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Zhou P, Li T, Zhao J, Al-Ansi W, Fan M, Qian H, Li Y, Wang L. Grain bound polyphenols: Molecular interactions, release characteristics, and regulation mechanisms of postprandial hyperglycemia. Food Res Int 2025; 208:116291. [PMID: 40263868 DOI: 10.1016/j.foodres.2025.116291] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2024] [Revised: 02/21/2025] [Accepted: 03/13/2025] [Indexed: 04/24/2025]
Abstract
Frequent postprandial hyperglycemia causes many chronic diseases. Grain polyphenols are widely recognized as natural active ingredients with high potential to treat chronic diseases due to their excellent postprandial hyperglycemic regulating effects. However, previous studies on polyphenols in grains mainly focused on the functional properties of free polyphenols and the extraction and physicochemical properties of bound polyphenols, ignoring the functional properties of bound polyphenols. Comprehensively understanding the binding properties of grain bound polyphenols (GBPs) and their mechanisms in regulating blood glucose levels is essential for developing and applying grain resources. This review summarizes the molecular interactions between GBPs and grain components and their effects on release characteristics and bioavailability at various stages. Meanwhile, the review focuses on elucidating the regulatory mechanism of post-release GBPs on postprandial hyperglycemia levels, incorporating insights from molecular docking, the gastrointestinal-brain axis, and gut flora. GBPs slow food digestion by occupying the active site of digestive enzymes and altering the secondary structure of enzymes and the hydrophobic environment of amino acid residues to inhibit enzyme activity. They modulate intestinal epithelial transport proteins (SGLT1, GLUT2, and GLUT4) to limit glucose absorption and increase glucose consumption. They also stimulate the release of short-term satiety hormones (CKK, GLP-1, and PYY) through the gastrointestinal-brain axis to decrease post-meal food intake. Furthermore, they optimize gut microbiota composition, promoting short-chain fatty acid production and bile acid metabolism. Therefore, developing functional foods with glucose-modulating properties based on GBPs is crucial for obesity prevention, diabetes management, and low-GI food development.
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Affiliation(s)
- Peng Zhou
- School of Food Science and Technology, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Tingting Li
- Department of Food Science and Engineering, College of Light Industry and Food Engineering, Nanjing Forestry University, Nanjing 210037, China
| | - Jiajia Zhao
- College of Cooking Science and Technology, Jiangsu College of Tourism, Yangzhou 225000, China
| | - Waleed Al-Ansi
- School of Food Science and Technology, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Mingcong Fan
- School of Food Science and Technology, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Haifeng Qian
- School of Food Science and Technology, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Yan Li
- School of Food Science and Technology, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China
| | - Li Wang
- School of Food Science and Technology, State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi 214122, China.
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Pabla P, Mallinson J, Nixon A, Keeton M, Cooper S, Marshall M, Jacques M, Brown S, Johansen OE, Cuenoud B, Karagounis LG, Tsintzas K. Effect of medium-chain triglycerides and whey protein isolate preloads on glycaemia in type 2 diabetes: a randomized crossover study. Am J Clin Nutr 2025; 121:232-245. [PMID: 39732398 PMCID: PMC11863336 DOI: 10.1016/j.ajcnut.2024.12.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2024] [Revised: 12/19/2024] [Accepted: 12/23/2024] [Indexed: 12/30/2024] Open
Abstract
BACKGROUND Small nutritional preloads can reduce postprandial glucose excursions in individuals with and without metabolic syndrome or type 2 diabetes (T2D). However, most studies have focused on preloads administered before single meals and have predominantly used protein-based preloads. OBJECTIVES To investigate the effects of sequential consumption of medium-chain triglycerides (MCT) and whey protein isolate (WPI) preloads before breakfast, lunch, and dinner on postprandial, diurnal, and 24-h glycaemia in individuals with T2D. METHODS Participants with T2D were studied over 3 randomized 24-h periods. They consumed either water before standardized breakfast, lunch, and dinner (CONTROL), 15 g MCT before breakfast and water before lunch and dinner (MCT), or 15 g MCT before breakfast and 10 g WPI before lunch and dinner (MCT + WPI). Diurnal (08:00-23:00 h) and 24 h (08:00-08:00 h) glycaemia (incremental AUC [iAUC]) and glycaemic variability (%coefficient of variation [%CV]) were evaluated by continuous glucose monitoring. Postprandial glycaemia (PPG) after breakfast and lunch was assessed by arterialized blood glucose iAUC. RESULTS In 21 enrolled patients (8 males/13 females, mean ± standard deviation age 55.1 ± 8.5 y, body mass index 31.7 ± 4.3 kg·m-2, glycated hemoglobin 59 ± 12 mmol·mol-1) diurnal and 24-h iAUC were similar across interventions, whereas 24-h %CV was lower in MCT (16.8 ± 0.8%, P = 0.033) and MCT + WPI (16.1 ± 0.9%, P = 0.0004) than CONTROL (18.7 ± 0.9%). PPG iAUC was ∼17% lower after breakfast in MCT and MCT + WPI compared with CONTROL, but only the MCT + WPI lowered glucose by 20% (P = 0.002) over the entire day (08:30-17:30 h). Gastric inhibitory polypeptide (GIP) (P = 0.00004), peptide YY (PYY) (P = 0.01), and β-hydroxybutyrate (P = 0.0001) were higher in MCT and MCT + WPI than CONTROL. Subjective appetite ratings were lower after breakfast and lunch in MCT + WPI (P = 0.001). CONCLUSIONS Sequential consumption of MCT and WPI preloads did not affect diurnal or 24-h glycaemia but lowered PPG and 24-h glycaemic variability in individuals with T2D. These effects were associated with increased circulating β-hydroxybutyrate, PYY, and GIP, and suppression of appetite. This trial was registered at clinicaltrials.gov as NCT04905589 (https://clinicaltrials.gov/study/NCT04905589).
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Affiliation(s)
- Pardeep Pabla
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | - Joanne Mallinson
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | - Aline Nixon
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | - Mia Keeton
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | - Scott Cooper
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | - Melanie Marshall
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | - Matthew Jacques
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | - Sara Brown
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom
| | | | | | - Leonidas G Karagounis
- Nestlé Health Science, Vevey, Switzerland; Mary MacKillop Institute for Health Research, Australian Catholic University, Melbourne, VIC, Australia; Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland
| | - Kostas Tsintzas
- MRC Versus Arthritis Centre for Musculoskeletal Ageing Research, School of Life Sciences, University of Nottingham, Queen's Medical Centre, Nottingham, United Kingdom.
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Eriksson SE, Maurer N, Zheng P, Sarici IS, DeWitt A, Riccardi M, Jobe BA, Ayazi S. Impact of Objective Colonic and Whole Gut Motility Data as Measured by Wireless Motility Capsule on Outcomes of Antireflux Surgery. J Am Coll Surg 2023; 236:305-315. [PMID: 36648258 PMCID: PMC9835684 DOI: 10.1097/xcs.0000000000000470] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 09/06/2022] [Accepted: 09/13/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND Studies show higher rates of dissatisfaction with antireflux surgery (ARS) outcomes in patients with chronic constipation. This suggests a relationship between colonic dysmotility and suboptimal surgical outcome. However, due to limitations in technology, there is no objective data available examining this relationship. The wireless motility capsule (WMC) is a novel technology consisting of an ingestible capsule equipped with pH, temperature, and pressure sensors, which provide information regarding regional and whole gut transit times, pH and motility. The aim of this study was to assess the impact of objective regional and whole gut motility data on the outcomes of ARS. STUDY DESIGN This was a retrospective review of patients who underwent WMC testing before ARS. Transit times, motility, and pH data obtained from different gastrointestinal tract regions were used in analysis to determine factors that impact surgical outcome. A favorable outcome was defined as complete resolution of the predominant reflux symptom and freedom from antisecretory medications. RESULTS The final study population consisted of 48 patients (fundoplication [n = 29] and magnetic sphincter augmentation [n = 19]). Of those patients, 87.5% were females and the mean age ± SD was 51.8 ± 14.5 years. At follow-up (mean ± SD, 16.8 ± 13.2 months), 87.5% of all patients achieved favorable outcomes. Patients with unfavorable outcomes had longer mean whole gut transit times (92.0 hours vs 55.7 hours; p = 0.024) and colonic transit times (78.6 hours vs 47.3 hours; p = 0.028), higher mean peak colonic pH (8.8 vs 8.15; p = 0.009), and higher mean antral motility indexes (310 vs 90.1; p = 0.050). CONCLUSIONS This is the first study to demonstrate that objective colonic dysmotility leads to suboptimal outcomes after ARS. WMC testing can assist with preoperative risk assessment and counseling for patients seeking ARS.
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Affiliation(s)
- Sven E Eriksson
- From the Esophageal Institute, Allegheny Health Network, Pittsburgh, PA
| | - Nicole Maurer
- From the Esophageal Institute, Allegheny Health Network, Pittsburgh, PA
| | - Ping Zheng
- From the Esophageal Institute, Allegheny Health Network, Pittsburgh, PA
| | - Inanc S Sarici
- From the Esophageal Institute, Allegheny Health Network, Pittsburgh, PA
| | - Ann DeWitt
- From the Esophageal Institute, Allegheny Health Network, Pittsburgh, PA
| | - Margaret Riccardi
- From the Esophageal Institute, Allegheny Health Network, Pittsburgh, PA
| | - Blair A Jobe
- From the Esophageal Institute, Allegheny Health Network, Pittsburgh, PA
- the Department of Surgery, Drexel University, Philadelphia, PA (Jobe, Ayazi)
| | - Shahin Ayazi
- From the Esophageal Institute, Allegheny Health Network, Pittsburgh, PA
- the Department of Surgery, Drexel University, Philadelphia, PA (Jobe, Ayazi)
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Jenkins B, Calder PC, Marino LV. A scoping review considering potential biomarkers or functional measures of gastrointestinal dysfunction and enteral feeding intolerance in critically ill adults. Clin Nutr ESPEN 2022; 52:331-339. [PMID: 36513473 DOI: 10.1016/j.clnesp.2022.09.014] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/17/2022] [Revised: 09/13/2022] [Accepted: 09/14/2022] [Indexed: 01/28/2023]
Abstract
BACKGROUND & AIM Enteral feeding intolerance (EFI) as a result of gastrointestinal (GI) dysfunction in critically ill adults can lead to suboptimal nutritional delivery, increasing the risk of hospital acquired malnutrition. There are no validated measures of EFI or consensus as to which measures could be used to define EFI. The aim of this scoping review is to explore the validity of biomarkers, physiological or functional measures of GI dysfunction and EFI in critically ill adults characterising their use in routine clinical practice to identify those with GI dysfunction to better guide nutritional support. METHODS Database searches were completed in Ovid MEDLINE, Embase, CINAHL and Web of Science using the Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR) guidelines. The search was performed until June 2022. Articles were included if they reported original studies that identify potential biomarkers or functional measures of EFI in critically ill adults. A nine-stage process was completed to extract and complete data synthesis. RESULTS 139 unique articles were identified. Following review of titles and abstracts, 114 of these articles were excluded, three further articles were excluded after full text review and 22 articles met the inclusion criteria. A thematic analysis of the articles included identified three overarching themes of GI dysfunction: (1) Serum biomarkers, (2) Physiological markers, and (3) Functional markers. Within the category of serum biomarkers, a further three sub-categories were identified: (i) enterohormones, (ii) markers of enterocyte function, and iii) cytokines and neurotransmitters. Some associations were seen between EFI and heparin binding protein, intra-abdominal pressure, cholecystokinin and acetylcholine levels but no markers are currently suitable for daily clinical use. CONCLUSIONS Further larger studies are required to characterise the relationships between serum biomarkers, physiological and functional makers of GI dysfunction in critically ill adults. A robust definition of GI dysfunction should be included in any future research.
