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Wilbrink JA, van Avesaat M, Nienhuijs SW, Stronkhorst A, Masclee AAM. Changes in gastrointestinal motility and gut hormone secretion after Roux-en-Y gastric bypass and sleeve gastrectomy for individuals with severe obesity. Clin Obes 2025; 15:e12721. [PMID: 39727180 PMCID: PMC11907097 DOI: 10.1111/cob.12721] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/09/2023] [Accepted: 10/23/2024] [Indexed: 12/28/2024]
Abstract
BACKGROUND Bariatric surgery is very effective in long-term weight management. The present study was undertaken to investigate the short-term effects of sleeve gastrectomy (SG) and of Roux-en-Y gastric bypass (RYGB) on (a) gastrointestinal (GI) motility, that is gastric emptying and oro-cecal transit time and (b) secretion of regulatory gut peptides and (c) their interrelationship. METHODS Prospective single-centre study in which we assessed gastric emptying, oro-cecal transit time and gut peptide release in 28 severely obese individuals before and 2, respectively, 12 months after bariatric surgery (either SG or RYGB). Plasma PYY, GLP-1, ghrelin, insulin and glucose levels were measured fasting and after intake of a solid standard 459 kcal meal at each occasion. Gastric emptying was measured by 13 C octanoic acid breath testing, and oro-cecal transit time was measured by lactulose H2 breath testing. Satiation was measured using VAS scores. RESULTS After both RYGB and SG gastric emptying become significantly accelerated, and postprandial release of the distal gut peptides GLP-1 and PYY becomes significantly increased, pointing to ileal brake activation. Oro-cecal transit time becomes significantly accelerated after SG but not after RYGB. No significant correlations were observed between changes in distal gut peptide release, changes in GI motility and clinical parameters. CONCLUSION Both SG and RYGB resulted in significant weight loss and significantly affected GI motility and PYY and GLP-1 secretion. Subtle differences between both procedures were found in effect on oro-cecal transit time and patterns of peptide secretion.
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Affiliation(s)
- Jennifer A. Wilbrink
- Division of Gastroenterology‐HepatologyMaastricht University Medical Center, Maastricht, The Netherlands. NUTRIM—School for Nutrition and Translational Research in MetabolismMaastrichtthe Netherlands
- Department of Gastroenterology‐HepatologyCatharina HospitalEindhoventhe Netherlands
- Department of Gastroenterology‐HepatologyZuyderland Medical Centre Sittard‐GeleenBG Geleenthe Netherlands
| | - Mark van Avesaat
- Division of Gastroenterology‐HepatologyMaastricht University Medical Center, Maastricht, The Netherlands. NUTRIM—School for Nutrition and Translational Research in MetabolismMaastrichtthe Netherlands
- Department of Gastroenterology‐HepatologyZuyderland Medical Centre Sittard‐GeleenBG Geleenthe Netherlands
| | | | - Arnold Stronkhorst
- Department of Gastroenterology‐HepatologyCatharina HospitalEindhoventhe Netherlands
| | - Ad A. M. Masclee
- Division of Gastroenterology‐HepatologyMaastricht University Medical Center, Maastricht, The Netherlands. NUTRIM—School for Nutrition and Translational Research in MetabolismMaastrichtthe Netherlands
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Chapela S, Alvarez-Córdova L, Martinuzzi A, Suarez R, Gonzalez V, Manrique E, Castaño J, Rossetti G, Cobellis L, Pilone V, Frias-Toral E, Schiavo L. Neurobiological and Microbiota Alterations After Bariatric Surgery: Implications for Hunger, Appetite, Taste, and Long-Term Metabolic Health. Brain Sci 2025; 15:363. [PMID: 40309850 PMCID: PMC12025976 DOI: 10.3390/brainsci15040363] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2025] [Revised: 03/27/2025] [Accepted: 03/28/2025] [Indexed: 05/02/2025] Open
Abstract
Bariatric surgery (BS) is an effective intervention for obesity, inducing significant neurobiological and gut microbiota changes that influence hunger, appetite, taste perception, and long-term metabolic health. This narrative review examines these alterations by analyzing recent findings from clinical and preclinical studies, including neuroimaging, microbiome sequencing, and hormonal assessments. BS modulates appetite-regulating hormones, reducing ghrelin while increasing glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY), leading to enhanced satiety and decreased caloric intake. Neuroimaging studies reveal structural and functional changes in brain regions involved in reward processing and cognitive control, contributing to reduced cravings and altered food choices. Additionally, BS reshapes the gut microbiota, increasing beneficial species such as Akkermansia muciniphila, which influence metabolic pathways through short-chain fatty acid production and bile acid metabolism. These findings highlight the complex interplay between the gut and the brain in post-surgical metabolic regulation. Understanding these mechanisms is essential for optimizing post-operative care, including nutritional strategies and behavioral interventions. Future research should explore how these changes impact long-term outcomes, guiding the development of targeted therapies to enhance the recovery and quality of life for BS patients.
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Affiliation(s)
- Sebastián Chapela
- Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Ciudad Autónoma de Buenos Aires C1121ABG, Argentina;
- Unidad de Soporte Nutricional, Hospital Británico de Buenos Aires, Ciudad Autónoma de Buenos Aires C1280AEB, Argentina
| | - Ludwig Alvarez-Córdova
- Facultad de Ciencias de la Salud, Universidad de las Américas (UDLA), Quito 170513, Ecuador
| | - Andres Martinuzzi
- Unidad de Soporte Nutricional, Sanatorio Rio Negro, Rio Negro R8500BAD, Argentina;
- Asuntos Profesionales y Educación, Fresenius Kabi Argentina, Ciudad de Buenos Aires C1428AAU, Argentina
| | - Rosario Suarez
- School of Medicine, Universidad Técnica Particular de Loja, Calle París, San Cayetano Alto, Loja 110107, Ecuador;
| | - Victoria Gonzalez
- Unidad de Soporte Metabólico y Nutricional, Sanatorio Allende, Córdoba X5000BFB, Argentina;
- Facultad de Ciencias de la Salud, Universidad Católica de Córdoba, Córdoba X5000IYG, Argentina
| | - Ezequiel Manrique
- Unidad de Soporte Nutricional, Hospital Privado Universitario de Córdoba, Córdoba X5016KEH, Argentina;
| | - Janeth Castaño
- Pediatrics, Family Medicine Department, Indiana University Health, Lafayette, IN 47905, USA;
| | - Gianluca Rossetti
- General and Bariatric Surgery Unit, Abano Terme Policlinic, 35031 Padova, Italy;
| | - Luigi Cobellis
- Unit of General Surgery, Casa Di Cura “Prof. Dott. Luigi Cobellis”, 84078 Vallo Della Lucania, Italy;
| | - Vincenzo Pilone
- Public Health Department, Naples “Federico II” University, AOU “Federico II”, Via S. Pansini 5, 80131 Naples, Italy;
| | - Evelyn Frias-Toral
- Escuela de Medicina, Universidad Espíritu Santo, Samborondón 0901952, Ecuador;
- Division of Research, Texas State University, 601 University Dr, San Marcos, TX 78666, USA
| | - Luigi Schiavo
- Department of Medicine, Surgery and Dentistry “Scuola Medica Salernitana”, University of Salerno, 84081 Baronissi, Italy
- NBFC—National Biodiversity Future Center, 90133 Palermo, Italy
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Ferraz ÁAB, Vianna CFM, Henriques DF, Gorgulho GCF, Santa-Cruz F, Siqueira LT, Kreimer F. The Impact of Cholecystectomy on the Metabolic Profile of Patients Previously Submitted to Bariatric Surgery. Surg Laparosc Endosc Percutan Tech 2025; 35:e1348. [PMID: 39618187 DOI: 10.1097/sle.0000000000001348] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2024] [Accepted: 11/05/2024] [Indexed: 01/04/2025]
Abstract
PURPOSE To evaluate the influence of late cholecystectomy following bariatric surgery on the postoperative evolution of weight loss and biochemical, metabolic, and micronutrient parameters. METHODS A retrospective study that assessed 86 patients who underwent cholecystectomy after at least 18 months of bariatric surgery. The analyzed variables included demographic data, comorbidities, weight loss, and biochemical, metabolic, and micronutrient parameters. RESULTS Among the analyzed patients, 20 underwent gastric bypass (GB) and 66 underwent sleeve gastrectomy (SG). The GB group comprised 55% of women, with a mean age of 54.4 years and a mean preoperative body mass index (BMI) of 29.2 kg/m 2 . The mean time elapsed between GB and cholecystectomy was 118.3±43.9 months. The sample of SG comprised 83.3% of women, with a mean age of 41.1 years and a mean preoperative BMI of 28.7 kg/m 2 . The mean time elapsed between SG and cholecystectomy was 26.1±17.5 months. Both SG and GB groups showed a reduction in the mean BMI, but it was not statistically significant after cholecystectomy. In the metabolic, biochemical, and micronutrient evaluation, there was no statistically significant difference, except in the GB group, where an increase in vitamin D was observed after cholecystectomy with statistical significance. CONCLUSION Cholecystectomy does not negatively impact the clinical and anthropometric evolution of patients previously submitted to bariatric surgery.
