni
- Department of Structural, Molecular and Genetics Biology, State University of Ponta Grossa, Ponta Grossa, PR, Brazil
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12
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Appetite Changes in Weight Regain and Weight Maintenance After Roux-en-Y Gastric Bypass. Obes Surg 2022; 32:1-12. [PMID: 35441332 DOI: 10.1007/s11695-022-06061-5] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2022] [Revised: 04/11/2022] [Accepted: 04/13/2022] [Indexed: 10/18/2022]
Abstract
PURPOSE Roux-en-Y gastric bypass (RYGB) surgery produces significant weight loss. However, a number of patients experience weight regain years after surgery. Factors driving weight regain after surgical interventions are currently being explored. Our objective was to investigate appetite-related measures associated with weight regain after RYGB surgery. MATERIALS AND METHODS Using a cross-sectional design, 29 participants (49.6 ± 9.1 years of age; current BMI 32.4 ± 4.7 kg/m2, 43.6 ± 8.9 months post-RYGB) were stratified into tertiles according to weight regain per month after nadir (weight maintenance (WM), n = 9; low weight regain (LWR), n = 10; and high weight regain (HWR), n = 10). The average weight regain was, by design, significantly different between the groups (WM = 2.2 ± 2.5 kg; LWR = 10.0 ± 3.4 kg; HWR = 14.9 ± 6.3 kg regained, p < 0.05). Appetite (visual analog scales), olfactory performance ("sniffin sticks"), eating behaviors (Three Factor Eating Questionnaire), food reward (Leeds Food Preference Questionnaire), and appetite-related hormones (ghrelin, PYY, GLP-1 and leptin) were measured fasting and in response to a standardized test meal. RESULTS Dietary restraint was significantly higher than clinical cutoffs in WM and LWR (p < 0.05). As expected, significant time effects were noted for ghrelin, PYY, and GLP-1, but there were no group differences. CONCLUSION The results suggest that appetite-related outcomes are similar across individuals who have maintained weight loss and experienced regain following RYGB.
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13
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Enteroendocrine System and Gut Barrier in Metabolic Disorders. Int J Mol Sci 2022; 23:ijms23073732. [PMID: 35409092 PMCID: PMC8998765 DOI: 10.3390/ijms23073732] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2022] [Revised: 03/25/2022] [Accepted: 03/26/2022] [Indexed: 02/06/2023] Open
Abstract
With the continuous rise in the worldwide prevalence of obesity and type 2 diabetes, developing therapies regulating body weight and glycemia has become a matter of great concern. Among the current treatments, evidence now shows that the use of intestinal hormone analogs (e.g., GLP1 analogs and others) helps to control glycemia and reduces body weight. Indeed, intestinal endocrine cells produce a large variety of hormones regulating metabolism, including appetite, digestion, and glucose homeostasis. Herein, we discuss how the enteroendocrine system is affected by local environmental and metabolic signals. These signals include those arising from unbalanced diet, gut microbiota, and the host metabolic organs and their complex cross-talk with the intestinal barrier integrity.
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14
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Martinou E, Stefanova I, Iosif E, Angelidi AM. Neurohormonal Changes in the Gut-Brain Axis and Underlying Neuroendocrine Mechanisms following Bariatric Surgery. Int J Mol Sci 2022; 23:3339. [PMID: 35328759 PMCID: PMC8954280 DOI: 10.3390/ijms23063339] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 02/05/2023] Open
Abstract
Obesity is a complex, multifactorial disease that is a major public health issue worldwide. Currently approved anti-obesity medications and lifestyle interventions lack the efficacy and durability needed to combat obesity, especially in individuals with more severe forms or coexisting metabolic disorders, such as poorly controlled type 2 diabetes. Bariatric surgery is considered an effective therapeutic modality with sustained weight loss and metabolic benefits. Numerous genetic and environmental factors have been associated with the pathogenesis of obesity, while cumulative evidence has highlighted the gut-brain axis as a complex bidirectional communication axis that plays a crucial role in energy homeostasis. This has led to increased research on the roles of neuroendocrine signaling pathways and various gastrointestinal peptides as key mediators of the beneficial effects following weight-loss surgery. The accumulate evidence suggests that the development of gut-peptide-based agents can mimic the effects of bariatric surgery and thus is a highly promising treatment strategy that could be explored in future research. This article aims to elucidate the potential underlying neuroendocrine mechanisms of the gut-brain axis and comprehensively review the observed changes of gut hormones associated with bariatric surgery. Moreover, the emerging role of post-bariatric gut microbiota modulation is briefly discussed.
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Affiliation(s)
- Eirini Martinou
- Department of Upper Gastrointestinal Surgery, Frimley Health NHS Foundation Trust, Camberley GU16 7UJ, UK;
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
| | - Irena Stefanova
- Department of General Surgery, Frimley Health NHS Foundation Trust, Camberley GU16 7UJ, UK;
| | - Evangelia Iosif
- Department of General Surgery, Royal Surrey County Hospital, Guildford GU2 7XX, UK;
| | - Angeliki M. Angelidi
- Division of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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15
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Roux-en-Y Gastric Bypass and Caloric Restriction but Not Gut Hormone-Based Treatments Profoundly Impact the Hypothalamic Transcriptome in Obese Rats. Nutrients 2021; 14:nu14010116. [PMID: 35010991 PMCID: PMC8746874 DOI: 10.3390/nu14010116] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 12/23/2021] [Accepted: 12/24/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND The hypothalamus is an important brain region for the regulation of energy balance. Roux-en-Y gastric bypass (RYGB) surgery and gut hormone-based treatments are known to reduce body weight, but their effects on hypothalamic gene expression and signaling pathways are poorly studied. METHODS Diet-induced obese male Wistar rats were randomized into the following groups: RYGB, sham operation, sham + body weight-matched (BWM) to the RYGB group, osmotic minipump delivering PYY3-36 (0.1 mg/kg/day), liraglutide s.c. (0.4 mg/kg/day), PYY3-36 + liraglutide, and saline. All groups (except BWM) were kept on a free choice of high- and low-fat diets. Four weeks after interventions, hypothalami were collected for RNA sequencing. RESULTS While rats in the RYGB, BWM, and PYY3-36 + liraglutide groups had comparable reductions in body weight, only RYGB and BWM treatment had a major impact on hypothalamic gene expression. In these groups, hypothalamic leptin receptor expression as well as the JAK-STAT, PI3K-Akt, and AMPK signaling pathways were upregulated. No significant changes could be detected in PYY3-36 + liraglutide-, liraglutide-, and PYY-treated groups. CONCLUSIONS Despite causing similar body weight changes compared to RYGB and BWM, PYY3-36 + liraglutide treatment does not impact hypothalamic gene expression. Whether this striking difference is favorable or unfavorable to metabolic health in the long term requires further investigation.
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Metabolic profiles, energy expenditures, and body compositions of the weight regain versus sustained weight loss patients who underwent Roux-en-Y gastric bypass. Surg Obes Relat Dis 2021; 17:2015-2025. [PMID: 34635422 DOI: 10.1016/j.soard.2021.09.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Revised: 08/11/2021] [Accepted: 09/06/2021] [Indexed: 01/02/2023]
Abstract
BACKGROUND Weight regain (WR) has been an emerging problem after Roux-en Y gastric bypass (RYGB) and little is known about the mechanisms of WR after RYGB. OBJECTIVE To evaluate the mechanisms of WR after RYGB through the postprandial gut hormones response, particularly glucagon-like peptide-1 (GLP-1), which regulates appetite control, energy expenditure, body composition, physical activities, dietary intake, and psychological factors. SETTING Duke University Medical Center, Durham, North Carolina. METHODS A cross sectional study of 34 patients who underwent RYGB at least 2 years and achieved ≥50% of excess weight loss at 1year was conducted. The subjects were categorized into WR group or sustained weight loss group, based upon whether their WR was ≥15% of postoperative lowest weight. RESULTS The WR group had less augmented postprandial GLP-1 response but exaggerated hyperinsulinemia. Postprandial peptide YY, ghrelin, and glucose were not different between group. Patients who regained weight required less weight-adjusted energy expenditure and had more percentage body fat and less percentage lean mass. The caloric intake and diet composition were comparable between groups; however, the WR group had higher depression scores, binge eating scales, and hunger rating and spent significantly less time on vigorous exercise. CONCLUSIONS The mechanisms of WR in patients who were initially successful after RYGB are complex and involved not only the role of postprandial gut hormone response but are also related to energy expenditure adaptation and body composition changes. Moreover, food preference and physical activity may play roles in weight control after bariatric surgery. Further prospective controlled trial is needed to explore the mechanisms of WR.
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17
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Smith KR, Moran TH. Gastrointestinal peptides in eating-related disorders. Physiol Behav 2021; 238:113456. [PMID: 33989649 PMCID: PMC8462672 DOI: 10.1016/j.physbeh.2021.113456] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2020] [Revised: 04/19/2021] [Accepted: 05/04/2021] [Indexed: 12/13/2022]
Abstract
Food intake is tightly controlled by homeostatic signals sensitive to metabolic need for the regulation of body weight. This review focuses on the peripherally-secreted gastrointestinal peptides (i.e., ghrelin, cholecystokinin, glucagon-like peptide 1, and peptide tyrosine tyrosine) that contribute to the control of appetite and discusses how these peptides or the signals arising from their release are disrupted in eating-related disorders across the weight spectrum, namely anorexia nervosa, bulimia nervosa, and obesity, and whether they are normalized following weight restoration or weight loss treatment. Further, the role of gut peptides in the pathogenesis and treatment response in human weight conditions as identified by rodent models are discussed. Lastly, we review the incretin- and hormone-based pharmacotherapies available for the treatment of obesity and eating-related disorders.