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Affiliation(s)
- Bethan Jenkins
- Department of Dietetics/SLT, University Hospital Southampton NHS Foundation Trust, Southampton, UK; NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK.
| | - Philip C Calder
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK; School of Human Development and Health, Faculty of Medicine, University of Southampton, Southampton, UK
| | - Luise V Marino
- NIHR Southampton Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust and University of Southampton, Southampton, UK; Paediatric Intensive Care Unit, Southampton Children's Hospital, University Hospital Southampton NHS Foundation Trust, Southampton, UK; School of Health Sciences, Faculty of Environmental and Life Sciences, University of Southampton, Southampton, UK
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Camacho-Ramírez A, Prada-Oliveira JA, Ribelles-García A, Almorza-Gomar D, Pérez-Arana GM. The Leading Role of Peptide Tyrosine Tyrosine in Glycemic Control After Roux-en-Y Gastric Bypass in Rats. Obes Surg 2021; 30:697-706. [PMID: 31701411 DOI: 10.1007/s11695-019-04239-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
AIMS Roux-en-Y gastric bypass (RYGB) is one of the most effective surgical therapies for the rapid resolution of type 2 diabetes. However, the mechanisms underlying the entero-hormonal response after surgery and the role of peptide tyrosine tyrosine (PYY) in the restoration of normoglycemia are still not clear. METHODS We reproduced the RYGB technique in Wistar and Goto-Kakizaki rats and performed serum hormonal, histological, and hormonal-infusion test. RESULTS Using the diabetic Goto-Kakizaki (GK) rat model, we demonstrated that PYY plasma levels showed a remarkable peak approximately 30 min earlier than GLP-1 or GIP after mixed-meal administration in RYGB-operated rats with PYY. The GLP-1 and GIP areas under the curve (AUCs) increased after RYGB in GK rats. Additionally, the findings suggested that PYY (3-36) infusion led to increased GLP-1 and GIP plasma levels close to those obtained after a meal. Finally, the number of GLP-1-positive cells appeared to increase in the three segments of the small intestine in GK-RYGB-operated rats beyond the early presence of nutrient stimulation in the ileum. Nevertheless, PYY-positive cell numbers appeared to increase only in the ileum. CONCLUSION At least in rats, these data demonstrate an earlier essential role for PYY in gut hormone regulation after RYGB. We understand that PYY contributes to GLP-1 and GIP release and there must be the existence of enteroendocrine communication routes between the distal and proximal small intestine.
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Affiliation(s)
- Alonso Camacho-Ramírez
- Puerta del Mar Hospital, University of Cadiz, Cadiz, Spain.,Asociación Gaditana de Apoyo al Investigador, Cadiz, Spain.,Biomedical Science Research and Innovation Institute (INIBICA), University of Cadiz, Cadiz, Spain
| | - J Arturo Prada-Oliveira
- Asociación Gaditana de Apoyo al Investigador, Cadiz, Spain.,Biomedical Science Research and Innovation Institute (INIBICA), University of Cadiz, Cadiz, Spain.,Department of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, Plaza Fragela s/n, 11003, Cadiz, Spain
| | - Antonio Ribelles-García
- Department of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, Plaza Fragela s/n, 11003, Cadiz, Spain.,Sustainable Social Development Research Institute (INDESS), University of Cadiz, Cadiz, Spain
| | - David Almorza-Gomar
- Biomedical Science Research and Innovation Institute (INIBICA), University of Cadiz, Cadiz, Spain.,Operative Statistic and Research Department, University of Cadiz, Cadiz, Spain
| | - Gonzalo M Pérez-Arana
- Asociación Gaditana de Apoyo al Investigador, Cadiz, Spain. .,Biomedical Science Research and Innovation Institute (INIBICA), University of Cadiz, Cadiz, Spain. .,Department of Human Anatomy and Embryology, Faculty of Medicine, University of Cadiz, Plaza Fragela s/n, 11003, Cadiz, Spain.
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Schalla MA, Taché Y, Stengel A. Neuroendocrine Peptides of the Gut and Their Role in the Regulation of Food Intake. Compr Physiol 2021; 11:1679-1730. [PMID: 33792904 DOI: 10.1002/cphy.c200007] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
The regulation of food intake encompasses complex interplays between the gut and the brain. Among them, the gastrointestinal tract releases different peptides that communicate the metabolic state to specific nuclei in the hindbrain and the hypothalamus. The present overview gives emphasis on seven peptides that are produced by and secreted from specialized enteroendocrine cells along the gastrointestinal tract in relation with the nutritional status. These established modulators of feeding are ghrelin and nesfatin-1 secreted from gastric X/A-like cells, cholecystokinin (CCK) secreted from duodenal I-cells, glucagon-like peptide 1 (GLP-1), oxyntomodulin, and peptide YY (PYY) secreted from intestinal L-cells and uroguanylin (UGN) released from enterochromaffin (EC) cells. © 2021 American Physiological Society. Compr Physiol 11:1679-1730, 2021.
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Affiliation(s)
- Martha A Schalla
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany
| | - Yvette Taché
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, CURE: Digestive Diseases Research Center, David Geffen School of Medicine, UCLA, Los Angeles, California, USA.,VA Greater Los Angeles Healthcare System, Los Angeles, California, USA
| | - Andreas Stengel
- Charité Center for Internal Medicine and Dermatology, Department for Psychosomatic Medicine, Charité-Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, Berlin Institute of Health, Berlin, Germany.,Department of Psychosomatic Medicine and Psychotherapy, Medical University Hospital Tübingen, Tübingen, Germany
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Abstract
This review evaluates published studies regarding alpha-melanocyte stimulating hormone (α-MSH) in ghrelin-elicited feeding and gut motility. We have sought to integrate all available evidences to provide a complete review on the properties of melanocortin receptors (MCR) and the potential clinical treatment of α-MSH after ghrelin-elicited feeding and gut motility. The available studies were grouped into four categories: food intake, gastric emptying, small intestinal transit, and colonic transit. As we describe, the literature provides evidence of the ability of ghrelin to increase food intake, gastric emptying, small intestinal transit, and colonic transit. α-MSH, which displays high affinity for the MC3 and MC4 receptors, can competitively activate MCRs with agouti-related protein stimulated by ghrelin, and partly attenuates the effect of acyl ghrelin on food intake. Central ghrelin-induced acceleration of gastric emptying is not mediated by MCRs, but the acceleration of the small intestinal transit is at least partly mediated via MCRs in the brain. Similar to fecal pellets and total fecal weight, distal colonic motility and secretion are partly mediated by MCRs in the brain. The interplay between acyl ghrelin and MCRs may provide a new therapeutic avenue to ameliorate anorexia and constipation.
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Affiliation(s)
- Hsien-Hao Huang
- Department of Emergency Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Institute of Emergency and Critical Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
| | - Chih-Yen Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
- Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan, ROC
- Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan, ROC
- Chinese Taipei Society for the Study of Obesity, Taipei, Taiwan, ROC
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8
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Ng QX, Soh AYS, Loke W, Venkatanarayanan N, Lim DY, Yeo WS. Systematic review with meta-analysis: The association between post-traumatic stress disorder and irritable bowel syndrome. J Gastroenterol Hepatol 2019; 34:68-73. [PMID: 30144372 DOI: 10.1111/jgh.14446] [Citation(s) in RCA: 88] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2018] [Revised: 08/04/2018] [Accepted: 08/06/2018] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIM Post-traumatic stress disorder (PTSD) is a psychiatric condition characterized by symptoms of hyperarousal and hypervigilance. Increasing research on the "gut-brain" axis (bidirectional signaling between the gut and the brain) has drawn links between PTSD and irritable bowel syndrome (IBS), an exceedingly common yet incompletely understood gastrointestinal condition. This meta-analysis thus aimed to examine the body of evidence and extent of association of PTSD with IBS. METHODS Using the keywords [early abuse OR childhood abuse OR violence OR trauma OR PTSD] AND [irritable bowel syndrome or IBS], a preliminary search on the PubMed, Medline, Embase, ScienceDirect, PsychINFO, Web of Science, and Google Scholar databases yielded 11,257 papers published in English between January 1, 1988, and May 1, 2018. Of these, only eight studies were included in the final meta-analysis. RESULTS The eight studies (four cross-sectional and four cohort) contained a total of 648,375 subjects. Most studies were from the USA and conducted on army veterans. The funnel plot revealed a roughly symmetrical distribution of studies, and Egger test was not significant for publication bias (P = 0.583). Random-effects meta-analysis found PTSD to be a significant risk factor for IBS (pooled odds ratio 2.80, 95% confidence interval: 2.06 to 3.54, P < 0.001). CONCLUSIONS Overall, PTSD is associated with an increased likelihood of IBS. This is the first meta-analysis to specifically examine the association between PTSD and IBS, and it provides insights into the probable (patho)physiology and management of IBS, supporting a holistic consideration of the psychosocial aspects of IBS and further research into effective multi-modal therapeutics.