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Affiliation(s)
| | - Cassio F M Vianna
- Medical School, Federal University of Pernambuco, Recife, PE, Brazil
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Hussan H, Ali MR, Lyo V, Webb A, Pietrzak M, Zhu J, Choueiry F, Li H, Cummings BP, Marco ML, Medici V, Clinton SK. Bariatric Surgery Is Associated with Lower Concentrations of Fecal Secondary Bile Acids and Their Metabolizing Microbial Enzymes: A Pilot Study. Obes Surg 2024; 34:3420-3433. [PMID: 39042309 DOI: 10.1007/s11695-024-07420-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 07/04/2024] [Accepted: 07/17/2024] [Indexed: 07/24/2024]
Abstract
INTRODUCTION Excess body fat elevates colorectal cancer risk. While bariatric surgery (BRS) induces significant weight loss, its effects on the fecal stream and colon biology are poorly understood. Specifically, limited data exist on the impact of bariatric surgery (BRS) on fecal secondary bile acids (BA), including lithocholic acid (LCA), a putative promotor of colorectal carcinogenesis. METHODS This cross-sectional case-control study included 44 patients with obesity; 15 pre-BRS (controls) vs. 29 at a median of 24.1 months post-BRS. We examined the fecal concentrations of 11 BA by liquid chromatography and gene abundance of BA-metabolizing bacterial enzymes through fecal metagenomic sequencing. Differences were quantified using non-parametric tests for BA levels and linear discriminant analysis (LDA) effect size (LEfSe) for genes encoding BA-metabolizing enzymes. RESULTS Total fecal secondary BA concentrations trended towards lower levels post- vs. pre-BRS controls (p = 0.07). Individually, fecal LCA concentrations were significantly lower post- vs. pre-BRS (8477.0 vs. 11,914.0 uM/mg, p < 0.008). Consistent with this finding, fecal bacterial genes encoding BA-metabolizing enzymes, specifically 3-betahydroxycholanate-3-dehydrogenase (EC 1.1.1.391) and 3-alpha-hydroxycholanate dehydrogenase (EC 1.1.1.52), were also lower post- vs. pre-BRS controls (LDA of - 3.32 and - 2.64, respectively, adjusted p < 0.0001). Post-BRS fecal BA concentrations showed significant inverse correlations with weight loss, a healthy diet quality, and increased physical activity. CONCLUSIONS Concentrations of LCA, a secondary BA, and bacterial genes needed for BA metabolism are lower post-BRS. These changes can impact health and modulate the colorectal cancer cascade. Further research is warranted to examine how surgical alterations and the associated dietary changes impact bile acid metabolism.
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Affiliation(s)
- Hisham Hussan
- Division of Gastroenterology, Department of Internal Medicine, University of California, Davis, Sacramento, CA, 95616, USA.
- The UC Davis Comprehensive Cancer Center, Sacramento, CA, 95616, USA.
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, UC Davis Medical Center, 4150 V Street, Suite 3500, Sacramento, CA, 95817, USA.
| | - Mohamed R Ali
- Division of Foregut, Metabolic, and General Surgery, Department of Surgery, University of California Davis, Sacramento, CA, 95616, USA
- Center for Alimentary and Metabolic Sciences, Department of Surgery, University of California, Davis, Sacramento, CA, 95616, USA
| | - Victoria Lyo
- Division of Foregut, Metabolic, and General Surgery, Department of Surgery, University of California Davis, Sacramento, CA, 95616, USA
- Center for Alimentary and Metabolic Sciences, Department of Surgery, University of California, Davis, Sacramento, CA, 95616, USA
| | - Amy Webb
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA
| | - Maciej Pietrzak
- Department of Biomedical Informatics, The Ohio State University, Columbus, OH, 43210, USA
| | - Jiangjiang Zhu
- The Department of Human Sciences, The Ohio State University, Columbus, OH, 43210, USA
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA
| | - Fouad Choueiry
- The Department of Human Sciences, The Ohio State University, Columbus, OH, 43210, USA
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA
| | - Hong Li
- The UC Davis Comprehensive Cancer Center, Sacramento, CA, 95616, USA
- Division of Biostatistics, Public Health Sciences, University of California Davis, Davis, CA, 95616, USA
| | - Bethany P Cummings
- Center for Alimentary and Metabolic Sciences, Department of Surgery, University of California, Davis, Sacramento, CA, 95616, USA
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA, 95616, USA
| | - Maria L Marco
- Department of Food Science and Technology, University of California Davis, Davis, CA, 95616, USA
| | - Valentina Medici
- Division of Gastroenterology, Department of Internal Medicine, University of California, Davis, Sacramento, CA, 95616, USA
| | - Steven K Clinton
- The Ohio State University Comprehensive Cancer Center, Columbus, OH, 43210, USA
- Division of Medical Oncology, Department of Internal Medicine, The Ohio State University, Columbus, OH, 43210, USA
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Shishani R, Wang A, Lyo V, Nandakumar R, Cummings BP. Vertical Sleeve Gastrectomy Reduces Gut Luminal Deoxycholic Acid Concentrations in Mice. Obes Surg 2024; 34:2483-2491. [PMID: 38777944 PMCID: PMC11217124 DOI: 10.1007/s11695-024-07288-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2024] [Revised: 05/13/2024] [Accepted: 05/13/2024] [Indexed: 05/25/2024]
Abstract
BACKGROUND Bariatric surgery alters bile acid metabolism, which contributes to post-operative improvements in metabolic health. However, the mechanisms by which bariatric surgery alters bile acid metabolism are incompletely defined. In particular, the role of the gut microbiome in the effects of bariatric surgery on bile acid metabolism is incompletely understood. Therefore, we sought to define the changes in gut luminal bile acid composition after vertical sleeve gastrectomy (VSG). METHODS Bile acid profile was determined by UPLC-MS/MS in serum and gut luminal samples from VSG and sham-operated mice. Sham-operated mice were divided into two groups: one was fed ad libitum, while the other was food-restricted to match their body weight to the VSG-operated mice. RESULTS VSG decreased gut luminal secondary bile acids, which was driven by a decrease in gut luminal deoxycholic acid concentrations and abundance. However, gut luminal cholic acid (precursor for deoxycholic acid) concentration and abundance did not differ between groups. Therefore, the observed decrease in gut luminal deoxycholic acid abundance after VSG was not due to a reduction in substrate availability. CONCLUSION VSG decreased gut luminal deoxycholic acid abundance independently of body weight, which may be driven by a decrease in gut bacterial bile acid metabolism.
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Affiliation(s)
- Rahaf Shishani
- Department of Surgery, Division of Foregut, Metabolic, and General Surgery, Center for Alimentary and Metabolic Sciences, School of Medicine, University of California - Davis, Sacramento, CA, 95817, USA
- Department of Molecular Biosciences, School of Veterinary Medicine, University of CA - Davis, Davis, CA, 95616, USA
| | - Annie Wang
- Department of Surgery, Division of Foregut, Metabolic, and General Surgery, Center for Alimentary and Metabolic Sciences, School of Medicine, University of California - Davis, Sacramento, CA, 95817, USA
| | - Victoria Lyo
- Department of Surgery, Division of Foregut, Metabolic, and General Surgery, Center for Alimentary and Metabolic Sciences, School of Medicine, University of California - Davis, Sacramento, CA, 95817, USA
| | - Renu Nandakumar
- Biomarkers Core Laboratory, Irving Institute for Clinical and Translational Research, Columbia University Irving Medical Center, Columbia University, New York, NY, 10032, USA
| | - Bethany P Cummings
- Department of Surgery, Division of Foregut, Metabolic, and General Surgery, Center for Alimentary and Metabolic Sciences, School of Medicine, University of California - Davis, Sacramento, CA, 95817, USA.