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Affiliation(s)
- Kimberly R Smith
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States.
| | - Timothy H Moran
- Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, United States
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18
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Xue H, Huang L, Tu J, Ding L, Huang W. Bile acids and metabolic surgery. LIVER RESEARCH 2021; 5:164-170. [PMID: 39957846 PMCID: PMC11791848 DOI: 10.1016/j.livres.2021.05.001] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2021] [Revised: 04/04/2021] [Accepted: 05/05/2021] [Indexed: 02/16/2023]
Abstract
The epidemic of obesity and its co-mortalities has reached an alarming level worldwide. Currently, metabolic surgeries, especially the Roux-en-Y gastric bypass and vertical sleeve gastrectomy, are the most effective and sustainable treatments for obesity, type 2 diabetes, non-alcoholic steatohepatitis, as well as other metabolic diseases. However, the invasive nature of the surgeries limits their broad applications to the general public. Therefore, developing alternative non-invasive approaches to mimic metabolic surgery is an important direction of the field. Recent studies have identified several potential metabolic surgery-induced downstream endocrine mediators, among which bile acids are key candidate signaling molecules. Bile acids are profoundly altered by metabolic surgery, which contributes to the metabolic effects of the surgery. In this review, we focus on the most recent studies on the roles of bile acids and bile acid receptors farnesoid X receptor and Takeda G protein-coupled receptor 5 in mediating the metabolic effects of metabolic surgery. We conclude that targeting bile acid pathways may be a promising pharmacological approach to mimic the beneficial effects of metabolic surgery.
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Affiliation(s)
- Hui Xue
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Luyao Huang
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Jui Tu
- Department of Diabetes Complications and Metabolism, Institute of Diabetes and Metabolism Research Center, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
| | - Lili Ding
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Wendong Huang
- Department of Diabetes Complications and Metabolism, Institute of Diabetes and Metabolism Research Center, Beckman Research Institute, City of Hope National Medical Center, Duarte, CA, USA
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19
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Mueller A, Palilla S, Carter J. Optimal Surgical Treatment for Type 2 Diabetes: Sleeve Gastrectomy or Gastric Bypass? Adv Surg 2021; 55:1-8. [PMID: 34389085 DOI: 10.1016/j.yasu.2021.05.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Affiliation(s)
- Amanda Mueller
- Department of Surgery, University of California - San Francisco, 513 Parnassus Avenue, HSW1601, San Francisco, CA 94143, USA
| | - Sarah Palilla
- Department of Surgery, University of California - San Francisco, 513 Parnassus Avenue, HSW1601, San Francisco, CA 94143, USA
| | - Jonathan Carter
- Department of Surgery, University of California - San Francisco, 513 Parnassus Avenue, HSW1601, San Francisco, CA 94143, USA.
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20
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Gastrointestinal quality of life before and short- and long-term after Roux-en-Y gastric bypass for severe obesity. Surg Obes Relat Dis 2021; 17:1583-1590. [PMID: 34099420 DOI: 10.1016/j.soard.2021.05.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/26/2021] [Accepted: 05/11/2021] [Indexed: 11/20/2022]
Abstract
BACKGROUND Overall quality of life (QoL) is generally improved after bariatric surgery. Gastrointestinal (GI) symptoms including abdominal pain have been reported in up to >30% of patients after Roux-en-Y gastric bypass (RYGB), and may negatively influence QoL, especially GI-QoL. OBJECTIVES To evaluate the evolution of GI symptoms and GI-QoL short- and long-term after RYGB. SETTING Two public hospitals METHODS: Candidates for bariatric surgery (n = 128, BMI = 44.2 ± 7.4) or patients who had undergone RYGB 2-4 years (n = 161, BMI = 29.3 ± 15.9) and 5-10 years (n = 121, BMI = 31.3 ± 6.5) before were invited to complete a questionnaire combining 3 validated questionnaires (GIQLI, GSRS, and PCS) specifically designed to evaluate GI-QoL. Scores were compared between the preoperative, early, and late postoperative periods. RESULTS The GIQLI score improved from 88.1 before surgery to 118.6 (P < .0001) and 109.7 (P < .0001) in the early and late postoperative periods respectively. GSRS score improved from 15.6 to 10.1 (P = .0001) and 12.8 (P = .012), and PCS-score improved from 19 to 4.5 (P = .0001) and 8.3 (P = .0001), respectively. The GI subscore of the GIQLI improved from 57.4 to 62.1 (P = .007) in the early period but was not significantly different in the late period (59.3 versus 57.4, P = .3). The psychological impact of GI symptoms decreased at both postoperative time points. CONCLUSION GI-QoL is markedly improved after RYGB, and this improvement persists up to 10 years. GI symptoms decrease early after surgery and do not worsen in the longer term. Their psychological impact is markedly reduced.
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21
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Käkelä P, Rantanen T, Virtanen KA. The Importance of Intestinal Length in Triglyceride Metabolism and in Predicting the Outcomes of Comorbidities in Laparoscopic Roux-en-Y Gastric Bypass-a Narrative Review. Obes Surg 2021; 31:3291-3295. [PMID: 33914241 PMCID: PMC8175306 DOI: 10.1007/s11695-021-05421-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Revised: 04/01/2021] [Accepted: 04/07/2021] [Indexed: 11/28/2022]
Abstract
In this narrative review, we will appraise if modification of the length of bypassed small intestine based on measured total small intestinal length could optimize the outcomes of the laparoscopic Roux-en-Y gastric bypass (LRYGB). We provide a summary of carefully selected studies to serve as examples and to draw tentative conclusions of the effects of LRYGB on remission of comorbidities. As the heterogeneity of the included studies varied in terms of outcomes, type of study, length of the bypassed small intestine, and the follow-up, a common endpoint could not be defined for this narrative article. To achieve efficient metabolic outcomes, it is important to carefully choose the small intestine length excluded from the food passage suited best to each individual patient. ![]()
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Affiliation(s)
- Pirjo Käkelä
- Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland.
| | - Tuomo Rantanen
- Department of Surgery, University of Eastern Finland and Kuopio University Hospital, Kuopio, Finland
| | - Kirsi A Virtanen
- Department of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Department of Endocrinology and Clinical Nutrition, Kuopio University Hospital, Kuopio, Finland
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22
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Theilade S, Christensen MB, Vilsbøll T, Knop FK. An overview of obesity mechanisms in humans: Endocrine regulation of food intake, eating behaviour and common determinants of body weight. Diabetes Obes Metab 2021; 23 Suppl 1:17-35. [PMID: 33621414 DOI: 10.1111/dom.14270] [Citation(s) in RCA: 27] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 11/21/2020] [Accepted: 11/23/2020] [Indexed: 12/13/2022]
Abstract
Obesity is one of the biggest health challenges of the 21st century, already affecting close to 700 million people worldwide, debilitating and shortening lives and costing billions of pounds in healthcare costs and loss of workability. Body weight homeostasis relies on complex biological mechanisms and the development of obesity occurs on a background of genetic susceptibility and an environment promoting increased caloric intake and reduced physical activity. The pathophysiology of common obesity links neuro-endocrine and metabolic disturbances with behavioural changes, genetics, epigenetics and cultural habits. Also, specific causes of obesity exist, including monogenetic diseases and iatrogenic causes. In this review, we provide an overview of obesity mechanisms in humans with a focus on energy homeostasis, endocrine regulation of food intake and eating behavior, as well as the most common specific causes of obesity.
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Affiliation(s)
- Simone Theilade
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Medicine, Herlev-Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Mikkel B Christensen
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Pharmacology, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
- Copenhagen Center for Translational Research, Bispebjerg Hospital, University of Copenhagen, Copenhagen, Denmark
| | - Tina Vilsbøll
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
| | - Filip K Knop
- Center for Clinical Metabolic Research, Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
- Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Medicine, Herlev-Gentofte Hospital, University of Copenhagen, Copenhagen, Denmark
- Steno Diabetes Center Copenhagen, Gentofte, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
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23
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Alaber O, Mansoor E, Perez LKM, Dumot J, Bhatt A, Chak A. High grade dysplasia or esophageal adenocarcinoma in patients with a history of Roux-en-Y gastric bypass surgery: a case series. Endoscopy 2021; 53:147-151. [PMID: 32663878 DOI: 10.1055/a-1203-5832] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) is the favored bariatric option in patients with gastroesophageal reflux and Barrett's esophagus because it prevents reflux. Weight loss and decreased reflux following RYGB could theoretically minimize the risk of progression to cancer. We aimed to demonstrate the management of high grade dysplasia (HGD) and esophageal adenocarcinoma (EAC) developing in patients after RYGB. METHODS A prospectively maintained database was searched to identify cases of HGD and cancer in RYGB patients. Charts were reviewed for past history, endoscopic findings, endoscopic therapy, and pathology findings. RESULTS There were five cases where HGD/EAC developed several years after RYGB. The prior bariatric surgery precluded curative esophagectomy, illustrating the management challenges. All but one of the patients were uniquely and successfully managed with endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD). CONCLUSIONS RYGB patients are still at risk of developing esophageal cancer. Patients at risk should be screened prior to RYGB and those with Barret's esophagus need to undergo rigorous endoscopic surveillance following surgery. If detected early, EMR and ESD are invaluable in managing those who progress.
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Affiliation(s)
- Omer Alaber
- Division of Gastroenterology and Liver Disease, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Emad Mansoor
- Division of Gastroenterology and Liver Disease, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | | | - John Dumot
- Division of Gastroenterology and Liver Disease, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
| | - Amit Bhatt
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Amitabh Chak
- Division of Gastroenterology and Liver Disease, University Hospitals Cleveland Medical Center, Case Western Reserve University, Cleveland, Ohio, USA
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Zhang C, Biehl Rudkjær LC, Cachón MF, Falkenhahn M, Theis S, Schmidt T, Vrang N, Jelsing J, Rigbolt K. Transcriptomic changes in pancreatic islets, adipose and liver after Roux-en-Y gastric bypass in a diet-induced obese rat model. Peptides 2021; 136:170467. [PMID: 33253774 DOI: 10.1016/j.peptides.2020.170467] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/27/2020] [Revised: 10/28/2020] [Accepted: 11/21/2020] [Indexed: 12/28/2022]
Abstract
Roux-en-Y gastric bypass (RYGB) is the most efficient intervention in morbid obesity and promotes metabolic improvements in several peripheral tissues. However, the underlying molecular mechanisms are still poorly understood. To further understand the effects of RYGB on peripheral tissues transcriptomes, we determined transcriptome signatures in pancreatic islets, adipose and liver tissue from diet-induced obese (DIO) rats model following RYGB. Whereas RYGB led to discrete gene expression changes in pancreatic islets, substantial transcriptome changes were observed in metabolic and immune signaling pathways in adipose tissue and the liver, indicating major gene adaptive responses in fat-storing tissues. Compared to RYGB DIO rats, peripheral tissue transcriptome signatures were markedly different in caloric restricted weight matching DIO rats, implying that caloric restriction paradigms do not reflect transcriptomic regulations of RYGB induced weight loss. The present gene expression study may serve as a basis for further investigations into molecular regulatory effects in peripheral tissues following RYGB-induced weight loss.