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Affiliation(s)
- Qin Xiang Ng
- National University Hospital, National University Health System, Singapore
- MOH Holdings Pte Ltd, Singapore
| | - Alex Yu Sen Soh
- National University Hospital, National University Health System, Singapore
| | | | | | | | - Wee-Song Yeo
- National University Hospital, National University Health System, Singapore
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9
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Melo-Duran D, Gonzalez-Ortiz G, Sola-Oriol D, Martinez-Mora M, Perez J, Bedford M. Relationship between peptide YY, cholecystokinin and fermentation products in fasted, re-fed and ad libitum fed broiler chickens. Anim Feed Sci Technol 2019. [DOI: 10.1016/j.anifeedsci.2018.11.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/21/2022]
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10
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Nesti L, Mengozzi A, Tricò D. Impact of Nutrient Type and Sequence on Glucose Tolerance: Physiological Insights and Therapeutic Implications. Front Endocrinol (Lausanne) 2019; 10:144. [PMID: 30906282 PMCID: PMC6418004 DOI: 10.3389/fendo.2019.00144] [Citation(s) in RCA: 34] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Accepted: 02/18/2019] [Indexed: 02/03/2023] Open
Abstract
Pharmacological and dietary interventions targeting postprandial glycemia have proved effective in reducing the risk for type 2 diabetes and its cardiovascular complications. Besides meal composition and size, the timing of macronutrient consumption during a meal has been recently recognized as a key regulator of postprandial glycemia. Emerging evidence suggests that premeal consumption of non-carbohydrate macronutrients (i.e., protein and fat "preloads") can markedly reduce postprandial glycemia by delaying gastric emptying, enhancing glucose-stimulated insulin release, and decreasing insulin clearance. The same improvement in glucose tolerance is achievable by optimal timing of carbohydrate ingestion during a meal (i.e., carbohydrate-last meal patterns), which minimizes the risk of body weight gain when compared with nutrient preloads. The magnitude of the glucose-lowering effect of preload-based nutritional strategies is greater in type 2 diabetes than healthy subjects, being comparable and additive to current glucose-lowering drugs, and appears sustained over time. This dietary approach has also shown promising results in pathological conditions characterized by postprandial hyperglycemia in which available pharmacological options are limited or not cost-effective, such as type 1 diabetes, gestational diabetes, and impaired glucose tolerance. Therefore, preload-based nutritional strategies, either alone or in combination with pharmacological treatments, may offer a simple, effective, safe, and inexpensive tool for the prevention and management of postprandial hyperglycemia. Here, we survey these novel physiological insights and their therapeutic implications for patients with diabetes mellitus and altered glucose tolerance.
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Affiliation(s)
- Lorenzo Nesti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Alessandro Mengozzi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Domenico Tricò
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
- Sant'Anna School of Advanced Studies, Institute of Life Sciences, Pisa, Italy
- *Correspondence: Domenico Tricò
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11
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Wijma RB, Emous M, van den Broek M, Laskewitz A, Kobold ACM, van Beek AP. Prevalence and pathophysiology of early dumping in patients after primary Roux-en-Y gastric bypass during a mixed-meal tolerance test. Surg Obes Relat Dis 2018; 15:73-81. [PMID: 30446401 DOI: 10.1016/j.soard.2018.10.004] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2018] [Revised: 09/19/2018] [Accepted: 10/05/2018] [Indexed: 01/10/2023]
Abstract
BACKGROUND Early dumping is a poorly defined and incompletely understood complication after Roux-en-Y gastric (RYGB). OBJECTIVE We performed a mixed-meal tolerance test in patients after RYGB to address the prevalence of early dumping and to gain further insight into its pathophysiology. SETTING The study was conducted in a regional hospital in the northern part of the Netherlands. METHODS From a random sample of patients who underwent primary RYGB between 2008 and 2011, 46 patients completed the mixed-meal tolerance test. The dumping severity score for early dumping was assessed every 30 minutes. A sum score at 30 or 60 minutes of ≥5 and an incremental score of ≥3 points were defined as indicating a high suspicion of early dumping. Blood samples were collected at baseline, every 10 minutes during the first half hour, and at 60 minutes after the start. RESULTS The prevalence of a high suspicion of early dumping was 26%. No differences were seen for absolute hematocrit value, inactive glucagon-like peptide-1, and vasoactive intestinal peptide between patients with or without early dumping. Patients at high suspicion of early dumping had higher levels of active glucagon-like peptide-1 and peptide YY. CONCLUSION The prevalence of complaints at high suspicion of early dumping in a random population of patients after RYGB is 26% in response to a mixed-meal tolerance test. Postprandial increases in both glucagon-like peptide-1 and peptide YY are associated with symptoms of early dumping, suggesting gut L-cell overactivity in this syndrome.
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Affiliation(s)
- Ragnhild B Wijma
- Department of Bariatric and Metabolic Surgery, Heelkunde Friesland Groep, Medical Center Leeuwarden, Leewarden, the Netherlands
| | - Marloes Emous
- Department of Bariatric and Metabolic Surgery, Heelkunde Friesland Groep, Medical Center Leeuwarden, Leewarden, the Netherlands.
| | - Merel van den Broek
- Department of Endocrinology, Medical Center Leeuwarden, Leewarden, the Netherlands
| | - Anke Laskewitz
- Certe Laboratories, Medical Center Leeuwarden, Leewarden, the Netherlands
| | - Anneke C Muller Kobold
- Department of Laboratory Medicine, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
| | - André P van Beek
- Department of Bariatric and Metabolic Surgery, Heelkunde Friesland Groep, Medical Center Leeuwarden, Leewarden, the Netherlands; Department of Endocrinology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands
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12
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Taylor AE, Bedford MR, Pace SC, Miller HM. The effects of phytase and xylanase supplementation on performance and egg quality in laying hens. Br Poult Sci 2018; 59:554-561. [PMID: 29855193 DOI: 10.1080/00071668.2018.1483575] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/14/2022]
Abstract
1. The aim of this study was to evaluate the effects of phytase and xylanase and their interaction on laying hen performance, egg quality, phosphorus (P) digestibility, phytate breakdown, volatile fatty acid (VFA) production and peptide YY concentration. 2. Two hundred and forty hens were allocated to cages at 22 weeks of age based on a 3 × 2 arrangement with phytase (0, 300 or 1500 FTU/kg) and xylanase (0 or 12 000 BXU/kg) as factors. 3. Phytase increased hen-day production (P < 0.05), daily egg mass (P < 0.05) and P digestibility with increasing levels of phytase (P < 0.001). Phytase fed at 1500 FTU/kg reduced IP6 and IP5 and increased myo-inositol concentration in gizzard digesta (P < 0.05). Phytase fed at 300 FTU/kg reduced IP6 in ileal digesta (P < 0.05); however, IP6 and IP5 were further reduced and myo-inositol increased when phytase was added at 1500 FTU/kg (P < 0.05). 4. Xylanase improved feed efficiency when phytase was fed at 300 FTU/kg (P < 0.05). In the absence of phytase, xylanase reduced dry matter and Ca digestibilities (P < 0.05). 5. Neither phytase nor xylanase had an effect on peptide YY or caecal VFA concentrations.
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Affiliation(s)
- A E Taylor
- a Faculty of Biological Sciences , University of Leeds , Leeds , UK
| | - M R Bedford
- b AB Vista Feed Ingredients Ltd , Marlborough , UK
| | - S C Pace
- a Faculty of Biological Sciences , University of Leeds , Leeds , UK
| | - H M Miller
- a Faculty of Biological Sciences , University of Leeds , Leeds , UK
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13
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Miller KE, Bajzer Ž, Hein SS, Phillips JE, Syed S, Wright AM, Cipriani G, Gibbons SJ, Szurszewski JH, Farrugia G, Ordog T, Linden DR. High temporal resolution gastric emptying breath tests in mice. Neurogastroenterol Motil 2018; 30:e13333. [PMID: 29575442 PMCID: PMC6157017 DOI: 10.1111/nmo.13333] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/27/2017] [Accepted: 02/11/2018] [Indexed: 12/13/2022]
Abstract
BACKGROUND Gastric emptying is a complex physiological process regulating the division of a meal into smaller partitions for the small intestine. Disrupted gastric emptying contributes to digestive disease, yet current measures may not reflect different mechanisms by which the process can be altered. METHODS We have developed high temporal resolution solid and liquid gastric emptying breath tests in mice using [13 C]-octanoic acid and off axis- integrated cavity output spectroscopy (OA-ICOS). Stretched gamma variate and 2-component stretched gamma variate models fit measured breath excretion data. KEY RESULTS These assays detect acceleration and delay using pharmacological (7.5 mg/kg atropine) or physiological (nutrients, cold exposure stress, diabetes) manipulations and remain stable over time. High temporal resolution resolved complex excretion curves with 2 components, which was more prevalent in mice with delayed gastric emptying following streptozotocin-induced diabetes. There were differences in the gastric emptying of Balb/c vs C57Bl6 mice, with slower gastric emptying and a greater occurrence of two-phase gastric emptying curves in the latter strain. Gastric emptying of C57Bl6 could be accelerated by halving the meal size, but with no effect on the occurrence of two-phase gastric emptying curves. A greater proportion of two-phase gastric emptying was induced in Balb/c mice with the administration of PYY (8-80 nmol) 60 min following meal ingestion. CONCLUSIONS AND INFERENCES Collectively, these results demonstrate the utility of high temporal resolution gastric emptying assays. Two-phase gastric emptying is more prevalent than previously reported, likely involves intestinal feedback, but contributes little to the overall rate of gastric emptying.
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Affiliation(s)
- Katie E. Miller
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
| | - Željko Bajzer
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
- Department of Biochemistry and Molecular Biology, Mayo Clinic
College of Medicine, Rochester, MN 55905 USA
| | - Stephanie S. Hein
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
| | - Jessica E. Phillips
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
| | - Sabriya Syed
- Biochemistry and Molecular Biology Graduate Program, Mayo Clinic
College of Medicine, Rochester, MN 55905 USA
| | - Alec M. Wright
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
| | - Gianluca Cipriani
- Division of Gastroenterology and Hepatology, Department of Medicine,
Mayo Clinic College of Medicine, Rochester, MN 55905 USA
| | - Simon J. Gibbons
- Division of Gastroenterology and Hepatology, Department of Medicine,
Mayo Clinic College of Medicine, Rochester, MN 55905 USA
| | - Joseph H. Szurszewski
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
- Division of Gastroenterology and Hepatology, Department of Medicine,
Mayo Clinic College of Medicine, Rochester, MN 55905 USA
| | - Gianrico Farrugia
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
- Division of Gastroenterology and Hepatology, Department of Medicine,
Mayo Clinic College of Medicine, Rochester, MN 55905 USA
| | - Tamas Ordog
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
- Division of Gastroenterology and Hepatology, Department of Medicine,
Mayo Clinic College of Medicine, Rochester, MN 55905 USA
| | - David R. Linden
- Department of Physiology and Biomedical Engineering and Enteric
NeuroScience Program, Mayo Clinic College of Medicine, Rochester MN 55905 USA
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14
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The effects of xylanase on grower pig performance, concentrations of volatile fatty acids and peptide YY in portal and peripheral blood. Animal 2018; 12:2499-2504. [PMID: 29508681 DOI: 10.1017/s1751731118000277] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/06/2022] Open
Abstract
Non-starch polysaccharides (NSP) present in wheat and barley can act as anti-nutrients leading to an increase in digesta viscosity and a reduction in nutrient digestibility. Xylanase, an NSP-degrading enzyme, has been shown to increase nutrient digestibility in pigs. The objectives of this study were: (1) to identify the optimum inclusion level of xylanase in grower pig diets by measuring the effect of increasing enzyme levels on growth performance, the concentration of volatile fatty acids (VFA) and peptide YY concentration in portal and peripheral blood of grower pigs and (2) to increase our understanding of the interrelationships between xylanase inclusion, VFA production and peptide YY secretion. A total of 512 grower pigs ((Large White×Landrace)×MAXGRO) were allocated to pens creating 32 replicates of four pigs per pen per treatment. Pigs were allocated to trial weighing 14.2±0.31 kg and remained on trial until ~41.5±3.31 kg. The experiment was a dose response design with four inclusion levels (0, 8000, 16 000 or 32 000 BXU/kg) of xylanase (Econase XT). Diets were cereal-based wheat, barley mix formulated to meet or exceed the nutrient requirements of grower pigs. Body weight and feed intake were recorded to calculate growth performance. Pen faecal samples were collected to estimate DM, organic matter (OM) and crude fibre (CF) apparent total-tract digestibility. At the end of the trial 16 pigs per treatment were euthanised by schedule 1 procedures. Peripheral and portal blood samples were collected for peptide YY and VFA analysis. The addition of xylanase to the diet had no effect on growth performance, DM, OM or CF total-tract digestibility; however, xylanase tended to have a quadratic effect on ileum pH with higher pH values recorded for pigs fed a diet supplemented with 8000 and 16 000 BXU/kg xylanase (P<0.1). Xylanase had no effect on peptide YY levels or VFA concentration. Total VFA concentration was higher in portal compared with peripheral blood (P<0.05). In conclusion, the addition of xylanase had no effect on grower pig performance, nutrient digestibility, VFA concentration or peptide YY concentration when fed up to 32 000 BXU/kg over a 35-day period. Pig performance was good for all treatments throughout the trial suggesting that diet quality was sufficient thus there were no beneficial effects of adding xylanase.