- Department of Molecular Biosciences, School of Veterinary Medicine, University of CA - Davis, Davis, CA, 95616, USA.
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Abuawwad M, Tibude A, Bansi D, Idris I, Madhok B. A commentary review on endoscopic sleeve gastroplasty: Indications, outcomes and future implications. Diabetes Obes Metab 2024; 26:2546-2553. [PMID: 38685614 DOI: 10.1111/dom.15613] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Revised: 04/08/2024] [Accepted: 04/09/2024] [Indexed: 05/02/2024]
Abstract
Metabolic and bariatric surgeries have been shown to be the most effective strategy to induce and maintain significant weight loss for people living with severe obesity. However, ongoing concerns regarding operative risks, irreversibility and excess costs limit their broader clinical use. Endoscopic bariatric therapies are pragmatic alternatives for patients who are not suitable for metabolic and bariatric surgeries or who are concerned regarding their long-term safety. Endoscopic sleeve gastroplasty has emerged as a novel technique of endoscopic bariatric therapies, which have garnered significant interest and evidence in the past few years. Its safety, efficacy and cost-effectiveness have been shown in various studies, while comparisons with sleeve gastrectomy have been widely made. This review brings together current evidence pertaining to the technicality of the procedure itself, current indications, safety and efficacy, cost-effectiveness, as well as its future role and development.
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Affiliation(s)
- Mahmoud Abuawwad
- East Midlands Bariatric and Metabolic Institute (EMBMI), Royal Derby Hospital, Derby, UK
- Bariatric Surgery - General Surgery Department, Royal Sunderland Hospital, Sunderland, UK
| | - Ameya Tibude
- East Midlands Bariatric and Metabolic Institute (EMBMI), Royal Derby Hospital, Derby, UK
| | - Devinder Bansi
- Honorary Clinical Senior Lecturer, Faculty of Medicine, Imperial College London, London, UK
| | - Iskandar Idris
- East Midlands Bariatric and Metabolic Institute (EMBMI), Royal Derby Hospital, Derby, UK
- MRC-Versus Arthritis Centre for Musculoskeletal Ageing Research, National Institute for Health Research Nottingham Biomedical Research Centre, Clinical, Metabolic and Molecular Physiology, University of Nottingham, Royal Derby Hospital, Derby, UK
| | - Brijesh Madhok
- East Midlands Bariatric and Metabolic Institute (EMBMI), Royal Derby Hospital, Derby, UK
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Hamamah S, Hajnal A, Covasa M. Influence of Bariatric Surgery on Gut Microbiota Composition and Its Implication on Brain and Peripheral Targets. Nutrients 2024; 16:1071. [PMID: 38613104 PMCID: PMC11013759 DOI: 10.3390/nu16071071] [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: 03/14/2024] [Revised: 03/29/2024] [Accepted: 04/02/2024] [Indexed: 04/14/2024] Open
Abstract
Obesity remains a significant global health challenge, with bariatric surgery remaining as one of the most effective treatments for severe obesity and its related comorbidities. This review highlights the multifaceted impact of bariatric surgery beyond mere physical restriction or nutrient malabsorption, underscoring the importance of the gut microbiome and neurohormonal signals in mediating the profound effects on weight loss and behavior modification. The various bariatric surgery procedures, such as Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG), act through distinct mechanisms to alter the gut microbiome, subsequently impacting metabolic health, energy balance, and food reward behaviors. Emerging evidence has shown that bariatric surgery induces profound changes in the composition of the gut microbiome, notably altering the Firmicutes/Bacteroidetes ratio and enhancing populations of beneficial bacteria such as Akkermansia. These microbiota shifts have far-reaching effects beyond gut health, influencing dopamine-mediated reward pathways in the brain and modulating the secretion and action of key gut hormones including ghrelin, leptin, GLP-1, PYY, and CCK. The resultant changes in dopamine signaling and hormone levels contribute to reduced hedonic eating, enhanced satiety, and improved metabolic outcomes. Further, post-bariatric surgical effects on satiation targets are in part mediated by metabolic byproducts of gut microbiota like short-chain fatty acids (SCFAs) and bile acids, which play a pivotal role in modulating metabolism and energy expenditure and reducing obesity-associated inflammation, as well as influencing food reward pathways, potentially contributing to the regulation of body weight and reduction in hedonic eating behaviors. Overall, a better understanding of these mechanisms opens the door to developing non-surgical interventions that replicate the beneficial effects of bariatric surgery on the gut microbiome, dopamine signaling, and gut hormone regulation, offering new avenues for obesity treatment.
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Affiliation(s)
- Sevag Hamamah
- Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 9176, USA;
| | - Andras Hajnal
- Department of Neural and Behavioral Sciences, College of Medicine, The Pennsylvania State University, Hershey, PA 17033, USA;
| | - Mihai Covasa
- Department of Basic Medical Sciences, College of Osteopathic Medicine, Western University of Health Sciences, Pomona, CA 9176, USA;
- Department of Biomedical Sciences, College of Medicine and Biological Science, University of Suceava, 7200229 Suceava, Romania
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Tsilingiris D, Kokkinos A. Advances in obesity pharmacotherapy; learning from metabolic surgery and beyond. Metabolism 2024; 151:155741. [PMID: 37995806 DOI: 10.1016/j.metabol.2023.155741] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/30/2023] [Revised: 11/05/2023] [Accepted: 11/16/2023] [Indexed: 11/25/2023]
Abstract
Currently, metabolic surgery (MS) constitutes the most effective means for durable weight loss of clinically meaningful magnitude, type 2 diabetes remission and resolution of non-alcoholic steatohepatitis, as well as other obesity-related comorbidities. Accumulating evidence on the mechanisms through which MS exerts its actions has highlighted the altered secretion of hormonally active peptides of intestinal origin with biological actions crucial to energy metabolism as key drivers of MS clinical effects. The initial success of glucagon-like peptide-1 (GLP-1) receptor agonists regarding weight loss and metabolic amelioration have been followed by the development of unimolecular dual and triple polyagonists, additionally exploiting the effects of glucagon and/or glucose-dependent insulinotropic polypeptide (GIP) which achieves a magnitude of weight loss approximating that of common MS operations. Through the implementation of such therapies, the feasibility of a "medical bypass", namely the replication of the clinical effects of MS through non-surgical interventions may be foreseeable in the near future. Apart from weight loss, this approach ought to be put to the test also regarding other clinical outcomes, such as liver steatosis and steatohepatitis, cardiovascular disease, and overall prognosis, on which MS has a robustly demonstrated impact. Besides, a medical bypass as an alternative, salvage, or combination strategy to MS may promote precision medicine in obesity therapeutics.
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Affiliation(s)
- Dimitrios Tsilingiris
- First Department of Internal Medicine, University Hospital of Alexandroupolis, Alexandroupolis, Greece
| | - Alexander Kokkinos
- 1st Department of Propaedeutic Internal Medicine, Athens University Medical School, Laiko Hospital, Athens, Greece.
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Kokkorakis M, Katsarou A, Katsiki N, Mantzoros CS. Milestones in the journey towards addressing obesity; Past trials and triumphs, recent breakthroughs, and an exciting future in the era of emerging effective medical therapies and integration of effective medical therapies with metabolic surgery. Metabolism 2023; 148:155689. [PMID: 37689110 DOI: 10.1016/j.metabol.2023.155689] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/29/2023] [Revised: 08/28/2023] [Accepted: 08/28/2023] [Indexed: 09/11/2023]
Abstract
The 21st century is characterized by an increasing incidence and prevalence of obesity and the burden of its associated comorbidities, especially cardiometabolic diseases, which are reaching pandemic proportions. In the late '90s, the "black box" of adipose tissue and energy homeostasis was opened with the discovery of leptin, transforming the adipose tissue from an "inert fat-storage organ" to the largest human endocrine organ and creating the basis on which more intensified research efforts to elucidate the pathogenesis of obesity and develop novel treatments were based upon. Even though leptin was eventually not proven to be the "standalone magic bullet" for the treatment of common/polygenic obesity, it has been successful in the treatment of monogenic obesity syndromes. Additionally, it shifted the paradigm of treating obesity from a condition due to "lack of willpower" to a disease due to distinct underlying biological mechanisms for which specific pharmacotherapies would be needed in addition to lifestyle modification. Subsequently, the melanocortin pathway proved to be an equally valuable pathway for the pharmacotherapy of obesity. Melanocortin receptor agonists have recently been approved for treating certain types of syndromic obesity. Other molecules- such as incretins, implicated in energy and glucose homeostasis- are secreted by the gastrointestinal tract. Glucagon-like peptide 1 (GLP-1) is the most prominent one, with GLP-1 analogs approved for common/polygenic obesity. Unimolecular combinations with other incretins, e.g., GLP-1 with gastric inhibitory polypeptide and/or glucagon, are expected to be approved soon as more effective pharmacotherapies for obesity and its comorbidities. Unimolecular combinations with other compounds and small molecules activating the receptors of these molecules are currently under investigation as promising future pharmacotherapies. Moreover, metabolic and bariatric surgery has also demonstrated impressive results, especially in the case of morbid obesity. Consequently, this broadening therapeutic armamentarium calls for a well-thought-after and well-coordinated multidisciplinary approach, for instance, through cardiometabolic expertise centers, that would ideally address effectively and cost-effectively obesity and its comorbidities, providing tangible benefits to large segments of the population.