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Affiliation(s)
| | | | | | | | - Stefan Theis
- Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany
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25
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Intestinal Electrical Stimulation Enhances Release of Postprandial Incretin Hormones Via Cholinergic Mechanisms. Obes Surg 2021; 31:1957-1966. [PMID: 33469859 DOI: 10.1007/s11695-021-05228-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2020] [Revised: 01/05/2021] [Accepted: 01/08/2021] [Indexed: 10/22/2022]
Abstract
INTRODUCTION Intestinal electrical stimulation (IES) has been reported to reduce body weight and improve glucose tolerance in obese and diabetic rats. Our study aimed to investigate possible IES mechanisms involving incretin hormones using intraduodenal glucose infusion in rats. We hypothesized that the enhanced release of postprandial glucagon-like peptide-1 (GLP-1) at early phase by IES was mediated through neuro/paracrine mechanisms involving the vagal nerve and glucose-dependent insulinotropic peptide (GIP). METHODS Fifteen normal male Sprague-Dawley rats chronically implanted with duodenal electrodes for IES, and an intra-duodenum catheter for the infusion of glucose were studied in a series of sessions with IES of different parameters with and without atropine and M3 receptor antagonist. Blood samples were collected via the tail vein for the measurement of blood glucose, and plasma GLP-1, and GIP. RESULTS (1) Compared to sham-IES, IES of 0.3 ms reduced blood glucose by 16.5-28.4% between 30 and 120 min (all time points p < 0.05), and IES of 3-ms reduced blood glucose at 60 (12.6%) and 90 min (11.8%). IES of 0.3 ms showed a greater hypoglycemic effect than 3 ms (p = 0.024) at 30 min. (2) IES elevated plasma GLP-1 with 0.3 ms (p = 0.001) and with 3 ms p = 0.03). (3) IES substantially elevated plasma GIP with 0.3 ms (p = 0.002) and with 3 ms (p < 0.001). (4) Pretreatment of atropine and the M3 receptor antagonist 4-DAMP blocked the effects of IES on GLP-1, GIP, and blood glucose. CONCLUSIONS IES reduces postprandial blood glucose by enhancing the release of GLP-1 and GIP mediated via the cholinergic mechanism.
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Esquivel Zuniga R, DeBoer MD. Prediabetes in Adolescents: Prevalence, Management and Diabetes Prevention Strategies. Diabetes Metab Syndr Obes 2021; 14:4609-4619. [PMID: 34858039 PMCID: PMC8629936 DOI: 10.2147/dmso.s284401] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Accepted: 11/03/2021] [Indexed: 12/16/2022] Open
Abstract
The ongoing obesity epidemic in children and adolescents has greatly increased the prevalence of related comorbidities. Prediabetes is defined based on levels of fasting glucose, oral glucose tolerance tests or hemoglobin A1c, that are intermediate between normal levels and thresholds that define type 2 diabetes mellitus (T2DM). As such, prediabetes represents a sign of early pathophysiology preceding T2DM development. Recent analyses of data from US adolescents estimate prediabetes to be present in 4-23% of adolescents, depending on criteria used, with other studies finding an 8% risk of progression from prediabetes to T2DM over a 3-year period. These data support the importance of intervention to avoid long-term sequelae, focusing on reducing degree of obesity and insulin resistance. Lifestyle modification, with increases in physical activity and dietary improvements, remains the first-line approach. Other interventions are based on additional long-term risks and range from metformin treatment for more moderate cases of prediabetes to bariatric surgery for adolescents with severe obesity and comorbidities. As data accumulate regarding sequelae of T2DM in adolescents, there remains a critical need for prevention of obesity and T2DM throughout childhood, and prediabetes should be a trigger for improving this risk profile.
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Affiliation(s)
- Rebeca Esquivel Zuniga
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA
| | - Mark D DeBoer
- Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia, Charlottesville, VA, USA
- Correspondence: Mark D DeBoer Division of Pediatric Endocrinology, University of Virginia, PO Box 800386, Charlottesville, VA, 22903, USATel +1 434-924-5956Fax +1 434-924-9181 Email
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Koepsell H. Glucose transporters in the small intestine in health and disease. Pflugers Arch 2020; 472:1207-1248. [PMID: 32829466 PMCID: PMC7462918 DOI: 10.1007/s00424-020-02439-5] [Citation(s) in RCA: 148] [Impact Index Per Article: 29.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Revised: 07/11/2020] [Accepted: 07/17/2020] [Indexed: 12/23/2022]
Abstract
Absorption of monosaccharides is mainly mediated by Na+-D-glucose cotransporter SGLT1 and the facititative transporters GLUT2 and GLUT5. SGLT1 and GLUT2 are relevant for absorption of D-glucose and D-galactose while GLUT5 is relevant for D-fructose absorption. SGLT1 and GLUT5 are constantly localized in the brush border membrane (BBM) of enterocytes, whereas GLUT2 is localized in the basolateral membrane (BLM) or the BBM plus BLM at low and high luminal D-glucose concentrations, respectively. At high luminal D-glucose, the abundance SGLT1 in the BBM is increased. Hence, D-glucose absorption at low luminal glucose is mediated via SGLT1 in the BBM and GLUT2 in the BLM whereas high-capacity D-glucose absorption at high luminal glucose is mediated by SGLT1 plus GLUT2 in the BBM and GLUT2 in the BLM. The review describes functions and regulations of SGLT1, GLUT2, and GLUT5 in the small intestine including diurnal variations and carbohydrate-dependent regulations. Also, the roles of SGLT1 and GLUT2 for secretion of enterohormones are discussed. Furthermore, diseases are described that are caused by malfunctions of small intestinal monosaccharide transporters, such as glucose-galactose malabsorption, Fanconi syndrome, and fructose intolerance. Moreover, it is reported how diabetes, small intestinal inflammation, parental nutrition, bariatric surgery, and metformin treatment affect expression of monosaccharide transporters in the small intestine. Finally, food components that decrease D-glucose absorption and drugs in development that inhibit or downregulate SGLT1 in the small intestine are compiled. Models for regulations and combined functions of glucose transporters, and for interplay between D-fructose transport and metabolism, are discussed.
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Affiliation(s)
- Hermann Koepsell
- Institute for Anatomy and Cell Biology, University of Würzburg, Koellikerstr 6, 97070, Würzburg, Germany.
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Tuero C, Valenti V, Rotellar F, Landecho MF, Cienfuegos JA, Frühbeck G. Revisiting the Ghrelin Changes Following Bariatric and Metabolic Surgery. Obes Surg 2020; 30:2763-2780. [PMID: 32323063 DOI: 10.1007/s11695-020-04601-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Since the description of ghrelin in 1999, several studies have dug into the effects of this hormone and its relationship with bariatric surgery. While some aspects are still unresolved, a clear connection between ghrelin and the changes after metabolic surgery have been established. Besides weight loss, a significant amelioration in obesity-related comorbidities following surgery has also been reported. These changes in patients occur in the early postoperative period, before the weight loss appears, so that amelioration may be mainly due to hormonal changes. The purpose of this review is to go through the current body of knowledge of ghrelin's physiology, as well as to update and clarify the changes that take place in ghrelin concentrations following bariatric/metabolic surgery together with their potential consolidation to outcomes.
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Affiliation(s)
- Carlota Tuero
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
- Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain.
| | - Victor Valenti
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain
- Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain
- CIBEROBN, Instituto de Salud Carlos III, Pamplona, Navarra, Spain
- Obesity and Adipobiology Group, IdiSNA, Pamplona, Spain
| | - Fernando Rotellar
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain
- Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain
- CIBEROBN, Instituto de Salud Carlos III, Pamplona, Navarra, Spain
- Obesity and Adipobiology Group, IdiSNA, Pamplona, Spain
| | - Manuel F Landecho
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain
- Department of Internal Medicine, General Health Check-up unit, Clínica Universidad de Navarra, Pamplona, Spain
| | - Javier A Cienfuegos
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain
- Department of Surgery, Clínica Universidad de Navarra, Pamplona, Spain
- CIBEROBN, Instituto de Salud Carlos III, Pamplona, Navarra, Spain
- Obesity and Adipobiology Group, IdiSNA, Pamplona, Spain
| | - Gema Frühbeck
- Obesity Area, Clínica Universidad de Navarra, Avenida Pio XII 36, 31008, Pamplona, Navarra, Spain.
- CIBEROBN, Instituto de Salud Carlos III, Pamplona, Navarra, Spain.
- Obesity and Adipobiology Group, IdiSNA, Pamplona, Spain.
- Department of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, Spain.
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Borgeraas H, Hofsø D, Hertel JK, Hjelmesaeth J. Comparison of the effect of Roux-en-Y gastric bypass and sleeve gastrectomy on remission of type 2 diabetes: A systematic review and meta-analysis of randomized controlled trials. Obes Rev 2020; 21:e13011. [PMID: 32162437 PMCID: PMC7317556 DOI: 10.1111/obr.13011] [Citation(s) in RCA: 73] [Impact Index Per Article: 14.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2019] [Revised: 01/22/2020] [Accepted: 01/28/2020] [Indexed: 12/18/2022]
Abstract
Bariatric surgery is an effective treatment option for patients with type 2 diabetes mellitus (T2DM) and obesity. This study aims to compare the effects of Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) on remission of T2DM. MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies published between database inception and 21 November 2019. A meta-analysis, using a random effects model, was performed to calculate relative risk (RR) of T2DM remission between the groups in randomized controlled trials (RCTs). Of 2650 records identified, 12 records from 10 different RCTs were finally included. The studies comprised 705 patients with follow-up from 1 to 5 years. The remission rate of T2DM at 1 year was higher among those undergoing RYGB (156/276, 57%) compared with those undergoing SG (128/275, 47%), RR (95% CI) 1.20 (1.00-1.45), P = .047, I2 = 24.9%, moderate-quality evidence. Among studies with 2- to 5-year follow-up, there was no difference in remission rates between the RYGB (132/263, 50%) and SG (121/266, 46%) groups, RR 1.06 (0.94-1.20), P = .34, I2 = 0.0%, low-quality evidence. RYGB resulted in a higher rate of T2DM remission compared with SG after 1 year. The T2DM remission rates did not differ in studies with 2- to 5-year follow-up.