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15
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Huang HH, Chen LY, Doong ML, Chang SC, Chen CY. α-melanocyte stimulating hormone modulates the central acyl ghrelin-induced stimulation of feeding, gastrointestinal motility, and colonic secretion. DRUG DESIGN DEVELOPMENT AND THERAPY 2017; 11:2377-2386. [PMID: 28860709 PMCID: PMC5566386 DOI: 10.2147/dddt.s143749] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Background Acyl ghrelin-induced intake depends on hypothalamic neuropeptide Y and agouti-related protein (AgRP) neurotransmitters. Intracerebroventricular (ICV) injection of AgRP increases feeding through competitive antagonism at melanocortin receptors. ICV administration of α-melanocyte stimulating hormone (α-MSH), a natural antagonist of AgRP, may modulate the acyl ghrelin-induced orexigenic effect. Objective This study aimed to investigate the modulating effect of α-MSH on the central acyl ghrelin-induced food intake, gastrointestinal motility, and colonic secretion in rats. Methods and procedures We examined the effects of α-MSH and acyl ghrelin on food intake, gastric emptying, small intestinal transit, colonic motility, and secretion in conscious rats with a chronic implant of ICV catheters. Results ICV injection of O-n-octanoylated ghrelin (0.1 nmol/rat) significantly increased the cumulative food intake up to 8 h (P<0.01), enhanced non-nutrient semi-liquid gastric emptying (P<0.001), increased the geometric center and running percentage of small intestinal transit (P<0.001), accelerated colonic transit time (P<0.05), and increased fecal pellet output (P<0.01) and total fecal weight (P<0.01). Pretreatment with ICV injection of α-MSH (1.0 and 2.0 nmol/rat) attenuated the acyl ghrelin-induced hyperphagic effect, fecal pellet output, and total fecal weight, while higher dose of α-MSH (2.0 nmol/rat) attenuated the increase in the geometric center of small intestinal transit (P<0.01). However, neither dose of α-MSH altered acyl ghrelin-stimulated gastroprokinetic effect, increase in the running percentage of small intestinal transit, nor accelerated colonic transit time. Conclusion α-MSH is involved in central acyl ghrelin-elicited feeding, small intestinal transit, fecal pellet output, and fecal weight. α-MSH does not affect central acyl ghrelin-induced acceleration of gastric emptying and colonic transit time in rats.
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Affiliation(s)
- Hsien-Hao Huang
- Institute of Clinical Medicine, National Yang-Ming University of Medicine.,Department of Emergency Medicine, Taipei Veterans General Hospital
| | - Liang-Yu Chen
- Aging and Health Research Center, National Yang-Ming University.,Center for Geriatrics and Gerontology, Taipei Veterans General Hospital
| | - Ming-Luen Doong
- Institute of Physiology, National Yang-Ming University School of Medicine
| | - Shi-Chuan Chang
- Institute of Emergency and Critical Medicine, National Yang-Ming University School of Medicine.,Department of Chest Medicine, Taipei Veterans General Hospital
| | - Chih-Yen Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital.,Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei.,Taiwan Association for the Study of Small Intestinal Diseases, Guishan, Taiwan
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16
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Steinert RE, Feinle-Bisset C, Asarian L, Horowitz M, Beglinger C, Geary N. Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB. Physiol Rev 2017; 97:411-463. [PMID: 28003328 PMCID: PMC6151490 DOI: 10.1152/physrev.00031.2014] [Citation(s) in RCA: 402] [Impact Index Per Article: 50.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The efficacy of Roux-en-Y gastric-bypass (RYGB) and other bariatric surgeries in the management of obesity and type 2 diabetes mellitus and novel developments in gastrointestinal (GI) endocrinology have renewed interest in the roles of GI hormones in the control of eating, meal-related glycemia, and obesity. Here we review the nutrient-sensing mechanisms that control the secretion of four of these hormones, ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (GLP-1), and peptide tyrosine tyrosine [PYY(3-36)], and their contributions to the controls of GI motor function, food intake, and meal-related increases in glycemia in healthy-weight and obese persons, as well as in RYGB patients. Their physiological roles as classical endocrine and as locally acting signals are discussed. Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36). While CCK has been fully established as an endogenous endocrine control of eating in healthy-weight persons, the roles of all four hormones in eating in obese persons and following RYGB are uncertain. Similarly, only GLP-1 clearly contributes to the endocrine control of meal-related glycemia. It is likely that local signaling is involved in these hormones' actions, but methods to determine the physiological status of local signaling effects are lacking. Further research and fresh approaches are required to better understand ghrelin, CCK, GLP-1, and PYY(3-36) physiology; their roles in obesity and bariatric surgery; and their therapeutic potentials.
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Affiliation(s)
- Robert E Steinert
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Christine Feinle-Bisset
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Lori Asarian
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Michael Horowitz
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Christoph Beglinger
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
| | - Nori Geary
- University of Adelaide Discipline of Medicine and National Health and Medical Research Council of Australia Centre of Research Excellence in Translating Nutritional Science to Good Health, Adelaide, Australia; DSM Nutritional Products, R&D Human Nutrition and Health, Basel, Switzerland; Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland; Department of Biomedicine and Division of Gastroenterology, University Hospital Basel, Basel, Switzerland; and Department of Psychiatry, Weill Medical College of Cornell University, New York, New York
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17
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Jang KU, Yu CS, Lim SB, Park IJ, Yoon YS, Kim CW, Lee JL, Yang SK, Ye BD, Kim JC. Factors affecting poor nutritional status after small bowel resection in patients with Crohn disease. Medicine (Baltimore) 2016; 95:e4285. [PMID: 27472702 PMCID: PMC5265839 DOI: 10.1097/md.0000000000004285] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/18/2016] [Revised: 06/23/2016] [Accepted: 06/24/2016] [Indexed: 12/18/2022] Open
Abstract
In Crohn disease, bowel-preserving surgery is necessary to prevent short bowel syndrome due to repeated operations. This study aimed to determine the remnant small bowel length cut-off and to evaluate the clinical factors related to nutritional status after small bowel resection in Crohn disease.We included 394 patients (69.3% male) who underwent small bowel resection for Crohn disease between 1991 and 2012. Patients who were classified as underweight (body mass index < 17.5) or at high risk of nutrition-related problems (modified nutritional risk index < 83.5) were regarded as having a poor nutritional status. Preliminary remnant small bowel length cut-offs were determined using receiver operating characteristic curves. Variables associated with poor nutritional status were assessed retrospectively using Student t tests, chi-squared tests, Fisher exact tests, and logistic regression analyses.The mean follow-up period was 52.9 months and the mean patient ages at the time of the last bowel surgery and last follow-up were 31.2 and 35.7 years, respectively. The mean remnant small bowel length was 331.8 cm. Forty-three patients (10.9%) underwent ileostomy, 309 (78.4%) underwent combined small bowel and colon resection, 111 (28.2%) had currently active disease, and 105 (26.6%) underwent at least 2 operations for recurrent disease. The mean body mass index and modified nutritional risk index were 20.6 and 100.8, respectively. The independent factors affecting underweight status were remnant small bowel length ≤240 cm (odds ratio: 4.84, P < 0.001), ileostomy (odds ratio: 4.70, P < 0.001), and currently active disease (odds ratio: 4.16, P < 0.001). The independent factors affecting high nutritional risk were remnant small bowel length ≤230 cm (odds ratio: 2.84, P = 0.012), presence of ileostomy (odds ratio: 3.36, P = 0.025), and currently active disease (odds ratio: 4.90, P < 0.001).Currently active disease, ileostomy, and remnant small bowel length ≤230 cm are risk factors affecting the poor nutritional status of patients with Crohn disease after small bowel resection.
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Affiliation(s)
- Ki Ung Jang
- Department of Colorectal Surgery, University of Ulsan College of Medicine, Asan Medical Center
| | - Chang Sik Yu
- Department of Colorectal Surgery, University of Ulsan College of Medicine, Asan Medical Center
| | - Seok-Byung Lim
- Department of Colorectal Surgery, University of Ulsan College of Medicine, Asan Medical Center
| | - In Ja Park
- Department of Colorectal Surgery, University of Ulsan College of Medicine, Asan Medical Center
| | - Yong Sik Yoon
- Department of Colorectal Surgery, University of Ulsan College of Medicine, Asan Medical Center
| | - Chan Wook Kim
- Department of Colorectal Surgery, University of Ulsan College of Medicine, Asan Medical Center
| | - Jong Lyul Lee
- Department of Colorectal Surgery, University of Ulsan College of Medicine, Asan Medical Center
| | - Suk-Kyun Yang
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Byong Duk Ye
- Department of Gastroenterology, University of Ulsan College of Medicine, Asan Medical Center, Seoul, Republic of Korea
| | - Jin Cheon Kim
- Department of Colorectal Surgery, University of Ulsan College of Medicine, Asan Medical Center
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18
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Stefanidis A, Forrest N, Brown WA, Dixon JB, O’Brien PB, Juliane Kampe, Oldfield BJ. An investigation of the neural mechanisms underlying the efficacy of the adjustable gastric band. Surg Obes Relat Dis 2016; 12:828-838. [DOI: 10.1016/j.soard.2015.11.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2015] [Revised: 10/19/2015] [Accepted: 11/19/2015] [Indexed: 02/08/2023]
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Camilleri M. Peripheral mechanisms in appetite regulation. Gastroenterology 2015; 148:1219-33. [PMID: 25241326 PMCID: PMC4369188 DOI: 10.1053/j.gastro.2014.09.016] [Citation(s) in RCA: 155] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2014] [Revised: 09/09/2014] [Accepted: 09/15/2014] [Indexed: 12/13/2022]
Abstract
Peripheral mechanisms in appetite regulation include the motor functions of the stomach, such as the rate of emptying and accommodation, which convey symptoms of satiation to the brain. The rich repertoire of peripherally released peptides and hormones provides feedback from the arrival of nutrients in different regions of the gut from where they are released to exert effects on satiation, or regulate metabolism through their incretin effects. Ultimately, these peripheral factors provide input to the highly organized hypothalamic circuitry and vagal complex of nuclei to determine cessation of energy intake during meal ingestion, and the return of appetite and hunger after fasting. Understanding these mechanisms is key to the physiological control of feeding and the derangements that occur in obesity and their restoration with treatment (as shown by the effects of bariatric surgery).