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Affiliation(s)
- Michail Kokkorakis
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Angeliki Katsarou
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Niki Katsiki
- Department of Nutritional Sciences and Dietetics, International Hellenic University, 57400 Thessaloniki, Greece
| | - Christos S Mantzoros
- Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Section of Endocrinology, VA Boston Healthcare System, Harvard Medical School, Boston, MA 02115, USA.
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10
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Yin M, Wang Y, Han M, Liang R, Li S, Wang G, Gang X. Mechanisms of bariatric surgery for weight loss and diabetes remission. J Diabetes 2023; 15:736-752. [PMID: 37442561 PMCID: PMC10509523 DOI: 10.1111/1753-0407.13443] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2023] [Revised: 06/12/2023] [Accepted: 06/26/2023] [Indexed: 07/15/2023] Open
Abstract
Obesity and type 2 diabetes(T2D) lead to defects in intestinal hormones secretion, abnormalities in the composition of bile acids (BAs), increased systemic and adipose tissue inflammation, defects of branched-chain amino acids (BCAAs) catabolism, and dysbiosis of gut microbiota. Bariatric surgery (BS) has been shown to be highly effective in the treatment of obesity and T2D, which allows us to view BS not simply as weight-loss surgery but as a means of alleviating obesity and its comorbidities, especially T2D. In recent years, accumulating studies have focused on the mechanisms of BS to find out which metabolic parameters are affected by BS through which pathways, such as which hormones and inflammatory processes are altered. The literatures are saturated with the role of intestinal hormones and the gut-brain axis formed by their interaction with neural networks in the remission of obesity and T2D following BS. In addition, BAs, gut microbiota and other factors are also involved in these benefits after BS. The interaction of these factors makes the mechanisms of metabolic improvement induced by BS more complicated. To date, we do not fully understand the exact mechanisms of the metabolic alterations induced by BS and its impact on the disease process of T2D itself. This review summarizes the changes of intestinal hormones, BAs, BCAAs, gut microbiota, signaling proteins, growth differentiation factor 15, exosomes, adipose tissue, brain function, and food preferences after BS, so as to fully understand the actual working mechanisms of BS and provide nonsurgical therapeutic strategies for obesity and T2D.
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Affiliation(s)
- Mengsha Yin
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Yao Wang
- Department of OrthopedicsThe Second Hospital Jilin UniversityChangchunChina
| | - Mingyue Han
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Ruishuang Liang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Shanshan Li
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Guixia Wang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
| | - Xiaokun Gang
- Department of Endocrinology and MetabolismThe First Hospital of Jilin UniversityChangchunChina
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11
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Pérez-Rubio Á, Soluyanova P, Moro E, Quintás G, Rienda I, Periañez MD, Painel A, Vizuete J, Pérez-Rojas J, Castell JV, Trullenque-Juan R, Pareja E, Jover R. Gut Microbiota and Plasma Bile Acids Associated with Non-Alcoholic Fatty Liver Disease Resolution in Bariatric Surgery Patients. Nutrients 2023; 15:3187. [PMID: 37513605 PMCID: PMC10385764 DOI: 10.3390/nu15143187] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/29/2023] [Accepted: 07/12/2023] [Indexed: 07/30/2023] Open
Abstract
Bariatric surgery (BS) has several benefits, including resolution of non-alcoholic fatty liver disease (NAFLD) in many patients. However, a significant percentage of patients do not experience improvement in fatty liver after BS, and more than 10% develop new or worsening NAFLD features. Therefore, a question that remains unanswered is why some patients experience resolved NAFLD after BS and others do not. In this study, we investigated the fecal microbiota and plasma bile acids associated with NAFLD resolution in twelve morbidly obese patients undergoing BS, of whom six resolved their steatosis one year after surgery and another six did not. Results indicate that the hallmark of the gut microbiota in responder patients is a greater abundance of Bacteroides, Akkermansia, and several species of the Clostridia class (genera: Blautia, Faecalibacterium, Roseburia, Butyricicoccusa, and Clostridium), along with a decreased abundance of Actinomycetes/Bifidobacterium and Faecalicatena. NAFLD resolution was also associated with a sustained increase in primary bile acids (particularly non-conjugated), which likely results from a reduction in bacterial gut species capable of generating secondary bile acids. We conclude that there are specific changes in gut microbiota and plasma bile acids that could contribute to resolving NAFLD in BS patients. The knowledge acquired can help to design interventions with prebiotics and/or probiotics to promote a gut microbiome that favors NAFLD resolution.
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Affiliation(s)
- Álvaro Pérez-Rubio
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Dr. Peset, 46017 Valencia, Spain
| | - Polina Soluyanova
- Experimental Hepatology Joint Unit, Health Research Institute La Fe-University of Valencia, 46026 Valencia, Spain
- Departamento de Bioquímica y Biología Molecular, Universitat de València, 46010 Valencia, Spain
| | - Erika Moro
- Experimental Hepatology Joint Unit, Health Research Institute La Fe-University of Valencia, 46026 Valencia, Spain
- Departamento de Bioquímica y Biología Molecular, Universitat de València, 46010 Valencia, Spain
| | - Guillermo Quintás
- Health and Biomedicine, Leitat Technological Center, 08225 Terrassa, Spain
| | - Iván Rienda
- Pathology Department, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
| | - María Dolores Periañez
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Dr. Peset, 46017 Valencia, Spain
| | - Andrés Painel
- Section of Abdominal Imaging, Radiology Department, Hospital Universitario Dr. Peset, 46017 Valencia, Spain
| | - José Vizuete
- Section of Abdominal Imaging, Radiology Department, Hospital Universitario Dr. Peset, 46017 Valencia, Spain
| | - Judith Pérez-Rojas
- Pathology Department, Hospital Universitario y Politécnico La Fe, 46026 Valencia, Spain
| | - José V Castell
- Experimental Hepatology Joint Unit, Health Research Institute La Fe-University of Valencia, 46026 Valencia, Spain
- Departamento de Bioquímica y Biología Molecular, Universitat de València, 46010 Valencia, Spain
- CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain
| | - Ramón Trullenque-Juan
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Dr. Peset, 46017 Valencia, Spain
| | - Eugenia Pareja
- Servicio de Cirugía General y Aparato Digestivo, Hospital Universitario Dr. Peset, 46017 Valencia, Spain
- Experimental Hepatology Joint Unit, Health Research Institute La Fe-University of Valencia, 46026 Valencia, Spain
| | - Ramiro Jover
- Experimental Hepatology Joint Unit, Health Research Institute La Fe-University of Valencia, 46026 Valencia, Spain
- Departamento de Bioquímica y Biología Molecular, Universitat de València, 46010 Valencia, Spain
- CIBERehd, Instituto de Salud Carlos III, 28029 Madrid, Spain
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12
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Garruti G, Baj J, Cignarelli A, Perrini S, Giorgino F. Hepatokines, bile acids and ketone bodies are novel Hormones regulating energy homeostasis. Front Endocrinol (Lausanne) 2023; 14:1154561. [PMID: 37274345 PMCID: PMC10236950 DOI: 10.3389/fendo.2023.1154561] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2023] [Accepted: 04/07/2023] [Indexed: 06/06/2023] Open
Abstract
Current views show that an impaired balance partly explains the fat accumulation leading to obesity. Fetal malnutrition and early exposure to endocrine-disrupting compounds also contribute to obesity and impaired insulin secretion and/or sensitivity. The liver plays a major role in systemic glucose homeostasis through hepatokines secreted by hepatocytes. Hepatokines influence metabolism through autocrine, paracrine, and endocrine signaling and mediate the crosstalk between the liver, non-hepatic target tissues, and the brain. The liver also synthetizes bile acids (BAs) from cholesterol and secretes them into the bile. After food consumption, BAs mediate the digestion and absorption of fat-soluble vitamins and lipids in the duodenum. In recent studies, BAs act not simply as fat emulsifiers but represent endocrine molecules regulating key metabolic pathways. The liver is also the main site of the production of ketone bodies (KBs). In prolonged fasting, the brain utilizes KBs as an alternative to CHO. In the last few years, the ketogenic diet (KD) became a promising dietary intervention. Studies on subjects undergoing KD show that KBs are important mediators of inflammation and oxidative stress. The present review will focus on the role played by hepatokines, BAs, and KBs in obesity, and diabetes prevention and management and analyze the positive effects of BAs, KD, and hepatokine receptor analogs, which might justify their use as new therapeutic approaches for metabolic and aging-related diseases.