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Affiliation(s)
- Heidi Borgeraas
- Morbid Obesity Centre, Vestfold Hospital Trust, Tønsberg, Norway
| | - Dag Hofsø
- Morbid Obesity Centre, Vestfold Hospital Trust, Tønsberg, Norway
| | | | - Jøran Hjelmesaeth
- Morbid Obesity Centre, Vestfold Hospital Trust, Tønsberg, Norway.,Department of Endocrinology, Morbid Obesity and Preventive Medicine, Institute of Clinical Medicine,, University of Oslo, Oslo, Norway
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Tsouristakis AI, Febres G, McMahon DJ, Tchang B, Conwell IM, Tsang AJ, Ahmed L, Bessler M, Korner J. Long-Term Modulation of Appetitive Hormones and Sweet Cravings After Adjustable Gastric Banding and Roux-en-Y Gastric Bypass. Obes Surg 2020; 29:3698-3705. [PMID: 31376135 DOI: 10.1007/s11695-019-04111-z] [Citation(s) in RCA: 23] [Impact Index Per Article: 4.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) produces greater weight loss compared with a purely restrictive procedure such as laparoscopic adjustable gastric banding (LAGB). OBJECTIVE The objective of this study was to quantify changes in hormones that regulate energy homeostasis and appetitive sensations before and after LAGB (n = 18) and RYGB (n = 38) in order to better understand the mechanisms underlying the greater weight loss after RYGB. METHODS A standardized test meal was administered prior to surgery, at 6 months, and annually thereafter to year 2 after LAGB and year 4 after RYGB. Blood samples were obtained in the fasted state and 30, 60, 90, and 120 min post-meal. RESULTS Progressive increases in fasting PYY were observed after RYGB together with increases in postprandial area under the curve (AUC) levels that were unchanged after LAGB. GLP-1 AUC increased only after RYGB. There was a weight loss-related increase in fasting ghrelin levels after LAGB that was unchanged 1 year after RYGB despite greater percentage weight loss; ghrelin subsequently increased at years 2-4 post-RYGB. HOMA-IR decreased after both procedures but correlated with weight loss only after LAGB, whereas leptin correlated with weight loss in both groups. Sweet cravings decreased after RYGB. CONCLUSION A number of weight loss-independent changes in the gut hormonal milieu likely act in concert to promote a decrease in insulin resistance and greater weight loss efficacy after RYGB. A progressive change in hormone levels over time may reflect gut enteroplasticity after RYGB. A decrease in sweet cravings specific to RYGB may further promote superior weight loss outcomes.
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Affiliation(s)
- Alina I Tsouristakis
- Department of Medicine, Columbia University College of Physicians & Surgeons, 650 West 168th St., BB 20-08, New York, NY, 10032, USA
| | - Gerardo Febres
- Department of Medicine, Columbia University College of Physicians & Surgeons, 650 West 168th St., BB 20-08, New York, NY, 10032, USA
| | - Donald J McMahon
- Department of Medicine, Columbia University College of Physicians & Surgeons, 650 West 168th St., BB 20-08, New York, NY, 10032, USA
| | - Beverly Tchang
- Department of Medicine, Columbia University College of Physicians & Surgeons, 650 West 168th St., BB 20-08, New York, NY, 10032, USA
| | - Irene M Conwell
- Department of Medicine, Columbia University College of Physicians & Surgeons, 650 West 168th St., BB 20-08, New York, NY, 10032, USA
| | - Amanda J Tsang
- Department of Medicine, Columbia University College of Physicians & Surgeons, 650 West 168th St., BB 20-08, New York, NY, 10032, USA
| | - Leaque Ahmed
- Department of Surgery, Wyckoff Heights Hospital, Brooklyn, NY, USA
| | - Marc Bessler
- Department of Surgery, Columbia University College of Physicians & Surgeons, New York, NY, USA
| | - Judith Korner
- Department of Medicine, Columbia University College of Physicians & Surgeons, 650 West 168th St., BB 20-08, New York, NY, 10032, USA.
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Hyde KM, Blonde GD, Bueter M, le Roux CW, Spector AC. Gastric bypass in female rats lowers concentrated sugar solution intake and preference without affecting brief-access licking after long-term sugar exposure. Am J Physiol Regul Integr Comp Physiol 2020; 318:R870-R885. [PMID: 32083966 DOI: 10.1152/ajpregu.00240.2019] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Abstract
In rodents, Roux-en-Y gastric bypass (RYGB) decreases intake of, and preference for, foods or fluids that are high in sugar. Whether these surgically induced changes are due to decreases in the palatability of sugar stimuli is controversial. We used RYGB and sham-operated (SHAM) female rats to test the influence of prolonged ingestive experience with sugar solutions on the motivational potency of these stimuli to drive licking in brief-access (BA) tests. In experiment 1, RYGB attenuated intake of, and caloric preference for, 0.3 M sucrose during five consecutive, 46-h two-bottle tests (TBTs; sucrose). A second series of TBTs (5 consecutive, 46-h tests) with 1.0 M sucrose revealed similar results, except fluid preference for 1.0 M sucrose also significantly decreased. Before, between, and after the two series of TBTs, two sessions of BA tests (30 min; 10-s trials) with an array of sucrose concentrations (0 and 0.01-1.0 M) were conducted. Concentration-dependent licking and overall trial initiation did not differ between surgical groups in any test. In a similar experimental design in a second cohort of female rats, 0.6 and 2.0 M glucose (isocaloric with sucrose concentrations in experiment 1) were used in the TBTs; 0 and 0.06-2.0 M glucose were used in the BA tests. Outcomes were similar to those for experiment 1, except RYGB rats initiated fewer trials during the BA tests. Although RYGB profoundly affected intake of, and caloric preference for, sugar solutions and, with high concentrations, fluid preference, RYGB never influenced the motivational potency of sucrose or glucose to drive concentration-dependent licking in BA tests.
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Affiliation(s)
- Kellie M Hyde
- Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida
| | - Ginger D Blonde
- Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida
| | - Marco Bueter
- Division of Visceral and Transplantation Surgery, Department of Surgery, University of Zürich, Zürich, Switzerland
| | - Carel W le Roux
- Diabetes Complications Research Centre, Conway Institute, School of Medicine, University College Dublin, Dublin, Ireland
| | - Alan C Spector
- Department of Psychology and Program in Neuroscience, Florida State University, Tallahassee, Florida
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Salman MA, El-Ghobary M, Soliman A, El Sherbiny M, Abouelregal TE, Albitar A, Abdallah A, Mikhail HMS, Nafea MA, Sultan AAEA, Elshafey HE, Shaaban HED, Azzam A, GabAllah GMK, Salman AA. Long-Term Changes in Leptin, Chemerin, and Ghrelin Levels Following Roux-en-Y Gastric Bypass and Laparoscopic Sleeve Gastrectomy. Obes Surg 2020; 30:1052-1060. [PMID: 31713147 DOI: 10.1007/s11695-019-04254-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
AIM Published reports showed conflicting results regarding the sustained alterations in leptin, chemerin, and ghrelin concenratios after metabolic surgery. Therefore, we performed the present work to contrast the alterations in leptin, chemerin, and ghrelin levels one year after Roux-en-Y gastric bypass (RYGB) versus laparoscopic sleeve gastrectomy (LSG). METHODS The present research is a prospective, comparative one that followed 100 cases for whom RYGB or LSG was done. We assessed the serum values of adiposity-associated mediators, including adipokcytokines (leptin and active chemerin) and gastrointestinal hormones (total ghrelin). The primary outcome in the present study was the alterations in leptin, chemerin, and ghrelin values at 12 months after RYGB and LSG. RESULTS The serum leptin level decreased significantly in the LSG group with a mean change of - 170.8 ± 29.4 ng/mL (p < 0.001). Similarly, the serum leptin concentration decreased significantly in the RYGB group, with a mean change of - 165.42 ± 53.4 (p < 0.001). In addition, the mean reduction in baseline chemerin levels 12 months after the operation was considerable in the LSG cohort (- 23.24 ± 9.5 ng/mL) and RYGB group (- 22.12 ± 15.9 ng/mL). The ghrelin values demonstrated a notable reduction in the LSG cohort (- 0.083 ± 0.11 pg/mL) and RYGB group (- 0.068 ± 0.097 pg/mL). However, the changes in the three hormones were not substantially different between both groups (p > 0.05). CONCLUSION Both RYGB and LSG result in a considerable, comparable decrease in the postoperative serum concentrations of leptin, chemerin, and ghrelin.