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Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research, Mayo Clinic College of Medicine, Rochester, Minnesota.
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20
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Adam CL, Williams PA, Garden KE, Thomson LM, Ross AW. Dose-dependent effects of a soluble dietary fibre (pectin) on food intake, adiposity, gut hypertrophy and gut satiety hormone secretion in rats. PLoS One 2015; 10:e0115438. [PMID: 25602757 PMCID: PMC4300082 DOI: 10.1371/journal.pone.0115438] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/22/2014] [Accepted: 11/25/2014] [Indexed: 12/16/2022] Open
Abstract
Soluble fermentable dietary fibre elicits gut adaptations, increases satiety and potentially offers a natural sustainable means of body weight regulation. Here we aimed to quantify physiological responses to graded intakes of a specific dietary fibre (pectin) in an animal model. Four isocaloric semi-purified diets containing 0, 3.3%, 6.7% or 10% w/w apple pectin were offered ad libitum for 8 or 28 days to young adult male rats (n = 8/group). Measurements were made of voluntary food intake, body weight, initial and final body composition by magnetic resonance imaging, final gut regional weights and histology, and final plasma satiety hormone concentrations. In both 8- and 28-day cohorts, dietary pectin inclusion rate was negatively correlated with food intake, body weight gain and the change in body fat mass, with no effect on lean mass gain. In both cohorts, pectin had no effect on stomach weight but pectin inclusion rate was positively correlated with weights and lengths of small intestine and caecum, jejunum villus height and crypt depth, ileum crypt depth, and plasma total glucagon-like peptide-1 (GLP-1) and peptide tyrosine tyrosine (PYY) concentrations, and at 8 days was correlated with weight and length of colon and with caecal mucosal depth. Therefore, the gut's morphological and endocrine adaptations were dose-dependent, occurred within 8 days and were largely sustained for 28 days during continued dietary intervention. Increasing amounts of the soluble fermentable fibre pectin in the diet proportionately decreased food intake, body weight gain and body fat content, associated with proportionately increased satiety hormones GLP-1 and PYY and intestinal hypertrophy, supporting a role for soluble dietary fibre-induced satiety in healthy body weight regulation.
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Affiliation(s)
- Clare L. Adam
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
| | - Patricia A. Williams
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
| | - Karen E. Garden
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
| | - Lynn M. Thomson
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
| | - Alexander W. Ross
- Ingestive Behaviour Group, Obesity & Metabolic Health Division, Rowett Institute of Nutrition & Health, University of Aberdeen, Aberdeen AB21 9SB, Scotland, United Kingdom
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Abstract
BACKGROUND Bariatric surgical procedures are classified by their presumed mechanisms of action: restrictive, malabsorptive or a combination of both. However, this dogma is questionable and remains unproven. We investigated post-operative changes in nutrient absorption and transit time following bariatric surgery. METHODS Participants were recruited into four groups: obese controls (body mass index (BMI) >30 kg/m2, n = 7), adjustable gastric banding (n = 6), Roux-en-Y gastric bypass (RYGB, n = 7) and biliopancreatic diversion with duodenal switch (DS, n = 5). Participants underwent sulphasalazine/sulphapyridine tests (oro-caecal transit time); fasting plasma citrulline (functional enterocyte mass); 3 days faecal collection for faecal elastase 1 (FE-1); calprotectin (FCp); faecal fatty acids (pancreatic exocrine function, gut inflammation and fat excretion, respectively); and 5 h D-xylose, L-rhamnose and lactulose test (intestinal absorption and permeability). RESULTS Age and gender were not different but BMI differed between groups (p = 0.001). No difference in oro-caecal transit time (p = 0.935) or functional enterocyte mass (p = 0.819) was detected. FCp was elevated post-RYGB vs. obese (p = 0.016) and FE-1 was reduced post-RYGB vs. obese (p = 0.002). Faecal fat concentrations were increased post-DS vs. obese (p = 0.038) and RYGB (p = 0.024) and were also higher post-RYGB vs. obese (p = 0.033). Urinary excretion of D-xylose and L-rhamnose was not different between the groups; however, lactulose/rhamnose ratio was elevated post-DS vs. other groups (all p < 0.02), suggesting increased intestinal permeability. CONCLUSIONS Following RYGB, there are surprisingly few abnormalities or indications of severe malabsorption of fats or sugars. Small bowel adaptation after bariatric surgery may be key to understanding the mechanisms responsible for the beneficial metabolic effects of these operations.
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22
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Goldstone AP, Prechtl CG, Scholtz S, Miras AD, Chhina N, Durighel G, Deliran SS, Beckmann C, Ghatei MA, Ashby DR, Waldman AD, Gaylinn BD, Thorner MO, Frost GS, Bloom SR, Bell JD. Ghrelin mimics fasting to enhance human hedonic, orbitofrontal cortex, and hippocampal responses to food. Am J Clin Nutr 2014; 99:1319-30. [PMID: 24760977 PMCID: PMC6410902 DOI: 10.3945/ajcn.113.075291] [Citation(s) in RCA: 105] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/10/2013] [Accepted: 03/05/2014] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Ghrelin, which is a stomach-derived hormone, increases with fasting and energy restriction and may influence eating behaviors through brain hedonic reward-cognitive systems. Therefore, changes in plasma ghrelin might mediate counter-regulatory responses to a negative energy balance through changes in food hedonics. OBJECTIVE We investigated whether ghrelin administration (exogenous hyperghrelinemia) mimics effects of fasting (endogenous hyperghrelinemia) on the hedonic response and activation of brain-reward systems to food. DESIGN In a crossover design, 22 healthy, nonobese adults (17 men) underwent a functional magnetic resonance imaging (fMRI) food-picture evaluation task after a 16-h overnight fast (Fasted-Saline) or after eating breakfast 95 min before scanning (730 kcal, 14% protein, 31% fat, and 55% carbohydrate) and receiving a saline (Fed-Saline) or acyl ghrelin (Fed-Ghrelin) subcutaneous injection before scanning. One male subject was excluded from the fMRI analysis because of excess head motion, which left 21 subjects with brain-activation data. RESULTS Compared with the Fed-Saline visit, both ghrelin administration to fed subjects (Fed-Ghrelin) and fasting (Fasted-Saline) significantly increased the appeal of high-energy foods and associated orbitofrontal cortex activation. Both fasting and ghrelin administration also increased hippocampus activation to high-energy- and low-energy-food pictures. These similar effects of endogenous and exogenous hyperghrelinemia were not explicable by consistent changes in glucose, insulin, peptide YY, and glucagon-like peptide-1. Neither ghrelin administration nor fasting had any significant effect on nucleus accumbens, caudate, anterior insula, or amygdala activation during the food-evaluation task or on auditory, motor, or visual cortex activation during a control task. CONCLUSIONS Ghrelin administration and fasting have similar acute stimulatory effects on hedonic responses and the activation of corticolimbic reward-cognitive systems during food evaluations. Similar effects of recurrent or chronic hyperghrelinemia on an anticipatory food reward may contribute to the negative impact of skipping breakfast on dietary habits and body weight and the long-term failure of energy restriction for weight loss.
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Affiliation(s)
- Anthony P Goldstone
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Christina G Prechtl
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Samantha Scholtz
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Alexander D Miras
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Navpreet Chhina
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Giuliana Durighel
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Seyedeh S Deliran
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Christian Beckmann
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Mohammad A Ghatei
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Damien R Ashby
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Adam D Waldman
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Bruce D Gaylinn
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Michael O Thorner
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Gary S Frost
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Stephen R Bloom
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
| | - Jimmy D Bell
- From the Metabolic and Molecular Imaging Group (APG, CGP, SS, ADM, NC, SSD, and JDB) and Robert Steiner MRI Unit (GD), Medical Research Council Clinical Sciences Centre, the Computational, Cognitive and Clinical Neuroimaging Laboratory, Division of Brain Sciences (CB), the Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism (MAG, DRA, GSF, and SRB), and the Division of Brain Sciences (ADW), Imperial College London, Hammersmith Hospital, London, United Kingdom, and the Department of Endocrinology, University of Virginia, Charlottesville, VA (BDG and MOT)
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Acosta A, Abu Dayyeh BK, Port JD, Camilleri M. Recent advances in clinical practice challenges and opportunities in the management of obesity. Gut 2014; 63:687-95. [PMID: 24402654 PMCID: PMC4170188 DOI: 10.1136/gutjnl-2013-306235] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Despite advances in understanding the roles of adiposity, food intake, GI and adipocyte-related hormones, inflammatory mediators, the gut-brain axis and the hypothalamic nervous system in the pathophysiology of obesity, the effects of different therapeutic interventions on those pathophysiological mechanisms are controversial. There are still no low-cost, safe, effective treatments for obesity and its complications. Currently, bariatric surgical approaches targeting the GI tract are more effective than non-surgical approaches in inducing weight reduction and resolving obesity-related comorbidities. However, current guidelines emphasise non-surgical approaches through lifestyle modification and medications to achieve slow weight loss, which is not usually sustained and may be associated with medication-related side effects. This review analyses current central, peripheral or hormonal targets to treat obesity and addresses challenges and opportunities to develop novel approaches for obesity.
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Affiliation(s)
- Andres Acosta
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Barham K. Abu Dayyeh
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - John D. Port
- Division of Neuroradiology, Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
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Akhavan T, Luhovyy BL, Panahi S, Kubant R, Brown PH, Anderson GH. Mechanism of action of pre-meal consumption of whey protein on glycemic control in young adults. J Nutr Biochem 2013; 25:36-43. [PMID: 24314863 DOI: 10.1016/j.jnutbio.2013.08.012] [Citation(s) in RCA: 100] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/12/2013] [Revised: 08/27/2013] [Accepted: 08/30/2013] [Indexed: 12/13/2022]
Abstract
Whey protein (WP), when consumed in small amounts prior to a meal, improves post-meal glycemic control more than can be explained by insulin-dependent mechanisms alone. The objective of the study was to identify the mechanism of action of WP beyond insulin on the reduction of post-meal glycemia. In a randomized crossover study, healthy young men received preloads (300 ml) of WP (10 and 20 g), glucose (10 and 20 g) or water (control). Paracetamol (1.5 g) was added to the preloads to measure gastric emptying. Plasma concentrations of paracetamol, glucose, and β-cell and gastrointestinal hormones were measured before preloads (baseline) and at intervals before (0-30 min) and after (50-230 min) a preset pizza meal (12 kcal/kg). Whey protein slowed pre-meal gastric emptying rate compared to the control and 10 g glucose (P<.0001), and induced lower pre-meal insulin and C-peptide than the glucose preloads (P<.0001). Glucose, but not WP, increased pre-meal plasma glucose concentrations (P<.0001). Both WP and glucose reduced post-meal glycemia (P=.0006) and resulted in similar CCK, amylin, ghrelin and GIP responses (P<.05). However, compared with glucose, WP resulted in higher post-meal GLP-1 and peptide tyrosine-tyrosine (PYY) and lower insulin concentrations, without altering insulin secretion and extraction rates. For the total duration of this study (0-230 min), WP resulted in lower mean plasma glucose, insulin and C-peptide, but higher GLP-1 and PYY concentrations than the glucose preloads. In conclusion, pre-meal consumption of WP lowers post-meal glycemia by both insulin-dependent and insulin-independent mechanisms.