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Affiliation(s)
- Gabriella Garruti
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Jacek Baj
- Department of Anatomy, Medical University of Lublin, Lublin, Poland
| | - Angelo Cignarelli
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Sebastio Perrini
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
| | - Francesco Giorgino
- Unit of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, Department of Precision and Regenerative Medicine, University of Bari Aldo Moro, Bari, Italy
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13
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Wang M, Huang Y, Xin M, Li T, Wang X, Fang Y, Liang S, Cai T, Xu X, Dong L, Wang C, Xu Z, Song X, Li J, Zheng Y, Sun W, Li L. The impact of microbially modified metabolites associated with obesity and bariatric surgery on antitumor immunity. Front Immunol 2023; 14:1156471. [PMID: 37266441 PMCID: PMC10230250 DOI: 10.3389/fimmu.2023.1156471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2023] [Accepted: 04/24/2023] [Indexed: 06/03/2023] Open
Abstract
Obesity is strongly associated with the occurrence and development of many types of cancers. Patients with obesity and cancer present with features of a disordered gut microbiota and metabolism, which may inhibit the physiological immune response to tumors and possibly damage immune cells in the tumor microenvironment. In recent years, bariatric surgery has become increasingly common and is recognized as an effective strategy for long-term weight loss; furthermore, bariatric surgery can induce favorable changes in the gut microbiota. Some studies have found that microbial metabolites, such as short-chain fatty acids (SCFAs), inosine bile acids and spermidine, play an important role in anticancer immunity. In this review, we describe the changes in microbial metabolites initiated by bariatric surgery and discuss the effects of these metabolites on anticancer immunity. This review attempts to clarify the relationship between alterations in microbial metabolites due to bariatric surgery and the effectiveness of cancer treatment. Furthermore, this review seeks to provide strategies for the development of microbial metabolites mimicking the benefits of bariatric surgery with the aim of improving therapeutic outcomes in cancer patients who have not received bariatric surgery.
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Affiliation(s)
- Meng Wang
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Yuhong Huang
- College of Life Science, Yangtze University, Jingzhou, Hubei, China
| | - Meiling Xin
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Tianxing Li
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xueke Wang
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
- The Second Clinical Medical College, Henan University of Chinese Medicine, Zhengzhou, Henan, China
| | - Yini Fang
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
- Basic Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China
| | - Shufei Liang
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Tianqi Cai
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Xiaoxue Xu
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Ling Dong
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Chao Wang
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Zhengbao Xu
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Xinhua Song
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Jingda Li
- College of Life Science, Yangtze University, Jingzhou, Hubei, China
| | - Yanfei Zheng
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
| | - Wenlong Sun
- School of Life Sciences and Medicine, Shandong University of Technology, Zibo, Shandong, China
| | - Lingru Li
- National Institute of Traditional Chinese Medicine Constitution and Preventive Medicine, Beijing University of Chinese Medicine, Beijing, China
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14
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Louca P, Meijnikman AS, Nogal A, Asnicar F, Attaye I, Vijay A, Kouraki A, Visconti A, Wong K, Berry SE, Leeming ER, Mompeo O, Tettamanzi F, Baleanu AF, Falchi M, Hadjigeorgiou G, Wolf J, Acherman YIZ, Van de Laar AW, Gerdes VEA, Michelotti GA, Franks PW, Segata N, Mangino M, Spector TD, Bulsiewicz WJ, Nieuwdorp M, Valdes AM, Menni C. The secondary bile acid isoursodeoxycholate correlates with post-prandial lipemia, inflammation, and appetite and changes post-bariatric surgery. Cell Rep Med 2023; 4:100993. [PMID: 37023745 PMCID: PMC10140478 DOI: 10.1016/j.xcrm.2023.100993] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 10/12/2022] [Accepted: 03/14/2023] [Indexed: 04/08/2023]
Abstract
Primary and secondary bile acids (BAs) influence metabolism and inflammation, and the gut microbiome modulates levels of BAs. We systematically explore the host genetic, gut microbial, and habitual dietary contribution to a panel of 19 serum and 15 stool BAs in two population-based cohorts (TwinsUK, n = 2,382; ZOE PREDICT-1, n = 327) and assess changes post-bariatric surgery and after nutritional interventions. We report that BAs have a moderately heritable genetic component, and the gut microbiome accurately predicts their levels in serum and stool. The secondary BA isoursodeoxycholate (isoUDCA) can be explained mostly by gut microbes (area under the receiver operating characteristic curve [AUC] = ∼80%) and associates with post-prandial lipemia and inflammation (GlycA). Furthermore, circulating isoUDCA decreases significantly 1 year after bariatric surgery (β = -0.72, p = 1 × 10-5) and in response to fiber supplementation (β = -0.37, p < 0.03) but not omega-3 supplementation. In healthy individuals, isoUDCA fasting levels correlate with pre-meal appetite (p < 1 × 10-4). Our findings indicate an important role for isoUDCA in lipid metabolism, appetite, and, potentially, cardiometabolic risk.
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Affiliation(s)
- Panayiotis Louca
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Abraham S Meijnikman
- Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Ana Nogal
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | | | - Ilias Attaye
- Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Amrita Vijay
- Nottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK; Inflammation, Recovery and Injury Sciences, School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK
| | - Afroditi Kouraki
- Nottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK; Inflammation, Recovery and Injury Sciences, School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK
| | - Alessia Visconti
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Kari Wong
- Metabolon, Research Triangle Park, Morrisville, NC, USA
| | - Sarah E Berry
- Department of Nutritional Sciences, King's College London, London, UK
| | - Emily R Leeming
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Olatz Mompeo
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Francesca Tettamanzi
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Andrei-Florin Baleanu
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | - Mario Falchi
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | | | | | | | | | - Victor E A Gerdes
- Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | | | - Paul W Franks
- Lund University Diabetes Center, Lund University, Malmö, Sweden; Department of Clinical Sciences, Lund University, Malmö, Sweden
| | - Nicola Segata
- Department CIBIO, University of Trento, Trento, Italy
| | - Massimo Mangino
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK; NIHR Biomedical Research Centre at Guy's and St Thomas' Foundation Trust, SE1 9RT London, UK
| | - Tim D Spector
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK
| | | | - Max Nieuwdorp
- Department of (Experimental) Vascular Medicine, Amsterdam University Medical Centre (UMC), Amsterdam, the Netherlands
| | - Ana M Valdes
- Nottingham NIHR Biomedical Research Centre at the School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK; Inflammation, Recovery and Injury Sciences, School of Medicine, University of Nottingham, NG5 1PB Nottingham, UK.
| | - Cristina Menni
- Department of Twin Research & Genetic Epidemiology, King's College London, SE1 7EH London, UK.