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Affiliation(s)
| | - Mohamed El-Ghobary
- Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Ahmed Soliman
- Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Mohammad El Sherbiny
- Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | | | - Amr Albitar
- Internal Medicine Department, Faculty of Medicine, Cairo University, Giza, Egypt
| | - Ahmed Abdallah
- General Surgery Department, Faculty of Medicine, Cairo University, Giza, 11311, Egypt
| | | | - Mohammed A Nafea
- General Surgery Department, Faculty of Medicine, Al Azhar University, Cairo, Egypt
| | | | - Hossam E Elshafey
- General Surgery Department, Faculty of Medicine, Helwan University, Helwan, Egypt
| | | | - Ayman Azzam
- Clinical Biochemistry Department, National Liver Institute, Menoufia University, Shibin el Kom, Egypt
| | - Ghada M K GabAllah
- Medical Biochemistry Department, Faculty of Medicine, Menoufia University, Shibin el Kom, Egypt
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Navarro García MI, González-Costea Martínez R, Torregrosa Pérez N, Romera Barba E, Periago MJ, Vázquez Rojas JL. Fasting ghrelin levels after gastric bypass and vertical sleeve gastrectomy: An analytical cohort study. ENDOCRINOLOGÍA, DIABETES Y NUTRICIÓN (ENGLISH ED.) 2020. [DOI: 10.1016/j.endien.2019.07.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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Dischinger U, Hasinger J, Königsrainer M, Corteville C, Otto C, Fassnacht M, Hankir M, Seyfried FJD. Toward a Medical Gastric Bypass: Chronic Feeding Studies With Liraglutide + PYY 3-36 Combination Therapy in Diet-Induced Obese Rats. Front Endocrinol (Lausanne) 2020; 11:598843. [PMID: 33551994 PMCID: PMC7862770 DOI: 10.3389/fendo.2020.598843] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 12/07/2020] [Indexed: 12/31/2022] Open
Abstract
BACKGROUND Combination therapies of anorectic gut hormones partially mimic the beneficial effects of bariatric surgery. Thus far, the effects of a combined chronic systemic administration of Glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine 3-36 (PYY3-36) have not been directly compared to Roux-en-Y gastric bypass (RYGB) in a standardized experimental setting. METHODS High-fat diet (HFD)-induced obese male Wistar rats were randomized into six treatment groups: (1) RYGB, (2) sham-operation (shams), (3) liraglutide, (4) PYY3-36, (5) PYY3-36+liraglutide (6), saline. Animals were kept on a free choice high- and low-fat diet. Food intake, preference, and body weight were measured daily for 4 weeks. Open field (OP) and elevated plus maze (EPM) tests were performed. RESULTS RYGB reduced food intake and achieved sustained weight loss. Combined PYY3-36+liraglutide treatment led to similar and plateaued weight loss compared to RYGB. Combined PYY3-36+liraglutide treatment was superior to PYY3-36 (p ≤ 0.0001) and liraglutide (p ≤ 0.05 or p ≤ 0.01) mono-therapy. PYY3-36+liraglutide treatment and RYGB also reduced overall food intake and (less pronounced) high-fat preference compared to controls. The animals showed no signs of abnormal behavior in OF or EPM. CONCLUSIONS Liraglutide and PYY3-36 combination therapy vastly mimics reduced food intake, food choice and weight reducing benefits of RYGB.
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Affiliation(s)
- Ulrich Dischinger
- Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany
- *Correspondence: Ulrich Dischinger,
| | - Julia Hasinger
- Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany
| | - Malina Königsrainer
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany
| | - Carolin Corteville
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany
| | - Christoph Otto
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany
| | - Martin Fassnacht
- Department of Internal Medicine, Division of Endocrinology and Diabetes, University Hospital, University of Würzburg, Würzburg, Germany
| | - Mohamed Hankir
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany
| | - Florian Johannes David Seyfried
- Department of General, Visceral, Transplant, Vascular and Pediatric Surgery, University Hospital, University of Würzburg, Würzburg, Germany
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Korakas E, Kountouri A, Raptis A, Kokkinos A, Lambadiari V. Bariatric Surgery and Type 1 Diabetes: Unanswered Questions. Front Endocrinol (Lausanne) 2020; 11:525909. [PMID: 33071965 PMCID: PMC7531037 DOI: 10.3389/fendo.2020.525909] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2020] [Accepted: 08/20/2020] [Indexed: 01/19/2023] Open
Abstract
In recent decades there has been an alarming increase in the prevalence of obesity in patients with type 1 diabetes leading to the development of insulin resistance and cardiometabolic complications, with mechanisms poorly clarified. While bariatric surgery has long been considered an effective treatment option for patients with type 2 diabetes, the evidence regarding its benefits on weight loss and the prevention of complications in T1DM patients is scarce, with controversial outcomes. Bariatric surgery has been associated with a significant reduction in daily insulin requirement, along with a considerable reduction in body mass index, results which were sustained in the long term. Furthermore, studies suggest that bariatric surgery in type 1 diabetes results in the improvement of comorbidities related to obesity including hypertension and dyslipidemia. However, regarding glycemic control, the reduction of mean glycosylated hemoglobin was modest or statistically insignificant in most studies. The reasons for these results are yet to be elucidated; possible explanations include preservation of beta cell mass and increased residual function post-surgery, improvement in insulin action, altered GLP-1 function, timing of surgery, and association with residual islet cell mass. A number of concerns regarding safety issues have arisen due to the reporting of peri-operative and post-operative adverse events. The most significant complications are metabolic and include diabetic ketoacidosis, severe hypoglycemia and glucose fluctuations. Further prospective clinical studies are required to provide evidence for the effect of bariatric surgery on T1DM patients. The results may offer a better knowledge for the selection of people living with diabetes who will benefit more from a metabolic surgery.
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Affiliation(s)
- Emmanouil Korakas
- Second Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Aikaterini Kountouri
- Second Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Athanasios Raptis
- Second Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Alexander Kokkinos
- First Department of Propaedeutic Medicine, Medical School, Laiko General Hospital, National and Kapodistrian University of Athens, Athens, Greece
| | - Vaia Lambadiari
- Second Department of Internal Medicine, Medical School, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
- *Correspondence: Vaia Lambadiari
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Sanches E, Timmermans M, Topal B, Celik A, Sundbom M, Ribeiro R, Parmar C, Ugale S, Proczko M, Stepaniak PS, Pujol Rafols J, Mahawar K, Buise MP, Neimark A, Severin R, Pouwels S. Cardiac remodeling in obesity and after bariatric and metabolic surgery; is there a role for gastro-intestinal hormones? Expert Rev Cardiovasc Ther 2019; 17:771-790. [PMID: 31746657 DOI: 10.1080/14779072.2019.1690991] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Introduction: Obesity is associated with various diseases such as type 2 diabetes, hypertension, obstructive sleep apnea syndrome (OSAS), metabolic syndrome, and cardiovascular diseases. It affects several organ systems, including the pulmonary and cardiac systems. Furthermore, it induces pulmonary and cardiac changes that can result in right and/or left heart failure.Areas covered: In this review, authors provide an overview of obesity and cardiovascular remodeling, the individual actions of the gut hormones (like GLP-1 and PYY), the effects after bariatric/metabolic surgery and its influence on cardiac remodeling. In this review, we focussed and searched for literature in Pubmed and The Cochrane library (from the earliest date until April 2019), regarding cardiac function changes before and after bariatric surgery and literature regarding changes in gastrointestinal hormones.Expert opinion: Regarding the surgical treatment of obesity and metabolic diseases there is recognition of the importance of both weight loss (bariatric surgery) and improvement in metabolic milieu (metabolic surgery). A growing body of evidence further suggests that bariatric surgical procedures [like the Sleeve Gastrectomy (SG), Roux-en Y Gastric Bypass (RYGB), or One Anastomosis Gastric Bypass (OAGB)] have can improve outcomes of patients suffering from a number of cardiovascular diseases, including heart failure.
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Affiliation(s)
- Elijah Sanches
- Department of Surgery, Haaglanden Medical Center, The Hague, The Netherlands
| | - Marieke Timmermans
- Department of Surgery, Haaglanden Medical Center, The Hague, The Netherlands
| | - Besir Topal
- Department of Cardiothoracic Surgery, Onze Lieve Vrouwe Gasthuis, Amsterdam, The Netherlands
| | - Alper Celik
- Department of Bariatric and Metabolic Surgery, Metabolic Surgery Clinic, Sisli, Turkey
| | - Magnus Sundbom
- Department of Surgical Sciences, Uppsala University, Uppsala, Sweden
| | - Rui Ribeiro
- Centro Multidisciplinar da Doença Metabólica, Clínica de Santo António, Lisbon, Portugal
| | - Chetan Parmar
- Department of Surgery, Whittington Hospital, London, UK
| | - Surendra Ugale
- Bariatric & Metabolic Surgery Clinic, Kirloskar Hospital, Hyderabad, India
| | - Monika Proczko
- Department of General, Endocrine and Transplant Surgery, University Medical Center, Gdansk University, Gdansk, Poland
| | - Pieter S Stepaniak
- Department of Operating Rooms, Catharina Hospital, Eindhoven, The Netherlands
| | | | - Kamal Mahawar
- Bariatric Unit, Sunderland Royal Hospital, Sunderland, UK
| | - Marc P Buise
- Department of Anesthesiology, Intensive Care and Pain Medicine, Catharina Hospital, Eindhoven, The Netherlands
| | - Aleksandr Neimark
- Department of Surgery, Almazov National Medical Research Centre, Saint Petersburg, Russia
| | - Rich Severin
- Department of Physical Therapy, College of Applied Health Sciences, University of Illinois at Chicago, Chicago, IL, USA.,Doctor of Physical Therapy Program, Robbins College of Health and Human Sciences, Baylor University, Waco, TX, USA
| | - Sjaak Pouwels
- Department of Surgery, Haaglanden Medical Center, The Hague, The Netherlands
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Navarro García MI, González-Costea Martínez R, Torregrosa Pérez N, Romera Barba E, Periago MJ, Vázquez Rojas JL. Fasting ghrelin levels after gastric bypass and vertical sleeve gastrectomy: An analytic cohort study. ACTA ACUST UNITED AC 2019; 67:89-101. [PMID: 31680051 DOI: 10.1016/j.endinu.2019.07.004] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2018] [Revised: 06/02/2019] [Accepted: 07/01/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVE Neuronal populations involved in the regulation of food intake, particularly the orexigenic (appetite-stimulating) hormone ghrelin, are found in the hypothalamus. Changes in plasma ghrelin levels have been observed following different bariatric surgery procedures, but the results from different studies are contradictory. Much remains unknown regarding the role of ghrelin in the weight loss process following bariatric surgery. Our objective was to describe the behaviour of fasting ghrelin levels, comparing the changes occurring between 2 different surgical techniques (gastric bypass versus vertical sleeve gastrectomy) and their correlation with weight loss. PATIENTS AND METHOD A prospective, observational, analytic cohort study of 54 patients (27 for each surgical technique) with a 12-month follow-up period. We analysed demographic data, anthropometric data, comorbidities, weight loss and evolution of fasting ghrelin. RESULTS The behaviour of acylated ghrelin was similar with the 2 surgical techniques, with no significant differences between gastric bypass and vertical sleeve gastrectomy. With both procedures, there was an increase in acylated ghrelin on day 5 and a subsequent decrease, and levels then gradually increased to reach values at 12 months that were higher than those reported preoperatively. This increase in ghrelin levels did not affect weight loss, since one year post-surgery, 30% weight loss was achieved with both types of surgery. CONCLUSIONS We observed an increase in fasting acylated ghrelin levels at one year of follow-up with both surgical techniques, with 30% weight loss.