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Affiliation(s)
- Tina Akhavan
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada
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25
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Abnormal plasma peptide YY(3-36) levels in patients with liver cirrhosis. Nutrition 2012; 27:880-4. [PMID: 21819934 DOI: 10.1016/j.nut.2010.12.013] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/26/2010] [Revised: 12/14/2010] [Accepted: 12/14/2010] [Indexed: 12/18/2022]
Abstract
OBJECTIVE Peptide YY(3-36) (PYY(3-36)) is a gut hormone with anorectic action that also affects energy expenditure. Anorexia and malnutrition are often observed in patients with decompensated liver cirrhosis (LC), whereas patients with LC after insertion of transjugular portosystemic stent shunts (TIPS) show normal eating behavior. The underlying mechanism of anorexia in decompensated LC and its resolution in patients with TIPS is still unclear. We thus investigated fasting and postprandial PYY(3-36) serum levels in patients with decompensated LC, patients with compensated LC with in situ TIPS, and healthy controls. METHODS We analyzed fasting PYY(3-36) levels in six patients with decompensated LC (four men and two women, 55 ± 11 y of age), nine patients with TIPS (seven men and two women, 48 ± 11 y of age), and 10 controls (eight men and two women, 43 ± 9 y of age) postprandially after a standardized meal of 300 kcal and during 1-h continuous parenteral nutrition. Energy expenditure was determined by indirect calorimetry. RESULTS At baseline PYY(3-36) was comparable in controls and patients with TIPS (91 ± 10 and 89 ± 25 ng/L) but was increased in patients with decompensated LC (165 ± 44 ng/L, P < 0.01). Although the cumulative postprandial PYY(3-36) increase was similar in controls (mean 2089 ng/240 min per liter) and patients with decompensated LC (mean 1735 ng/240 min per liter), no postprandial PYY(3-36) increase was observed in patients with TIPS (mean -579 ng/240 min per liter). Parenteral nutrition did not significantly affect PYY(3-36) levels in any group. Fasting PYY(3-36) values were negatively related to resting energy expenditure (r = -0.443, P = 0.030). PYY(3-36) was not associated to liver parameters (e.g., bilirubin, alanine aminotransferase). CONCLUSION Our results demonstrate an abnormal neuroendocrine regulation of PYY(3-36) in patients with decompensated LC and those with TIPS.
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Little TJ, Feinle-Bisset C. Effects of dietary fat on appetite and energy intake in health and obesity — Oral and gastrointestinal sensory contributions. Physiol Behav 2011; 104:613-20. [DOI: 10.1016/j.physbeh.2011.04.038] [Citation(s) in RCA: 85] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2011] [Revised: 04/15/2011] [Accepted: 04/26/2011] [Indexed: 02/08/2023]
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27
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Vermeulen MA, Richir MC, Garretsen MK, van Schie A, Ghatei MA, Holst JJ, Heijboer AC, Uitdehaag BM, Diamant M, Eekhoff EMW, van Leeuwen PA, Ligthart-Melis GC. Gastric emptying, glucose metabolism and gut hormones: Evaluation of a common preoperative carbohydrate beverage. Nutrition 2011; 27:897-903. [DOI: 10.1016/j.nut.2010.10.001] [Citation(s) in RCA: 13] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2010] [Accepted: 10/07/2010] [Indexed: 12/13/2022]
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Li J, Ma W, Wang S. Slower gastric emptying in high-fat diet induced obese rats is associated with attenuated plasma ghrelin and elevated plasma leptin and cholecystokinin concentrations. ACTA ACUST UNITED AC 2011; 171:53-7. [PMID: 21784108 DOI: 10.1016/j.regpep.2011.07.004] [Citation(s) in RCA: 38] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2011] [Revised: 06/03/2011] [Accepted: 07/08/2011] [Indexed: 01/17/2023]
Abstract
Gastrointestinal (GI) motility and gut hormones have been considered to be involved in the development and maintenance of obesity. Our aim was to assess the relationships between gastric emptying (GE), GI transit and gut hormones and leptin concentrations in diet-induced obese rat model. Male 6-week-old Sprague-Dawley rats were fed with a high-fat (HF) diet for 8weeks to generate diet-induced obesity (DIO) and diet resistant (DR) rats. GE, GI transit and plasma ghrelin, cholecystokinin (CCK), PYY and leptin concentrations were determined in DIO, DR and control (CON) rats. The DIO rats had slower GE, higher plasma leptin and CCK concentrations, and lower plasma ghrelin concentration compared with CON and DR rats. GE was correlated with plasma ghrelin (r=0.402, P=0.028), CCK (r=-0.518, P=0.003) and leptin concentration (r=-0.514, P=0.004). The slower GE, which can be considered as an adaptive response aimed at HF diet induced obesity, may be mediated by changes of plasma ghrelin, CCK and leptin concentrations.
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Affiliation(s)
- Jie Li
- Department of Nutrition and Food Hygiene, School of Public Health, Harbin Medical University, Harbin, PR China
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Abstract
The intestine is an important metabolic organ that has gained attention in recent years for the newly identified role that it plays in the pathophysiology of various metabolic diseases including obesity, insulin resistance and diabetes. Recent insights regarding the role of enteroendocrine hormones, such as GIP, GLP-1, and PYY in metabolic diseases, as well as the emerging role of the gut microbial community and gastric bypass bariatric surgeries in modulating metabolic function and dysfunction have sparked a wave of interest in understanding the mechanisms involved, in an effort to identify new therapeutics and novel regulators of metabolism. This review summarizes the current evidence that the gastrointestinal tract has a key role in the development of obesity, inflammation, insulin resistance and diabetes and discusses the possible players that can be targeted for therapeutic intervention.
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Affiliation(s)
- William D Bradley
- Metabolic and Vascular Diseases Department, Hoffmann La-Roche Inc., Nutley, NJ, USA
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30
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Hedberg J, Hedenström H, Karlsson FA, Edén-Engström B, Sundbom M. Gastric Emptying and Postprandial PYY Response After Biliopancreatic Diversion with Duodenal Switch. Obes Surg 2010; 21:609-15. [DOI: 10.1007/s11695-010-0288-7] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
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Delzenne N, Blundell J, Brouns F, Cunningham K, De Graaf K, Erkner A, Lluch A, Mars M, Peters HPF, Westerterp-Plantenga M. Gastrointestinal targets of appetite regulation in humans. Obes Rev 2010; 11:234-50. [PMID: 20433660 DOI: 10.1111/j.1467-789x.2009.00707.x] [Citation(s) in RCA: 107] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The aim of this paper is to describe and discuss relevant aspects of the assessment of physiological functions - and related biomarkers - implicated in the regulation of appetite in humans. A short introduction provides the background and the present state of biomarker research as related to satiety and appetite. The main focus of the paper is on the gastrointestinal tract and its functions and biomarkers related to appetite for which sufficient data are available in human studies. The first section describes how gastric emptying, stomach distension and gut motility influence appetite; the second part describes how selected gastrointestinal peptides are involved in the control of satiety and appetite (ghrelin, cholecystokinin, glucagon-like peptide, peptide tyrosin-tyrosin) and can be used as potential biomarkers. For both sections, methodological aspects (adequacy, accuracy and limitation of the methods) are described. The last section focuses on new developments in techniques and methods for the assessment of physiological targets involved in appetite regulation (including brain imaging, interesting new experimental approaches, targets and markers). The conclusion estimates the relevance of selected biomarkers as representative markers of appetite regulation, in view of the current state of the art.
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Affiliation(s)
- N Delzenne
- Louvain Drug Research Institute, Unit PMNT 7369, Université Catholique de Louvain, Brussels, Belgium
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Witte AB, Grybäck P, Holst J, Hilsted L, Hellström P, Jacobsson H, Schmidt P. Differential effect of PYY1-36 and PYY3-36 on gastric emptying in man. ACTA ACUST UNITED AC 2009; 158:57-62. [DOI: 10.1016/j.regpep.2009.07.013] [Citation(s) in RCA: 49] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2009] [Revised: 06/03/2009] [Accepted: 07/23/2009] [Indexed: 01/11/2023]
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Sir David Cuthbertson Medal Lecture Bariatric surgery as a model to study appetite control. Proc Nutr Soc 2009; 68:227-33. [DOI: 10.1017/s0029665109001256] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
The obesity epidemic and its associated morbidity and mortality have led to major research efforts to identify mechanisms that regulate appetite. Gut hormones have recently been found to be an important element in appetite regulation as a result of the signals from the periphery to the brain. Candidate hormones include ghrelin, peptide YY, glucagon-like peptide-1 and gastric inhibitory polypeptide, all of which are currently being investigated as potential obesity treatments. Bariatric surgery is currently the most effective therapy for substantial and sustained weight loss. Understanding how levels of gut hormones are modulated by such procedures has greatly contributed to the comprehension of the underlying mechanisms of appetite and obesity. The present paper is a review of how appetite and levels of gastrointestinal hormones are altered after bariatric surgery. Basic principles of common bariatric procedures and potential mechanisms for appetite regulation by gut hormones are also addressed.
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Khoo J, Rayner CK, Jones KL, Horowitz M. Pathophysiology and management of gastroparesis. Expert Rev Gastroenterol Hepatol 2009; 3:167-181. [PMID: 19351287 DOI: 10.1586/egh.09.10] [Citation(s) in RCA: 20] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Gastroparesis is characterized by upper gastrointestinal symptoms associated with delayed gastric emptying, without mechanical obstruction. However, symptoms do not correlate well with the magnitude of delay in gastric emptying. Diabetes mellitus and surgery are the most common causes, although more than 30% of cases are idiopathic. Coordination of insulin action with nutrient delivery is important in diabetics, as postprandial blood glucose levels and gastric emptying are interdependent, and gastroparesis probably represents a major cause of poor glycemic control. Scintigraphy is the gold standard for measuring gastric emptying. Current treatment mainly involves the use of prokinetic drugs. Pyloric botulinum toxin injection and gastric electrical stimulation require more evidence from controlled studies before their use can be recommended. Surgical options remain inadequately studied.