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15
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Steenackers N, Vanuytsel T, Augustijns P, Deleus E, Deckers W, Deroose CM, Falony G, Lannoo M, Mertens A, Mols R, Vangoitsenhoven R, Wauters L, Van der Schueren B, Matthys C. Effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal physiology. Eur J Pharm Biopharm 2023; 183:92-101. [PMID: 36603693 DOI: 10.1016/j.ejpb.2022.12.018] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Revised: 12/07/2022] [Accepted: 12/30/2022] [Indexed: 01/03/2023]
Abstract
BACKGROUND Knowledge regarding the gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass is urgently needed to understand, prevent and treat the nutritional and pharmacological complications of bariatric surgery. AIM To investigate the effect of sleeve gastrectomy and Roux-en-Y gastric bypass on gastrointestinal motility (e.g., transit and pressure), pH, and intestinal bile acid concentration. MATERIAL AND METHODS An exploratory cross-sectional study was performed in six participants living with obesity, six participants who underwent sleeve gastrectomy, and six participants who underwent Roux-en-Y gastric bypass. During the first visit, a wireless motility capsule (SmartPill©) was ingested after an overnight fast to measure gastrointestinal transit, pH, and pressure. During the second visit, a gastric emptying scintigraphy test of a nutritional drink labeled with 99mTc-colloid by a dual-head SPECT gamma camera was performed to measure gastric emptying half-time (GET1/2). During the third visit, two customized multiple lumen aspiration catheters were positioned to collect fasting and postprandial intestinal fluids to measure bile acid concentration. RESULTS Immediate pouch emptying (P = 0.0007) and a trend for faster GET1/2 (P = 0.09) were observed in both bariatric groups. There was a tendency for a shorter orocecal transit in participants with sleeve gastrectomy and Roux-en-Y gastric bypass (P = 0.08). The orocecal segment was characterized by a higher 25th percentile pH (P = 0.004) and a trend for a higher median pH in both bariatric groups (P = 0.07). Fasting total bile acid concentration was 7.5-fold higher in the common limb after Roux-en-Y gastric bypass (P < 0.0001) and 3.5-fold higher in the jejunum after sleeve gastrectomy (P = 0.009) compared to obesity. Postprandial bile acid concentration was 3-fold higher in the jejunum after sleeve gastrectomy (P = 0.0004) and 6.5-fold higher in the common limb after Roux-en-Y gastric bypass (P < 0.0001) compared to obesity. CONCLUSION The anatomical alterations of sleeve gastrectomy and Roux-en-Y gastric bypass have an important impact on gastrointestinal physiology. This data confirms changes in transit and pH and provides the first evidence for altered intraluminal bile acid concentration.
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Affiliation(s)
- Nele Steenackers
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Patrick Augustijns
- Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Ellen Deleus
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Wies Deckers
- Nuclear Medicine, University Hospitals Leuven, Leuven, Belgium
| | | | - Gwen Falony
- Institute, Department of Microbiology and Immunology, KU Leuven, Leuven, Belgium; Center for Microbiology, VIB, Leuven, Belgium
| | - Matthias Lannoo
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Abdominal Surgery, University Hospitals Leuven, Leuven, Belgium
| | - Ann Mertens
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Raf Mols
- Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Roman Vangoitsenhoven
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Lucas Wauters
- Translational Research Center for Gastrointestinal Disorders, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium
| | - Bart Van der Schueren
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium
| | - Christophe Matthys
- Clinical and Experimental Endocrinology, Department of Chronic Diseases and Metabolism, KU Leuven, Leuven, Belgium; Department of Endocrinology, University Hospitals Leuven, Leuven, Belgium.
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16
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Maestri M, Santopaolo F, Pompili M, Gasbarrini A, Ponziani FR. Gut microbiota modulation in patients with non-alcoholic fatty liver disease: Effects of current treatments and future strategies. Front Nutr 2023; 10:1110536. [PMID: 36875849 PMCID: PMC9978194 DOI: 10.3389/fnut.2023.1110536] [Citation(s) in RCA: 39] [Impact Index Per Article: 19.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Accepted: 01/16/2023] [Indexed: 02/18/2023] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is frequently associated with metabolic disorders, being highly prevalent in obese and diabetic patients. Many concomitant factors that promote systemic and liver inflammation are involved in NAFLD pathogenesis, with a growing body of evidence highlighting the key role of the gut microbiota. Indeed, the gut-liver axis has a strong impact in the promotion of NAFLD and in the progression of the wide spectrum of its manifestations, claiming efforts to find effective strategies for gut microbiota modulation. Diet is among the most powerful tools; Western diet negatively affects intestinal permeability and the gut microbiota composition and function, selecting pathobionts, whereas Mediterranean diet fosters health-promoting bacteria, with a favorable impact on lipid and glucose metabolism and liver inflammation. Antibiotics and probiotics have been used to improve NAFLD features, with mixed results. More interestingly, medications used to treat NAFLD-associated comorbidities may also modulate the gut microbiota. Drugs for the treatment of type 2 diabetes mellitus (T2DM), such as metformin, glucagon-like peptide-1 (GLP-1) agonists, and sodium-glucose cotransporter (SGLT) inhibitors, are not only effective in the regulation of glucose homeostasis, but also in the reduction of liver fat content and inflammation, and they are associated with a shift in the gut microbiota composition towards a healthy phenotype. Even bariatric surgery significantly changes the gut microbiota, mostly due to the modification of the gastrointestinal anatomy, with a parallel improvement in histological features of NAFLD. Other options with promising effects in reprogramming the gut-liver axis, such as fecal microbial transplantation (FMT) and next-generation probiotics deserve further investigation for future inclusion in the therapeutic armamentarium of NAFLD.
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Affiliation(s)
- Marta Maestri
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Francesco Santopaolo
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy
| | - Maurizio Pompili
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Antonio Gasbarrini
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
| | - Francesca Romana Ponziani
- Internal Medicine and Gastroenterology-Hepatology Unit, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, Rome, Italy.,Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Rome, Italy
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17
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Substantial Fat Loss in Physique Competitors Is Characterized by Increased Levels of Bile Acids, Very-Long Chain Fatty Acids, and Oxylipins. Metabolites 2022; 12:metabo12100928. [PMID: 36295830 PMCID: PMC9609491 DOI: 10.3390/metabo12100928] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Revised: 09/17/2022] [Accepted: 09/22/2022] [Indexed: 11/30/2022] Open
Abstract
Weight loss and increased physical activity may promote beneficial modulation of the metabolome, but limited evidence exists about how very low-level weight loss affects the metabolome in previously non-obese active individuals. Following a weight loss period (21.1 ± 3.1 weeks) leading to substantial fat mass loss of 52% (−7.9 ± 1.5 kg) and low body fat (12.7 ± 4.1%), the liquid chromatography-mass spectrometry-based metabolic signature of 24 previously young, healthy, and normal weight female physique athletes was investigated. We observed uniform increases (FDR < 0.05) in bile acids, very-long-chain free fatty acids (FFA), and oxylipins, together with reductions in unsaturated FFAs after weight loss. These widespread changes, especially in the bile acid profile, were most strongly explained (FDR < 0.05) by changes in android (visceral) fat mass. The reported changes did not persist, as all of them were reversed after the subsequent voluntary weight regain period (18.4 ± 2.9 weeks) and were unchanged in non-dieting controls (n = 16). Overall, we suggest that the reported changes in FFA, bile acid, and oxylipin profiles reflect metabolic adaptation to very low levels of fat mass after prolonged periods of intense exercise and low-energy availability. However, the effects of the aforementioned metabolome subclass alteration on metabolic homeostasis remain controversial, and more studies are warranted to unravel the complex physiology and potentially associated health implications. In the end, our study reinforced the view that transient weight loss seems to have little to no long-lasting molecular and physiological effects.
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18
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Xia Y, Ren M, Yang J, Cai C, Cheng W, Zhou X, Lu D, Ji F. Gut microbiome and microbial metabolites in NAFLD and after bariatric surgery: Correlation and causality. Front Microbiol 2022; 13:1003755. [PMID: 36204626 PMCID: PMC9531827 DOI: 10.3389/fmicb.2022.1003755] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
Non-alcoholic fatty liver disease (NAFLD) is currently related to a heavy socioeconomic burden and increased incidence. Since obesity is the most prevalent risk factor for NAFLD, weight loss is an effective therapeutic solution. Bariatric surgery (BS), which can achieve long-term weight loss, improves the overall health of patients with NAFLD. The two most common surgeries are the Roux-en-Y gastric bypass and sleeve gastrectomy. The gut-liver axis is the complex network of cross-talking between the gut, its microbiome, and the liver. The gut microbiome, involved in the homeostasis of the gut-liver axis, is believed to play a significant role in the pathogenesis of NAFLD and the metabolic improvement after BS. Alterations in the gut microbiome in NAFLD have been confirmed compared to that in healthy individuals. The mechanisms linking the gut microbiome to NAFLD have been proposed, including increased intestinal permeability, higher energy intake, and other pathophysiological alterations. Interestingly, several correlation studies suggested that the gut microbial signatures after BS become more similar to those of lean, healthy controls than that of patients with NAFLD. The resolution of NAFLD after BS is related to changes in the gut microbiome and its metabolites. However, confirming a causal link remains challenging. This review summarizes characteristics of the gut microbiome in patients with NAFLD before and after BS and accumulates existing evidence about the underlying mechanisms of the gut microbiome.