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Affiliation(s)
| | | | - Nuría Torregrosa Pérez
- Unidad de Obesidad Mórbida, Servicio de Cirugía General, Hospital Santa Lucía de Cartagena, Murcia, España
| | - Elena Romera Barba
- Unidad de Obesidad Mórbida, Servicio de Cirugía General, Hospital Santa Lucía de Cartagena, Murcia, España
| | - María Jesús Periago
- Grupo de Investigación de Nutrición y Bromatología de la Universidad de Murcia, Murcia, España
| | - José Luis Vázquez Rojas
- Unidad de Obesidad Mórbida, Servicio de Cirugía General, Hospital Santa Lucía de Cartagena, Murcia, España
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Shan CX, Qiu NC, Liu ME, Zha SL, Song X, Du ZP, Rao WS, Jiang DZ, Zhang W, Qiu M. Effects of Diet on Bile Acid Metabolism and Insulin Resistance in Type 2 Diabetic Rats after Roux-en-Y Gastric Bypass. Obes Surg 2019; 28:3044-3053. [PMID: 29721762 DOI: 10.1007/s11695-018-3264-2] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) is effective for the treatment of type 2 diabetes mellitus; however, the mechanism remains unclear. METHODS The effects of RYGB on postprandial responses to three different diets (low carbohydrate (CH)-rich diet, high CH-rich diet, and fat-rich diet) of different nutritional composition in a Goto-Kakizaki (GK) diabetic rat model were assessed by measuring glucose tolerance, insulin resistance, incretin responses, and bile acid (BA) metabolism. RESULTS GK-RYGB group rats lost weight and preferred low CH-rich diet, but there were no significant differences in BW among the different diets. Glucose tolerance and insulin resistance were improved in rats who underwent RYGB, together with higher levels of circulating BAs, plasma GLP-1, and PYY levels. GK-RYGB rats fed high CH-rich or fat-rich diet showed increased glucose level and insulin resistance, together with high plasma BA, GIP, and PYY levels compared to those fed a low CH-rich diet. CONCLUSION RYGB improves glucose tolerance and insulin resistance which may be related to BA metabolism and hormone levels, and the nutrient composition of the diet affects the treatment effect of RYGB on T2DM.
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Affiliation(s)
- Cheng-Xiang Shan
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Nian-Cun Qiu
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China.,Department of General Surgery, Hainan Branch of Chinese PLA General Hospital, Sanya, 572000, China
| | - Miao-E Liu
- Key Laboratory of Reproductive Genetics, Women's Hospital, Zhejiang University, Zhejiang, 310000, China
| | - Si-Luo Zha
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Xin Song
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Zhi-Peng Du
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Wen-Sheng Rao
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Dao-Zhen Jiang
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Wei Zhang
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China.
| | - Ming Qiu
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China.
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Lesti G, Aiolfi A, Mozzi E, Altorio F, Lattuada E, Lesti F, Bonitta G, Zappa MA. Laparoscopic Gastric Bypass with Fundectomy and Gastric Remnant Exploration (LRYGBfse): Results at 5-Year Follow-up. Obes Surg 2019; 28:2626-2633. [PMID: 29623665 DOI: 10.1007/s11695-018-3220-1] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
BACKGROUND The laparoscopic Roux-en-Y gastric bypass (LRYGB) is the gold standard treatment for morbid obesity. After LRYGB, the endoscopic access to the gastric remnant and pancreaticobiliary system is challenging. The laparoscopic gastric bypass with fundectomy and exploration of the gastric remnant (LRYGBfse) was introduced in an attempt to overcome this limitation. The purpose of this study was to analyze the medium-term outcomes and safety of LRYGBfse. METHODS Observational prospective single-arm multicenter cohort study. Patients with BMI > 35 kg/m2 were included. Previous open abdominal surgery was an exclusion criterion. Postoperative 1, 2, 3, and 5-year weight loss, BMI decrease, and percentage of excess weight loss (%EWL) were recorded. Wilcoxon signed rank sum test was used for paired data. RESULTS Among 653 enrolled patients, 229 completed the 5-year follow-up. Preoperative median body weight (kg) and BMI (kg/m2) were 133.4 kg (interquartile range (IQR) = 12.0) and 48.2 kg/m2 (IQR = 10.1), respectively. Median 5-year body weight, BMI, and %EWL were 83.7 (IQR = 17.3), 31.2 (IQR = 7.7), and 74.8 (IQR = 23.4), respectively, all significantly improved compared to baseline (p = 0.002, p = 0.001, and p = 0.012, respectively). Comorbid improvement or resolution was observed in 88% of the patients. No major intraoperative complications were reported. Postoperative overall morbidity and mortality rates were 1 and 0%, respectively. Banding removal was necessary in one patient 62 months after the index operation. CONCLUSIONS The LRYGBfse seems safe and effective with durable results at 5-year follow-up. Endoscopic exploration of the gastric remnant is an additional valuable tool.
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Affiliation(s)
- Giovanni Lesti
- Department of General Surgery, Fondazione Salus Clinica Di Lorenzo, Via Vittorio Veneto n 37, Avezzano, L'Aquila, Italy
| | - Alberto Aiolfi
- Department of Biomedical Science for Health, Division of General and Emergency Surgery, University of Milan, Milan, Milan, Italy.
| | - Enrico Mozzi
- Division of General Surgery, Istituto Auxologico Italiano - IRCCS, Milan, Milan, Italy
| | - Fabrizio Altorio
- Department of General Surgery, Fondazione Salus Clinica Di Lorenzo, Via Vittorio Veneto n 37, Avezzano, L'Aquila, Italy
| | - Ezio Lattuada
- Department of General Surgery, Istituto Clinico Humanitas San Pio X, Humanitas University, Milan, Milan, Italy
| | - Francesco Lesti
- Department of General Surgery, Fondazione Salus Clinica Di Lorenzo, Via Vittorio Veneto n 37, Avezzano, L'Aquila, Italy
| | - Gianluca Bonitta
- Department of Biomedical Science for Health, Division of General and Emergency Surgery, University of Milan, Milan, Milan, Italy
| | - Marco Antonio Zappa
- Department of General and Emergency Surgery, Ospedale Fatebenefratelli Sacra Famiglia, University of Milan, Erba, Como, Italy
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Boland B, Mumphrey MB, Hao Z, Gill B, Townsend RL, Yu S, Münzberg H, Morrison CD, Trevaskis JL, Berthoud HR. The PYY/Y2R-Deficient Mouse Responds Normally to High-Fat Diet and Gastric Bypass Surgery. Nutrients 2019; 11:E585. [PMID: 30857366 PMCID: PMC6471341 DOI: 10.3390/nu11030585] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2019] [Revised: 03/04/2019] [Accepted: 03/05/2019] [Indexed: 12/18/2022] Open
Abstract
BACKGROUND/GOALS The gut hormone peptide YY (PYY) secreted from intestinal L-cells has been implicated in the mechanisms of satiation via Y2-receptor (Y2R) signaling in the brain and periphery and is a major candidate for mediating the beneficial effects of bariatric surgery on appetite and body weight. METHODS Here we assessed the role of Y2R signaling in the response to low- and high-fat diets and its role in the effects of Roux-en-Y gastric bypass (RYGB) surgery on body weight, body composition, food intake, energy expenditure and glucose handling, in global Y2R-deficient (Y2RKO) and wildtype (WT) mice made obese on high-fat diet. RESULTS Both male and female Y2RKO mice responded normally to low- and high-fat diet in terms of body weight, body composition, fasting levels of glucose and insulin, as well as glucose and insulin tolerance for up to 30 weeks of age. Contrary to expectations, obese Y2RKO mice also responded similarly to RYGB compared to WT mice for up to 20 weeks after surgery, with initial hypophagia, sustained body weight loss, and significant improvements in fasting insulin, glucose tolerance, insulin resistance (HOMA-IR), and liver weight compared to sham-operated mice. Furthermore, non-surgical Y2RKO mice weight-matched to RYGB showed the same improvements in glycemic control as Y2RKO mice with RYGB that were similar to WT mice. CONCLUSIONS PYY signaling through Y2R is not required for the normal appetite-suppressing and body weight-lowering effects of RYGB in this global knockout mouse model. Potential compensatory adaptations of PYY signaling through other receptor subtypes or other gut satiety hormones such as glucagon-like peptide-1 (GLP-1) remain to be investigated.
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Affiliation(s)
- Brandon Boland
- Cardiovascular, Renal & Metabolic Diseases, MedImmune, Gaithersburg, MD 20878, USA.
| | - Michael B Mumphrey
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
| | - Zheng Hao
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
| | - Benji Gill
- Cardiovascular, Renal & Metabolic Diseases, MedImmune, Gaithersburg, MD 20878, USA.
| | - R Leigh Townsend
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
| | - Sangho Yu
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
| | - Heike Münzberg
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
| | - Christopher D Morrison
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
| | - James L Trevaskis
- Cardiovascular, Renal & Metabolic Diseases, MedImmune, Gaithersburg, MD 20878, USA.
| | - Hans-Rudolf Berthoud
- Neurobiology of Nutrition & Metabolism Department, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA.