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Affiliation(s)
- Joan Khoo
- Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, South Australia, Australia
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Hall J, Roberts R, Vora N. Energy homoeostasis: The roles of adipose tissue-derived hormones, peptide YY and Ghrelin. Obes Facts 2009; 2:117-25. [PMID: 20054215 PMCID: PMC6444707 DOI: 10.1159/000208517] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/17/2022] Open
Abstract
This review discusses the physiology of the hormones leptin, adiponectin, resistin, peptide YY, and ghrelin and how each of these contributes to energy homoeostasis, weight regulation, and the pathogenesis of obesity. The relationship these hormones have with insulin and insulin resistance is also discussed, and the potential therapeutic use of each of these hormones is also considered.
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Abstract
The obesity epidemic is a major health problem that is associated with increased morbidity and mortality. Gastrointestinal hormones have been increasingly understood to be an important element in appetite regulation. Several gastrointestinal hormones can contribute to obesity by modulating the activity of the gut-brain axis. Bariatric surgery is currently the most effective therapy for significant and sustained weight loss in morbidly obese patients. Understanding how gut hormones are altered by bariatric procedures has contributed to our understanding of the mechanisms of appetite. In this review, we address several gastrointestinal hormones that are associated with obesity and consider how their levels are altered after bariatric surgery. The review also addresses specific effects of different gut hormones on appetite, hunger, and energy balance.
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Affiliation(s)
| | | | - Carel W. le Roux
- *Dr. Carel W. le Roux, MBChB, Ph.D., MRCP, MRCPath Department of Investigative Medicine Hammersmith Hospital, Imperial College London Du Cane Road, London, W12 0NN, UK Tel. +44 20 83833242
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No evidence of an additive inhibitory feeding effect following PP and PYY 3-36 administration. Int J Obes (Lond) 2008; 32:1438-40. [PMID: 18607381 DOI: 10.1038/ijo.2008.95] [Citation(s) in RCA: 27] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Pancreatic polypeptide (PP) and peptide YY (PYY) are released by the gut in response to nutrients and inhibit food intake in rodents and humans. We hypothesized that PP and PYY(3-36) would inhibit feeding additively. Fasted male C57BL/6 mice were injected intraperitoneally with saline, PP, PYY(3-36) or PP+PYY(3-36) (n=7-10). Food intake at 1 h was significantly inhibited by 6 nmol kg(-1) PP and by 6 nmol kg(-1) PYY(3-36) (P<0.05) but not significantly following 3 nmol kg(-1) PP+3 nmol kg(-1) PYY(3-36). In a higher dose study 30 nmol kg(-1) PP, 30 nmol kg(-1) PYY(3-36) and 30 nmol kg(-1) PP+30 nmol kg(-1) PYY(3-36) all inhibited 1 h food intake compared with saline (P<0.05) but there was no significant difference in the food intake of the combined group compared with either hormone individually. Subsequently, 16 fasted lean healthy human volunteers (6 men and 10 women) received, in random order, 90 min intravenous infusions of saline, 4 pmol kg(-1)min(-1) PP, 0.4 pmol kg(-1)min(-1) PYY(3-36) and 4 pmol kg(-1)min(-1) PP+0.4 pmol kg(-1)min(-1) PYY(3-36). A pasta lunch was served 60 min following infusion. There was no evidence of a greater decrease in food intake with the combined PP+PYY(3-36) treatment (buffet meal energy intake (KJ): saline 2633+/-204, PP+PYY 2693+/-254, PP 2367+/-199, PYY 2511+/-196). These results suggest that PP and PYY(3-36) do not inhibit feeding additively in rodents or humans.
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Vincent RP, Ashrafian H, le Roux CW. Mechanisms of disease: the role of gastrointestinal hormones in appetite and obesity. ACTA ACUST UNITED AC 2008; 5:268-77. [PMID: 18382432 DOI: 10.1038/ncpgasthep1118] [Citation(s) in RCA: 50] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2007] [Accepted: 02/11/2008] [Indexed: 12/25/2022]
Abstract
The obesity epidemic is fast becoming one of the leading causes of mortality and morbidity worldwide. Over the past 30 years, gastrointestinal hormones have been increasingly understood to have an important role as regulators of appetite and energy balance in obese individuals. The levels of these hormones are modulated by bariatric surgery, and understanding how they are affected by such procedures can contribute to our comprehension of the underlying mechanisms by which these hormones affect obesity and its treatment. In this Review, we consider several gastrointestinal hormones that can contribute to obesity by modulating the activity of the gut-brain axis, and examine their specific effects on appetite, hunger and energy balance. Better understanding of the mechanisms by which these peptides exert their effects may enable the development of improved weight-loss medications and new treatments for obesity.
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Affiliation(s)
- Royce P Vincent
- Department of Chemical Pathology, King's College Hospital NHS Foundation Trust, London, UK
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Borg CM, le Roux CW, Ghatei MA, Bloom SR, Patel AG. Biliopancreatic diversion in rats is associated with intestinal hypertrophy and with increased GLP-1, GLP-2 and PYY levels. Obes Surg 2008; 17:1193-8. [PMID: 18074494 DOI: 10.1007/s11695-007-9211-2] [Citation(s) in RCA: 44] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
BACKGROUND Factors leading to weight loss and weight stabilization after bariatric surgery are not fully understood. The aims of this study were to develop an animal model for biliopancreatic diversion (BPD) and to determine changes in gut hormones, malabsorption and small bowel histology postoperatively. METHODS 2 groups of Wistar rats underwent sham and BPD surgery. Daily postoperative weights and food intake were measured. 24-hour fecal collections were performed at Day 6 and 21. Bomb calorimetry was performed to determine the fecal calorific values. At day 23, levels of peptide YY (PYY), glucagon-like peptide 1 (GLP-1) and glucagon-like peptide 2 (GLP-2) were determined and small bowel biopsies were taken. RESULTS Animals in the BPD group had significant reduction in weight (P<0.001) and in food intake (P<0.001) compared to the sham group. Serum levels of PYY, GLP-1 and GLP-2 in the BPD group were significantly higher (P<0.005). Animals in the BPD group had significantly higher fecal energy content at Day 6 (P<0.001) but not at Day 21 when compared to the sham group. Small bowel histology confirmed the presence of significantly increased mitosis (P=0.03) and labelled cells (P=0.002) in the BPD animals when compared to sham. CONCLUSIONS In our animal model, the higher levels of PYY, GLP-1 and GLP-2 after BPD may be due to gut adaptation and hypertrophy and could be important in inducing and maintaining weight loss after bariatric surgery.
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Affiliation(s)
- Cynthia M Borg
- Department of Surgery, King's College Hospital, London, UK.
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Takeda Y, Koh SD, Sanders KM, Ward SM. Differential expression of ionic conductances in interstitial cells of Cajal in the murine gastric antrum. J Physiol 2007; 586:859-73. [PMID: 18033817 DOI: 10.1113/jphysiol.2007.140293] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
Two distinct populations of interstitial cells of Cajal (ICC) exist within the tunica muscularis of the gastric antrum, and these cells serve different physiological functions. One population of ICC generates and actively propagates electrical slow waves, and the other population of ICC is innervated by excitatory and inhibitory motor neurons and mediates enteric motor neurotransmission. In spite of the key role of ICC in gastric excitability, little is known about the ionic conductances that underlie the functional diversity of these cells. In the present study we isolated ICC from the murine gastric antrum and investigated the Ca(2+)-dependent ionic conductances expressed by these cells using the patch clamp technique. Conductances in ICC were compared with those expressed in smooth muscle cells. The cells studied were identified by RT-PCR using cell-specific primers that included Myh11 (smooth muscle cells), Kit (ICC) and Uchl1 (enteric neurons) following electrophysiolgical recordings. Distinct ionic conductances were observed in Kit-positive cells. One group of ICC expressed a basal non-selective cation conductance (NSCC) that was inhibited by an increase in [Ca(2+)](i) in a calmodulin (CaM)-dependent manner. A second population of ICC generated spontaneous transient inward currents (STICs) and expressed a basal noisy NSCC that was facilitated by an increase in [Ca(2+)](i) in a CaM-dependent manner. The [Ca(2+)](i)-facilitated NSCC in ICC was blocked by the Cl(-) channel antagonists 4,4'-diisothiocyanatostilbene-2,2'-disulphonic acid (DIDS), anthracene-9-carboxylate (9-AC) and niflumic acid. These data suggest that distinct NSCC are expressed in subpopulations of ICC and these conductances may underlie the functional differences of these cells within the gastric antrum.
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Affiliation(s)
- Yukari Takeda
- Department of Physiology and Cell Biology, University of Nevada School of Medicine, Reno, NV 89557, USA
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42
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Wynne K, Bloom SR. The role of oxyntomodulin and peptide tyrosine-tyrosine (PYY) in appetite control. ACTA ACUST UNITED AC 2007; 2:612-20. [PMID: 17082808 DOI: 10.1038/ncpendmet0318] [Citation(s) in RCA: 53] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2006] [Accepted: 06/12/2006] [Indexed: 01/10/2023]
Abstract
Oxyntomodulin and peptide tyrosine-tyrosine (PYY) are released from intestinal enteroendocrine cells in response to a meal. These circulating hormones are considered to be satiety signals, as they have been found to decrease food intake, body weight and adiposity in rodents. Their effect on energy homeostasis is mediated by the hypothalamus and brainstem, and several studies have demonstrated alterations in neuropeptide signaling within the arcuate nucleus. The weight loss that has been observed in animal models after repeated administration of oxyntomodulin and PYY has led to interest in developing these peptides as antiobesity therapies in humans. Indeed, preliminary studies have found that oxyntomodulin or PYY administration reduces food intake and body weight effectively in overweight human volunteers. This research suggests that modulation of these gut hormones could prove to be effective long-term therapies in the quest to combat the obesity epidemic.