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Affiliation(s)
- Yi Xia
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Mengting Ren
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jinpu Yang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Changzhou Cai
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Weixin Cheng
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xinxin Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Dan Lu
- Department of Endoscopy Center, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Feng Ji
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
- *Correspondence: Feng Ji,
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19
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Abduljabbar MH, Nafea OE, Alahmari WM, Alharthi AA, Alorabi AS, Alharthi SJ, Alosami NA, Larbi N, Alshareef K. Glycemic control after sleeve gastrectomy in Taif Hospitals, Kingdom of Saudi Arabia. ALL LIFE 2022. [DOI: 10.1080/26895293.2022.2078895] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/18/2022] Open
Affiliation(s)
- Maram H. Abduljabbar
- Department of Pharmacology and Toxicology, Collage of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Ola E. Nafea
- Department of Clinical Pharmacy, Collage of Pharmacy, Taif University, Taif, Saudi Arabia
| | - Wafa M. Alahmari
- Pharm D, College of Pharmacy, Taif University, Taif, Saudi Arabia
| | | | | | | | - Norah A. Alosami
- Pharm D, College of Pharmacy, Taif University, Taif, Saudi Arabia
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20
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Martinou E, Stefanova I, Iosif E, Angelidi AM. Neurohormonal Changes in the Gut-Brain Axis and Underlying Neuroendocrine Mechanisms following Bariatric Surgery. Int J Mol Sci 2022; 23:3339. [PMID: 35328759 PMCID: PMC8954280 DOI: 10.3390/ijms23063339] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 03/15/2022] [Accepted: 03/16/2022] [Indexed: 02/05/2023] Open
Abstract
Obesity is a complex, multifactorial disease that is a major public health issue worldwide. Currently approved anti-obesity medications and lifestyle interventions lack the efficacy and durability needed to combat obesity, especially in individuals with more severe forms or coexisting metabolic disorders, such as poorly controlled type 2 diabetes. Bariatric surgery is considered an effective therapeutic modality with sustained weight loss and metabolic benefits. Numerous genetic and environmental factors have been associated with the pathogenesis of obesity, while cumulative evidence has highlighted the gut-brain axis as a complex bidirectional communication axis that plays a crucial role in energy homeostasis. This has led to increased research on the roles of neuroendocrine signaling pathways and various gastrointestinal peptides as key mediators of the beneficial effects following weight-loss surgery. The accumulate evidence suggests that the development of gut-peptide-based agents can mimic the effects of bariatric surgery and thus is a highly promising treatment strategy that could be explored in future research. This article aims to elucidate the potential underlying neuroendocrine mechanisms of the gut-brain axis and comprehensively review the observed changes of gut hormones associated with bariatric surgery. Moreover, the emerging role of post-bariatric gut microbiota modulation is briefly discussed.
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Affiliation(s)
- Eirini Martinou
- Department of Upper Gastrointestinal Surgery, Frimley Health NHS Foundation Trust, Camberley GU16 7UJ, UK;
- Faculty of Health and Medical Sciences, University of Surrey, Guildford GU2 7XH, UK
| | - Irena Stefanova
- Department of General Surgery, Frimley Health NHS Foundation Trust, Camberley GU16 7UJ, UK;
| | - Evangelia Iosif
- Department of General Surgery, Royal Surrey County Hospital, Guildford GU2 7XX, UK;
| | - Angeliki M. Angelidi
- Division of Endocrinology, Boston Children’s Hospital, Harvard Medical School, Boston, MA 02115, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
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21
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Camastra S, Palumbo M, Santini F. Nutrients handling after bariatric surgery, the role of gastrointestinal adaptation. Eat Weight Disord 2022; 27:449-461. [PMID: 33895917 PMCID: PMC8933374 DOI: 10.1007/s40519-021-01194-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2020] [Accepted: 04/10/2021] [Indexed: 01/19/2023] Open
Abstract
Bariatric surgery determines a rearrangement of the gastrointestinal tract that influences nutrient handling and plays a role in the metabolic changes observed after surgery. Most of the changes depend on the accelerated gastric emptying observed in Roux-en-Y gastric bypass (RYGB) and, to a lesser extent, in sleeve gastrectomy (SG). The rapid delivery of meal into the jejunum, particularly after RYGB, contributes to the prompt appearance of glucose in peripheral circulation. Glucose increase is the principal determinant of GLP-1 increase with the consequent stimulation of insulin secretion, the latter balanced by a paradoxical glucagon increase that stimulates EGP to prevent hypoglycaemia. Protein digestion and amino acid absorption appear accelerated after RYGB but not after SG. After RYGB, the adaptation of the gut to the new condition participates to the metabolic change. The intestinal transit is delayed, the gut microbioma is changed, the epithelium becomes hypertrophic and increases the expression of glucose transporter and of the number of cell secreting hormones. These changes are not observed after SG. After RYGB-less after SG-bile acids (BA) increase, influencing glucose metabolism probably modulating FXR and TGR5 with an effect on insulin sensitivity. Muscle, hepatic and adipose tissue insulin sensitivity improve, and the gut reinforces the recovery of IS by enhancing glucose uptake and through the effect of the BA. The intestinal changes observed after RYGB result in a light malabsorption of lipid but not of carbohydrate and protein. In conclusion, functional and morphological adaptations of the gut after RYGB and SG activate inter-organs cross-talk that modulates the metabolic changes observed after surgery.Level of evidence Level V, narrative literature review.
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Affiliation(s)
- Stefania Camastra
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy. .,Interdepartmental Research Center "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy.
| | - Maria Palumbo
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy
| | - Ferruccio Santini
- Department of Clinical and Experimental Medicine, University of Pisa, Via Roma, 67, 56126, Pisa, Italy.,Interdepartmental Research Center "Nutraceuticals and Food for Health", University of Pisa, Pisa, Italy
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22
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Martínez-Montoro JI, Kuchay MS, Balaguer-Román A, Martínez-Sánchez MA, Frutos MD, Fernández-García JC, Ramos-Molina B. Gut microbiota and related metabolites in the pathogenesis of nonalcoholic steatohepatitis and its resolution after bariatric surgery. Obes Rev 2022; 23:e13367. [PMID: 34729904 DOI: 10.1111/obr.13367] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2021] [Revised: 09/06/2021] [Accepted: 09/06/2021] [Indexed: 12/17/2022]
Abstract
Nonalcoholic fatty liver disease (NAFLD) is increasing in parallel with the rising prevalence of obesity, leading to major health and socioeconomic consequences. To date, the most effective therapeutic approach for NAFLD is weight loss. Accordingly, bariatric surgery (BS), which produces marked reductions in body weight, is associated with significant histopathological improvements in advanced stages of NAFLD, such as nonalcoholic steatohepatitis (NASH) and liver fibrosis. BS is also associated with substantial taxonomical and functional alterations in gut microbiota, which are believed to play a significant role in metabolic improvement after BS. Interestingly, gut microbiota and related metabolites may be implicated in the pathogenesis of NAFLD through diverse mechanisms, including specific microbiome signatures, short chain fatty acid production or the modulation of one-carbon metabolism. Moreover, emerging evidence highlights the potential association between gut microbiota changes after BS and NASH resolution. In this review, we summarize the current knowledge on the relationship between NAFLD severity and gut microbiota, as well as the role of the gut microbiome and related metabolites in NAFLD improvement after BS.