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Mullally JA, Febres GJ, Bessler M, Korner J. Sleeve Gastrectomy and Roux-en-Y Gastric Bypass Achieve Similar Early Improvements in Beta-cell Function in Obese Patients with Type 2 Diabetes. Sci Rep 2019; 9:1880. [PMID: 30755673 PMCID: PMC6372630 DOI: 10.1038/s41598-018-38283-y] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2018] [Accepted: 12/18/2018] [Indexed: 01/08/2023] Open
Abstract
Bariatric surgery is a treatment option for obese patients with type 2 diabetes mellitus (T2DM). Although sleeve gastrectomy (SG) is growing in favor, some randomized trials show less weight loss and HbA1c improvement compared with Roux-en-Y gastric bypass (RYGB). The study objective was to compare changes in beta-cell function with similar weight loss after SG and RYGB in obese patients with T2DM. Subjects undergoing SG or RYGB were studied with an intravenous glucose tolerance test before surgery and at 5–12% weight loss post-surgery. The primary endpoint was change in the disposition index (DI). Baseline BMI, HbA1c, and diabetes-duration were similar between groups. Mean total weight loss percent was similar (8.4% ± 0.4, p = 0.22) after a period of 21.0 ± 1.7 days. Changes in fasting glucose, acute insulin secretion (AIR), and insulin sensitivity (Si) were similar between groups. Both groups showed increases from baseline to post-surgery in DI (20.2 to 163.3, p = 0.03 for SG; 31.2 to 232.9, p = 0.02 for RYGB) with no significant difference in the change in DI between groups (p = 0.53). Short-term improvements in beta-cell function using an IVGTT were similar between SG and RYGB. It remains unclear if longer-term outcomes are better after RYGB due to greater weight loss and/or other factors.
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Affiliation(s)
- Jamie A Mullally
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA
| | - Gerardo J Febres
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA
| | - Marc Bessler
- Department of Surgery, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA
| | - Judith Korner
- Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, 10032, USA.
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42
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Ouyang X, Li S, Tan Y, Lin L, Yin J, Chen JDZ. Intestinal electrical stimulation attenuates hyperglycemia and prevents loss of pancreatic β cells in type 2 diabetic Goto-Kakizaki rats. Nutr Diabetes 2019; 9:4. [PMID: 30728346 PMCID: PMC6365494 DOI: 10.1038/s41387-019-0072-2] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/15/2018] [Revised: 11/01/2018] [Accepted: 11/28/2018] [Indexed: 01/30/2023] Open
Abstract
BACKGROUND/OBJECTIVE Recently, intestinal electrical stimulation (IES) has been reported to result in weight loss; however, it is unclear whether it has a therapeutic potential for diabetes. The aim of the present study was to explore the potential hypoglycemic effects of IES and its possible mechanisms involving β cells in diabetic rats. SUBJECTS/METHODS Diabetic Goto-Kakizaki (GK) rats were chronically implanted with one pair of electrodes in the duodenum. The oral glucose tolerance test (OGTT) and insulin tolerance test (ITT) were performed with or without IES, and plasma glucagon-like peptide-1 (GLP-1) and insulin level were measured. In the other two OGTT sessions, rats were treated with either Exendin (9-39) (GLP-1 antagonist) or Exendin (9-39) plus IES to investigate the underlying mechanism involving GLP-1. Gastric emptying and small intestinal transit were also measured with or without IES. In a chronic study, GK rats were treated with IES or Sham-IES for 8 weeks. Blood glucose, plasma GLP-1 and insulin level, body weight, and food intake were measured. Pancreas weight, islet β-cell apoptosis, and proliferation were also analyzed. RESULTS Acute IES reduced blood glucose level from 60 to 120 min during OGTT by 16-20% (all p < 0.05, vs. Sham-IES). GLP-1 antagonist significantly blocked the inhibitory effect of IES on hyperglycemia from 15 to 120 min (all p < 0.05). IES accelerated the small intestinal transit by 15% (p = 0.004). After 8 weeks of chronic stimulation, IES significantly reduced blood glucose (p < 0.05) and body weight (p = 0.02) and increased the plasma GLP-1 concentration (p < 0.05). Furthermore, we observed that chronic IES reduced pancreatic β-cell apoptosis (p = 0.045), but showed no effects on β-cell proliferation. CONCLUSIONS Our study firstly proved the hypoglycemic effect of IES in a rodent model of type 2 diabetes, possibly attributed to the increasing GLP-1 secretion and improvement in β-cell functions.
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Affiliation(s)
- Xiaojun Ouyang
- Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA.,Division of Geriatrics and Gerontology, Geriatric Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Shiying Li
- Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA.,Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Yan Tan
- Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA.,Division of Gastroenterology, The First Affiliated Hospital of Hainan Medical University, Haikou, Hainan, China
| | - Lin Lin
- Division of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, China
| | - Jieyun Yin
- Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA.,Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Jiande D Z Chen
- Veterans Research and Education Foundation, VA Medical Center, Oklahoma City, OK, USA. .,Division of Gastroenterology and Hepatology, Johns Hopkins University, Baltimore, MD, USA.
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Al-Najim W, Docherty NG, le Roux CW. Food Intake and Eating Behavior After Bariatric Surgery. Physiol Rev 2018; 98:1113-1141. [PMID: 29717927 DOI: 10.1152/physrev.00021.2017] [Citation(s) in RCA: 108] [Impact Index Per Article: 15.4] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Obesity is an escalating global chronic disease. Bariatric surgery is a very efficacious treatment for obesity and its comorbidities. Alterations to gastrointestinal anatomy during bariatric surgery result in neurological and physiological changes affecting hypothalamic signaling, gut hormones, bile acids, and gut microbiota, which coalesce to exert a profound influence on eating behavior. A thorough understanding of the mechanisms underlying eating behavior is essential in the management of patients after bariatric surgery. Studies investigating candidate mechanisms have expanded dramatically in the last decade. Herein we review the proposed mechanisms governing changes in eating behavior, food intake, and body weight after bariatric surgery. Additive or synergistic effects of both conditioned and unconditioned factors likely account for the complete picture of changes in eating behavior. Considered application of strategies designed to support the underlying principles governing changes in eating behavior holds promise as a means of optimizing responses to surgery and long-term outcomes.
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Affiliation(s)
- Werd Al-Najim
- Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland ; Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden ; and Investigative Science, Imperial College London , London , United Kingdom
| | - Neil G Docherty
- Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland ; Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden ; and Investigative Science, Imperial College London , London , United Kingdom
| | - Carel W le Roux
- Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College Dublin , Dublin , Ireland ; Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg , Gothenburg , Sweden ; and Investigative Science, Imperial College London , London , United Kingdom
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Adaptation of Intestinal and Bile Acid Physiology Accompany the Metabolic Benefits Following Ileal Interposition in the Rat. Obes Surg 2018; 28:725-734. [PMID: 28861731 DOI: 10.1007/s11695-017-2886-0] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
PURPOSE Ileal interposition recapitulates many of the metabolic improvements similar to Roux-en-Y gastric bypass. We aimed to determine whether the metabolic improvements seen following ileal interposition were conferred solely by the interposed segment by examining changes in neighboring intestinal segments as well as the composition of the bile acid pool. MATERIALS AND METHODS Adult male rats were treated with either sham or ileal interposition surgeries. Glucose tolerance tests, body composition analysis, polymer chain reaction, enzyme-linked immunosorbent assay, and mass spectrometry were done after the surgeries. RESULTS This study showed that ileal interposition improved glucose tolerance and enhanced both fasting and glucose-stimulated GLP-1 secretion in diabetic rats. Total bile acid pool was similar between groups but the composition favored glycine-conjugation in rats with ileal interposition. Insulin secretion was highly correlated with the 12-alpha-hydroxylase index of activity. The interposed ileum exhibited an increase in mRNA for preproglucagon and peptide YY; however, the bile acid transporter, apical sodium bile acid transporter, was dramatically reduced compared to sham rats. The interposed segment becomes jejunized in its new location as indicated by an increase in Glut2 and Pepck mRNA, genes predominantly synthesized within the jejunum. CONCLUSION Ileal relocation alone can significantly alter the bile acid pool to favor a more insulin-sensitive metabolism in association with intestinal wide alterations in mRNA for a variety of genes. Ileal interposition may confer metabolic improvement via both the interposed segment and the associated intestinal changes in all segments of the intestine, including the colon.
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45
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Fealy CE, Mulya A, Axelrod CL, Kirwan JP. Mitochondrial dynamics in skeletal muscle insulin resistance and type 2 diabetes. Transl Res 2018; 202:69-82. [PMID: 30153426 DOI: 10.1016/j.trsl.2018.07.011] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/12/2018] [Revised: 07/08/2018] [Accepted: 07/23/2018] [Indexed: 01/09/2023]
Abstract
The traditional view of mitochondria as isolated, spherical, energy producing organelles, is undergoing a revolutionary change. Emerging data show that mitochondria form a dynamic reticulum that is regulated by cycles of fission and fusion. The discovery of proteins that modulate these activities has led to important advances in understanding human disease. Here, we review the latest evidence that connects the emerging field of mitochondrial dynamics to skeletal muscle insulin resistance and propose some potential mechanisms that may explain the long debated link between mitochondria and the development of type 2 diabetes.
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Affiliation(s)
- CiarÁn E Fealy
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Anny Mulya
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio
| | - Christopher L Axelrod
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana
| | - John P Kirwan
- Department of Pathobiology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio; Integrated Physiology and Molecular Metabolism Laboratory, Pennington Biomedical Research Center, Baton Rouge, Louisiana.
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Abstract
Pregnancy in women with obesity is an important public health problem with short- and long-term implications for maternal and child health. Obesity complicates almost all aspects of pregnancy. Given the growing prevalence of obesity in women, obstetric providers need to understand the risks associated with obesity in pregnancy and the unique aspects of management for women with obesity. Empathic and patient-centered care, along with knowledge, can optimize outcomes for women and children.