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Affiliation(s)
- Katie Wynne
- Department of Metabolic Medicine, Imperial College London, and Hammersmith Hospital, UK
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43
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Bloomgarden ZT. Gut hormones, obesity, polycystic ovarian syndrome, malignancy, and lipodystrophy syndromes. Diabetes Care 2007; 30:1934-9. [PMID: 17596508 DOI: 10.2337/dc07-zb07] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
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Nguyen NQ, Fraser RJ, Bryant LK, Chapman MJ, Wishart J, Holloway RH, Butler R, Horowitz M. The relationship between gastric emptying, plasma cholecystokinin, and peptide YY in critically ill patients. Crit Care 2007; 11:R132. [PMID: 18154642 PMCID: PMC2246231 DOI: 10.1186/cc6205] [Citation(s) in RCA: 37] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2007] [Revised: 11/23/2007] [Accepted: 12/21/2007] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Cholecystokinin (CCK) and peptide YY (PYY) are released in response to intestinal nutrients and play an important physiological role in regulation of gastric emptying (GE). Plasma CCK and PYY concentrations are elevated in critically ill patients, particularly in those with a history of feed intolerance. This study aimed to evaluate the relationship between CCK and PYY concentrations and GE in critical illness. METHODS GE of 100 mL of Ensure meal (106 kcal, 21% fat) was measured using a 13C-octanoate breath test in 39 mechanically ventilated, critically ill patients (24 males; 55.8 +/- 2.7 years old). Breath samples for 13CO2 levels were collected over the course of 4 hours, and the GE coefficient (GEC) (normal = 3.2 to 3.8) was calculated. Measurements of plasma CCK, PYY, and glucose concentrations were obtained immediately before and at 60 and 120 minutes after administration of Ensure. RESULTS GE was delayed in 64% (25/39) of the patients. Baseline plasma CCK (8.5 +/- 1.0 versus 6.1 +/- 0.4 pmol/L; P = 0.045) and PYY (22.8 +/- 2.2 versus 15.6 +/- 1.3 pmol/L; P = 0.03) concentrations were higher in patients with delayed GE and were inversely correlated with GEC (CCK: r = -0.33, P = 0.04, and PYY: r = -0.36, P = 0.02). After gastric Ensure, while both plasma CCK (P = 0.03) and PYY (P = 0.02) concentrations were higher in patients with delayed GE, there was a direct relationship between the rise in plasma CCK (r = 0.40, P = 0.01) and PYY (r = 0.42, P < 0.01) from baseline at 60 minutes after the meal and the GEC. CONCLUSION In critical illness, there is a complex interaction between plasma CCK, PYY, and GE. Whilst plasma CCK and PYY correlated moderately with impaired GE, the pathogenetic role of these gut hormones in delayed GE requires further evaluation with specific antagonists.
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Affiliation(s)
- Nam Q Nguyen
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000
- Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, 5000
| | - Robert J Fraser
- Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, 5000
- Investigation and Procedures Unit, Repatriation General Hospital, Daw Road, Adelaide, South Australia, 5000
| | - Laura K Bryant
- Investigation and Procedures Unit, Repatriation General Hospital, Daw Road, Adelaide, South Australia, 5000
| | - Marianne J Chapman
- Department of Anaesthesia and Intensive Care, Royal Adelaide Hospital, Adelaide, South Australia, 5000
| | - Judith Wishart
- Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, 5000
| | - Richard H Holloway
- Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, North Terrace, Adelaide, South Australia, 5000
- Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, 5000
| | - Ross Butler
- Centre for Paediatric and Adolescent Gastroenterology, Children, Youth and Women's Health Service, Adelaide, South Australia, 5000
| | - Michael Horowitz
- Discipline of Medicine, University of Adelaide, Royal Adelaide Hospital, Adelaide, South Australia, 5000
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Abstract
Gut hormones signal to the central nervous system to influence energy homeostasis. Evidence supports the existence of a system in the gut that senses the presence of food in the gastrointestinal tract and signals to the brain via neural and endocrine mechanisms to regulate short-term appetite and satiety. Recent evidence has shown that specific gut hormones administered at physiological or pathophysiological concentrations can influence appetite in rodents and humans. Gut hormones therefore have an important physiological role in postprandial satiety, and gut hormone signaling systems represent important pharmaceutical targets for potential antiobesity therapies. Our laboratory investigates the role of gut hormones in energy homeostasis and has a particular interest in this field of translational research. In this review we describe our initial studies and the results of more recent investigations into the effects of the gastric hormone ghrelin and the intestinal hormones peptide YY, pancreatic polypeptide, glucagon-like peptide-1, and oxyntomodulin on energy homeostasis. We also speculate on the role of gut hormones in the future treatment of obesity.
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Affiliation(s)
- Kevin G Murphy
- Department of Metabolic Medicine, Imperial College Faculty of Medicine, Hammersmith Campus, London W12 ONN, UK
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Levin F, Edholm T, Schmidt PT, Grybäck P, Jacobsson H, Degerblad M, Höybye C, Holst JJ, Rehfeld JF, Hellström PM, Näslund E. Ghrelin stimulates gastric emptying and hunger in normal-weight humans. J Clin Endocrinol Metab 2006; 91:3296-302. [PMID: 16772353 DOI: 10.1210/jc.2005-2638] [Citation(s) in RCA: 223] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
CONTEXT Ghrelin is produced primarily by enteroendocrine cells in the gastric mucosa and increases gastric emptying in patients with gastroparesis. MAIN OBJECTIVE The objective of the study was to evaluate the effect of ghrelin on gastric emptying, appetite, and postprandial hormone secretion in normal volunteers. DESIGN This was a randomized, double-blind, crossover study. SUBJECTS Subjects included normal human volunteers and patients with GH deficiency. INTERVENTION Intervention included saline or ghrelin (10 pmol/kg.min) infusion for 180 min after intake of a radioactively labeled omelette (310 kcal) or GH substitution in GH-deficient patients. MAIN OUTCOME MEASURES Measures consisted of gastric empty-ing parameters and postprandial plasma levels of ghrelin, cholecystokinin, glucagon-like peptide-1, peptide YY, and motilin. RESULTS The emptying rate was significantly faster for ghrelin (1.26 +/- 0.1% per minute), compared with saline (0.83% per minute) (P < 0.001). The lag phase (16.2 +/- 2.2 and 26.5 +/- 3.8 min) and half-emptying time (49.4 +/- 3.9 and 75.6 +/- 4.9 min) of solid gastric emptying were shorter during ghrelin infusion, compared with infusion of saline (P < 0.001). The postprandial peak in plasma concentration for cholecystokinin and glucagon-like peptide-1 occurred earlier and was higher during ghrelin infusion. There was no significant effect of ghrelin on plasma motilin or peptide YY. There was no difference in gastric emptying before and after GH substitution. CONCLUSION Our results demonstrate that ghrelin increases the gastric emptying rate in normal humans. The effect does not seem to be mediated via GH or motilin but may be mediated by the vagal nerve or directly on ghrelin receptors in the stomach. Ghrelin receptor agonists may have a role as prokinetic agents.
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Affiliation(s)
- F Levin
- Department of Surgery, Danderyd Hospital, SE-182 88 Stockholm, Sweden.
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Camilleri M. Integrated upper gastrointestinal response to food intake. Gastroenterology 2006; 131:640-58. [PMID: 16890616 DOI: 10.1053/j.gastro.2006.03.023] [Citation(s) in RCA: 153] [Impact Index Per Article: 8.1] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/04/2006] [Accepted: 03/16/2006] [Indexed: 12/14/2022]
Affiliation(s)
- Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.) Group, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
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Abstract
The role of gastrointestinal hormones in the regulation of appetite is reviewed. The gastrointestinal tract is the largest endocrine organ in the body. Gut hormones function to optimize the process of digestion and absorption of nutrients by the gut. In this capacity, their local effects on gastrointestinal motility and secretion have been well characterized. By altering the rate at which nutrients are delivered to compartments of the alimentary canal, the control of food intake arguably constitutes another point at which intervention may promote efficient digestion and nutrient uptake. In recent decades, gut hormones have come to occupy a central place in the complex neuroendocrine interactions that underlie the regulation of energy balance. Many gut peptides have been shown to influence energy intake. The most well studied in this regard are cholecystokinin (CCK), pancreatic polypeptide, peptide YY, glucagon-like peptide-1 (GLP-1), oxyntomodulin and ghrelin. With the exception of ghrelin, these hormones act to increase satiety and decrease food intake. The mechanisms by which gut hormones modify feeding are the subject of ongoing investigation. Local effects such as the inhibition of gastric emptying might contribute to the decrease in energy intake. Activation of mechanoreceptors as a result of gastric distension may inhibit further food intake via neural reflex arcs. Circulating gut hormones have also been shown to act directly on neurons in hypothalamic and brainstem centres of appetite control. The median eminence and area postrema are characterized by a deficiency of the blood-brain barrier. Some investigators argue that this renders neighbouring structures, such as the arcuate nucleus of the hypothalamus and the nucleus of the tractus solitarius in the brainstem, susceptible to influence by circulating factors. Extensive reciprocal connections exist between these areas and the hypothalamic paraventricular nucleus and other energy-regulating centres of the central nervous system. In this way, hormonal signals from the gut may be translated into the subjective sensation of satiety. Moreover, the importance of the brain-gut axis in the control of food intake is reflected in the dual role exhibited by many gut peptides as both hormones and neurotransmitters. Peptides such as CCK and GLP-1 are expressed in neurons projecting both into and out of areas of the central nervous system critical to energy balance. The global increase in the incidence of obesity and the associated burden of morbidity has imparted greater urgency to understanding the processes of appetite control. Appetite regulation offers an integrated model of a brain-gut axis comprising both endocrine and neurological systems. As physiological mediators of satiety, gut hormones offer an attractive therapeutic target in the treatment of obesity.
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Affiliation(s)
| | | | - Steve Bloom
- Department of Metabolic Medicine, Imperial College Faculty of MedicineHammersmith Hospital, Du Cane Road, London W12 ONN, UK
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Martin GR, Beck PL, Sigalet DL. Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation. World J Gastroenterol 2006; 12:4117-29. [PMID: 16830359 PMCID: PMC4087358 DOI: 10.3748/wjg.v12.i26.4117] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable.
Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.
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Affiliation(s)
- G-R Martin
- Department of Gastrointestinal Sciences, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW., Calgary, Alberta T2N 4N1, Canada.
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Urita Y, Sugimoto M, Hike K, Torii N, Kikuchi Y, Kurakata H, Kanda E, Sasajima M, Miki K. High incidence of fermentation in the digestive tract in patients with reflux oesophagitis. Eur J Gastroenterol Hepatol 2006; 18:531-5. [PMID: 16607150 DOI: 10.1097/00042737-200605000-00013] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
OBJECTIVES Because bacteria represent the sole source of gut hydrogen (H2) and methane (CH4), fasting breath H2 and CH4 gases have been used as markers of colonic fermentation. The presence of carbohydrates in the colonic lumen inhibits gastric and pancreatic secretions, and also influences lower oesophageal sphincter function in gastro-oesophageal reflux disease. MATERIALS AND METHODS Studies were performed in 793 consecutive patients undergoing oesophagogastroscopy (270 men and 523 women, aged 19-85 years). A fasting breath sample (20 ml) was collected before endoscopy. At endoscopy, we intubated the stomach without inflation by air, and 20 ml of intragastric gas was collected through the biopsy channel. Next, the tip of the endoscope was inserted into the second portion of the duodenum without inflation by air, and 20 ml of intraduodenal gas was collected. H2 and CH4 concentrations of each sample were measured by gas chromatography. RESULTS Reflux oesophagitis was found in 147 of the 793 patients. The mean values of the H2 and/or CH4 levels of samples taken from the stomach, duodenum and exhaled air were higher in patients with reflux oesophagitis than those without reflux oesophagitis. High H2 and/or CH4 levels were more frequently found in patients with reflux oesophagitis. CONCLUSIONS We concluded that the presence of fermentation in the digestive tract was considered to be a risk factor for developing reflux oesophagitis.
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Affiliation(s)
- Yoshihisa Urita
- Department of General Medicine and Emergency Care, Toho University School of Medicine, Omori Hospital, 6-11-1 Omori-Nishi, Ota-Ku, Tokyo 143-8541, Japan.
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