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Affiliation(s)
- Cara D Dolin
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, New York University Langone Health, 550 1st Avenue, New York, NY 10016, USA.
| | - Michelle A Kominiarek
- Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, Northwestern University, 250 East Superior Street Suite 05-2175, Chicago, IL 60611, USA
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Shin DW, Suh B, Park Y, Lim H, Suh YS, Yun JM, Cho B, Yang HK. Risk of Coronary Heart Disease and Ischemic Stroke Incidence in Gastric Cancer Survivors: A Nationwide Study in Korea. Ann Surg Oncol 2018; 25:3248-3256. [PMID: 30043317 DOI: 10.1245/s10434-018-6635-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/19/2018] [Indexed: 12/31/2022]
Abstract
BACKGROUND Small studies suggest improvement of cardiovascular risk profiles and reduced cardiovascular mortality after gastrectomy for gastric cancer. In our study using national health insurance data, we investigated coronary heart disease (CHD) and ischemic stroke incidence among gastric cancer patients who received gastrectomy compared with general population controls. METHODS A total of 98,936 gastric cancer patients were included in the study and matched to non-cancer controls via 1:1 propensity score matching. Competing risk regression analysis was used to determine the relative risk of CHD and ischemic stroke, with cancer mortality as the competing risk. Changes in cardiovascular risk profile before and after gastrectomy were tested, and factors associated with CHD or ischemic stroke incidence among gastric cancer patients were analyzed. RESULTS Compared with the matched controls, gastric cancer patients who received gastrectomy were shown to have a decreased risk for both CHD (subdistribution hazard ratio [SHR] 0.60, 95% confidence interval [CI] 0.57-0.63) and ischemic stroke (SHR 0.72, 95% CI 0.69-0.75). Decreases in body mass index (BMI), blood pressure, blood sugar, and lipid and hemoglobin levels were marked after gastrectomy. Among gastric cancer patients, those who lost > 5% of their body weight were at lower risk of developing CHD (SHR 0.82, 95% CI 0.71-0.96) and ischemic stroke (SHR 0.85, 95% CI 0.75-0.98). CONCLUSIONS CHD and ischemic stroke risk decreased after gastrectomy. The amount of weight loss and accompanying metabolic changes seemed to mediate the reduction of such risk. Reassessment of cardiovascular risk factors after gastrectomy and consideration of cardiovascular risk in the selection of treatment modality are suggested.
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Affiliation(s)
- Dong Wook Shin
- Department of Family Medicine and Supportive Care Center, Samsung Comprehensive Cancer Center, Samsung Medical Center, Seoul, Republic of Korea
| | | | - Youngmin Park
- Department of Family Medicine, National Health Insurance Service Ilsan Hospital, Goyang-si, Gyeonggi-do, Republic of Korea.
| | - Hyunsun Lim
- Department of Policy Research Affairs, National Health Insurance Service Ilsan Hospital, Goyang-si, Gyeonggi-do, Republic of Korea
| | - Yun-Suhk Suh
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
| | - Jae Moon Yun
- Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - BeLong Cho
- Department of Family Medicine, Seoul National University Hospital, Seoul, Republic of Korea
| | - Han-Kwang Yang
- Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea
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Bliss ES, Whiteside E. The Gut-Brain Axis, the Human Gut Microbiota and Their Integration in the Development of Obesity. Front Physiol 2018; 9:900. [PMID: 30050464 PMCID: PMC6052131 DOI: 10.3389/fphys.2018.00900] [Citation(s) in RCA: 121] [Impact Index Per Article: 17.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2018] [Accepted: 06/21/2018] [Indexed: 12/17/2022] Open
Abstract
Obesity is a global epidemic, placing socioeconomic strain on public healthcare systems, especially within the so-called Western countries, such as Australia, United States, United Kingdom, and Canada. Obesity results from an imbalance between energy intake and energy expenditure, where energy intake exceeds expenditure. Current non-invasive treatments lack efficacy in combating obesity, suggesting that obesity is a multi-faceted and more complex disease than previously thought. This has led to an increase in research exploring energy homeostasis and the discovery of a complex bidirectional communication axis referred to as the gut-brain axis. The gut-brain axis is comprised of various neurohumoral components that allow the gut and brain to communicate with each other. Communication occurs within the axis via local, paracrine and/or endocrine mechanisms involving a variety of gut-derived peptides produced from enteroendocrine cells (EECs), including glucagon-like peptide 1 (GLP1), cholecystokinin (CCK), peptide YY3-36 (PYY), pancreatic polypeptide (PP), and oxyntomodulin. Neural networks, such as the enteric nervous system (ENS) and vagus nerve also convey information within the gut-brain axis. Emerging evidence suggests the human gut microbiota, a complex ecosystem residing in the gastrointestinal tract (GIT), may influence weight-gain through several inter-dependent pathways including energy harvesting, short-chain fatty-acids (SCFA) signalling, behaviour modifications, controlling satiety and modulating inflammatory responses within the host. Hence, the gut-brain axis, the microbiota and the link between these elements and the role each plays in either promoting or regulating energy and thereby contributing to obesity will be explored in this review.
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Affiliation(s)
- Edward S. Bliss
- School of Health and Wellbeing, University of Southern Queensland, Toowoomba, QLD, Australia
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Andrew CA, Umashanker D, Aronne LJ, Shukla AP. Intestinal and Gastric Origins for Diabetes Resolution After Bariatric Surgery. Curr Obes Rep 2018; 7:139-146. [PMID: 29637413 DOI: 10.1007/s13679-018-0302-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW This paper will review the intestinal and gastric origins for diabetes resolution after bariatric surgery. RECENT FINDINGS In addition to the known metabolic effects of changes in the gut hormonal milieu, more recent studies investigating the role of the microbiome and bile acids and changes in nutrient sensing mechanisms have been shown to have glycemic effects in human and animal models. Independent of weight loss, there are multiple mechanisms that may lead to amelioration or resolution of diabetes following bariatric surgery. There is abundant evidence pointing to changes in gut hormones, bile acids, gut microbiome, and intestinal nutrient sensing; more research is needed to clearly delineate their role in regulating energy and glucose homeostasis after bariatric surgery.
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MESH Headings
- Animals
- Bariatric Surgery
- Bile Acids and Salts/metabolism
- Biomarkers/blood
- Biomarkers/metabolism
- Diabetes Mellitus, Type 2/complications
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 2/physiopathology
- Diabetes Mellitus, Type 2/therapy
- Diet, Reducing
- Dysbiosis/complications
- Dysbiosis/etiology
- Dysbiosis/microbiology
- Dysbiosis/prevention & control
- Gastrointestinal Microbiome
- Humans
- Insulin Resistance
- Intestinal Mucosa/innervation
- Intestinal Mucosa/metabolism
- Intestinal Mucosa/microbiology
- Intestinal Mucosa/physiopathology
- Intestines/innervation
- Intestines/microbiology
- Intestines/physiopathology
- Neurons, Afferent/metabolism
- Neurons, Efferent/metabolism
- Obesity, Morbid/complications
- Obesity, Morbid/diet therapy
- Obesity, Morbid/physiopathology
- Obesity, Morbid/surgery
- Weight Loss
- Weight Reduction Programs
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Affiliation(s)
- Caroline A Andrew
- Comprehensive Weight Control Center, Division of Endocrinology, Diabetes & Metabolism, Weill Cornell Medical College, 1165 York Avenue, New York, NY, 10065, USA
| | - Devika Umashanker
- Comprehensive Medical Weight Management, Department of Bariatric Surgery, Hartford HealthCare Medical Group, Hartford, CT, USA
| | - Louis J Aronne
- Comprehensive Weight Control Center, Division of Endocrinology, Diabetes & Metabolism, Weill Cornell Medical College, 1165 York Avenue, New York, NY, 10065, USA
| | - Alpana P Shukla
- Comprehensive Weight Control Center, Division of Endocrinology, Diabetes & Metabolism, Weill Cornell Medical College, 1165 York Avenue, New York, NY, 10065, USA.
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50
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Gagnon C, Schafer AL. Bone Health After Bariatric Surgery. JBMR Plus 2018; 2:121-133. [PMID: 30283897 PMCID: PMC6124196 DOI: 10.1002/jbm4.10048] [Citation(s) in RCA: 126] [Impact Index Per Article: 18.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/24/2017] [Revised: 03/13/2018] [Accepted: 03/26/2018] [Indexed: 02/06/2023] Open
Abstract
Bariatric surgery results in long-term weight loss and improvement or resolution in obesity-related comorbidities. However, mounting evidence indicates that it adversely affects bone health. This review summarizes clinical research findings about the impact of bariatric surgery on skeletal outcomes. The literature is the largest and strongest for the Roux-en-Y gastric bypass (RYGB) procedure, as RYGB was the most commonly performed bariatric procedure worldwide until it was very recently overtaken by the sleeve gastrectomy (SG). Because SG is a newer procedure, its skeletal effects have not yet been well defined. Epidemiologic studies have now demonstrated an increased risk of fracture after RYGB and biliopancreatic diversion with duodenal switch, both of which include a malabsorptive component. As these epidemiologic data have emerged, patient-oriented studies have elucidated the bone tissue-level changes that may account for the heightened skeletal fragility. Bariatric surgery induces early and dramatic increases in biochemical markers of bone turnover. A notable feature of recent patient-oriented clinical studies is the application of advanced skeletal imaging modalities; studies address the limitations of dual-energy X-ray absorptiometry (DXA) by using quantitative computed tomography (QCT)-based modalities to examine volumetric bone mineral density and compartment-specific density and microstructure. RYGB results in pronounced declines in bone mass at the axial skeleton demonstrated by DXA and QCT, as well as at the appendicular skeleton demonstrated by high-resolution peripheral quantitative computed tomography (HR-pQCT). RYGB has detrimental effects on trabecular and cortical microarchitecture and estimated bone strength. Skeletal changes after RYGB appear early and continue even after weight loss plateaus and weight stabilizes. The skeletal effects of bariatric surgery are presumably multifactorial, and mechanisms may involve nutritional factors, mechanical unloading, hormonal factors, and changes in body composition and bone marrow fat. Clinical guidelines address bone health and may mitigate the negative skeletal effects of surgery, although more research is needed to direct and support such guidelines. © 2018 The Authors. JBMR Plus is published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.
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Affiliation(s)
- Claudia Gagnon
- Department of MedicineUniversité LavalQuebec CityCanada
- Endocrinology and Nephrology UnitCHU de Quebec Research CentreQuebec CityCanada
- Institute of Nutrition and Functional FoodsUniversité LavalQuebec CityCanada
- Quebec Heart and Lung Institute Research CentreQuébec CityCanada
| | - Anne L Schafer
- Department of MedicineUniversity of CaliforniaSan FranciscoCAUSA
- Department of Epidemiology and BiostatisticsUniversity of CaliforniaSan FranciscoCAUSA
- Endocrine Research UnitSan Francisco Veterans Affairs Heath Care SystemSan FranciscoCAUSA
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