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Affiliation(s)
- José Ignacio Martínez-Montoro
- Department of Endocrinology and Nutrition, Virgen de la Victoria University Hospital, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain
| | - Mohammad Shafi Kuchay
- Division of Endocrinology and Diabetes, Medanta - The Medicity Hospital, Gurugram, Haryana, India
| | - Andrés Balaguer-Román
- Department of General and Digestive System Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain.,Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain
| | | | - María Dolores Frutos
- Department of General and Digestive System Surgery, Virgen de la Arrixaca University Hospital, Murcia, Spain
| | - José Carlos Fernández-García
- Department of Endocrinology and Nutrition, Regional University Hospital of Malaga, Institute of Biomedical Research in Malaga (IBIMA), Faculty of Medicine, University of Malaga, Malaga, Spain
| | - Bruno Ramos-Molina
- Obesity and Metabolism Laboratory, Biomedical Research Institute of Murcia (IMIB-Arrixaca), Murcia, Spain
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23
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de Lucena AVS, Cordeiro GG, Leão LHA, Kreimer F, de Siqueira LT, da Conti Oliveira Sousa G, de Lucena LHS, Ferraz ÁAB. Cholecystectomy Concomitant with Bariatric Surgery: Safety and Metabolic Effects. Obes Surg 2022; 32:1093-1102. [PMID: 35064462 DOI: 10.1007/s11695-022-05889-1] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Revised: 01/02/2022] [Accepted: 01/11/2022] [Indexed: 11/29/2022]
Abstract
BACKGROUND Obesity and fast weight loss in the postoperative period of bariatric surgery increase significantly the risk of cholelithiasis. Moreover, emerging evidence has pointed out the role of bile acids as possible metabolism and weight loss enhancers. This study aims to analyze the influence of cholecystectomy (CL) concomitant with bariatric surgery on weight loss, metabolic repercussions, and postoperative morbidity. STUDY DESIGN Retrospective cohort study. A total of 363 medical records were analyzed between 2002 and 2017, with 255 patients divided into four groups: with concomitant CL: sleeve gastrectomy (SG + CL group) and Roux-en-Y gastric bypass (GB + CL group); without concomitant CL: sleeve gastrectomy (SG group) and RYGB (GB group). RESULTS CL concomitant with bariatric surgery is not related to worse long-term metabolic outcomes when compared to isolated bariatric surgery. In the postoperative follow-up of the isolated bariatric surgeries, 18 (16.5%) patients underwent cholecystectomy. There was no statistical difference between the groups regarding post-surgical complications. CONCLUSION CL did not lead to worse metabolic outcomes and was also not related to a higher incidence of postoperative complications. Cholelithiasis and cholecystitis are important concerns in the postoperative period of bariatric surgery and a careful evaluation of the concomitant procedure should be performed.
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Affiliation(s)
| | - Gabriel Guerra Cordeiro
- Medical School, Federal University of Pernambuco, Av. Prof. Moraes Rego, 1235, Recife, PE, 50670-901, Brazil.
| | | | - Flávio Kreimer
- Department of Surgery, Federal University of Pernambuco, Recife, PE, Brazil
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24
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Seyfried F, Phetcharaburanin J, Glymenaki M, Nordbeck A, Hankir M, Nicholson JK, Holmes E, Marchesi JR, Li JV. Roux-en-Y gastric bypass surgery in Zucker rats induces bacterial and systemic metabolic changes independent of caloric restriction-induced weight loss. Gut Microbes 2022; 13:1-20. [PMID: 33535876 PMCID: PMC7872092 DOI: 10.1080/19490976.2021.1875108] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023] Open
Abstract
Mechanisms of Roux-en-Y gastric bypass (RYGB) surgery are not fully understood. This study aimed to investigate weight loss-independent bacterial and metabolic changes, as well as the absorption of bacterial metabolites and bile acids through the hepatic portal system following RYGB surgery. Three groups of obese Zucker (fa/fa) rats were included: RYGB (n = 11), sham surgery and body weight matched with RYGB (Sham-BWM, n = 5), and sham surgery fed ad libitum (Sham-obese, n = 5). Urine and feces were collected at multiple time points, with portal vein and peripheral blood obtained at the end of the study. Metabolic phenotyping approaches and 16S rRNA gene sequencing were used to determine the biochemical and bacterial composition of the samples, respectively. RYGB surgery-induced distinct metabolic and bacterial disturbances, which were independent of weight loss through caloric restriction. RYGB resulted in lower absorption of phenylalanine and choline, and higher urinary concentrations of host-bacterial co-metabolites (e.g., phenylacetylglycine, indoxyl sulfate), together with higher fecal trimethylamine, suggesting enhanced bacterial aromatic amino acid and choline metabolism. Short chain fatty acids (SCFAs) were lower in feces and portal vein blood from RYGB group compared to Sham-BWM, accompanied with lower abundances of Lactobacillaceae, and Ruminococcaceae known to contain SCFA producers, indicating reduced bacterial fiber fermentation. Fecal γ-amino butyric acid (GABA) was found in higher concentrations in RYGB than that in Sham groups and could play a role in the metabolic benefits associated with RYGB surgery. While no significant difference in urinary BA excretion, RYGB lowered both portal vein and circulating BA compared to Sham groups. These findings provide a valuable resource for how dynamic, multi-systems changes impact on overall metabolic health, and may provide potential therapeutic targets for developing downstream non-surgical treatment for metabolic disease.
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Affiliation(s)
- Florian Seyfried
- Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Jutarop Phetcharaburanin
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK,Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
| | - Maria Glymenaki
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK
| | - Arno Nordbeck
- Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Mohammed Hankir
- Department of General, Visceral, Transplant, Vascular, and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, Germany
| | - Jeremy K Nicholson
- Division of Organisms and Environment, School of Biosciences, Institute of Health Futures, Murdoch University, Perth, Western Australia, Australia
| | - Elaine Holmes
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK,Division of Organisms and Environment, School of Biosciences, Institute of Health Futures, Murdoch University, Perth, Western Australia, Australia
| | - Julian R. Marchesi
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK,School of Biosciences, Cardiff University, Cardiff, UK
| | - Jia V. Li
- Department of Metabolism Digestion and Reproduction, Faculty of Medicine, Imperial College LondonLondon, UK,CONTACT Jia V. Li Department of Metabolism, Digestion and Reproduction, Faculty of Medicine, Imperial College London, London, United Kingdom
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25
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Akalestou E, Miras AD, Rutter GA, le Roux CW. Mechanisms of Weight Loss After Obesity Surgery. Endocr Rev 2022; 43:19-34. [PMID: 34363458 PMCID: PMC8755990 DOI: 10.1210/endrev/bnab022] [Citation(s) in RCA: 60] [Impact Index Per Article: 20.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Indexed: 02/07/2023]
Abstract
Obesity surgery remains the most effective treatment for obesity and its complications. Weight loss was initially attributed to decreased energy absorption from the gut but has since been linked to reduced appetitive behavior and potentially increased energy expenditure. Implicated mechanisms associating rearrangement of the gastrointestinal tract with these metabolic outcomes include central appetite control, release of gut peptides, change in microbiota, and bile acids. However, the exact combination and timing of signals remain largely unknown. In this review, we survey recent research investigating these mechanisms, and seek to provide insights on unanswered questions over how weight loss is achieved following bariatric surgery which may eventually lead to safer, nonsurgical weight-loss interventions or combinations of medications with surgery.
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Affiliation(s)
- Elina Akalestou
- Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Alexander D Miras
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Guy A Rutter
- Section of Cell Biology and Functional Genomics, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK.,Lee Kong Chian Imperial Medical School, Nanyang Technological University, Singapore.,University of Montreal Hospital Research Centre, Montreal, QC, Canada
| | - Carel W le Roux
- Diabetes Complications Research Centre, University College Dublin, Ireland.,Diabetes Research Group, School of Biomedical Science, Ulster University, Belfast, UK
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26
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Yang C, Brecht J, Weiß C, Reissfelder C, Otto M, Buchwald JN, Vassilev G. Serum Glucagon, Bile Acids, and FGF-19: Metabolic Behavior Patterns After Roux-en-Y Gastric Bypass and Vertical Sleeve Gastrectomy. Obes Surg 2021; 31:4939-4946. [PMID: 34471996 DOI: 10.1007/s11695-021-05677-3] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 08/14/2021] [Accepted: 08/19/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Metabolic/bariatric surgery is a highly effective treatment for obesity and metabolic diseases. Serum glucagon, bile acids, and FGF-19 are key effectors of various metabolic processes and may play central roles in bariatric surgical outcomes. It is unclear whether these factors behave similarly after Roux-en-Y gastric bypass (RYGB) vs vertical sleeve gastrectomy (VSG). METHODS Serum glucagon, bile acids (cholic acid [CA], chenodeoxycholic acid [CDCA], deoxycholic acid [DCA]), and FGF-19 were analyzed in samples of fasting blood collected before bariatric surgery, on postoperative days 2 and 10, and at 3- and 6-month follow-up. RESULTS From September 2016 to July 2017, patients with obesity underwent RYGB or VSG; 42 patients (RYGB n = 21; VSG n = 21) were included in the analysis. In the RYGB group, glucagon, CA, and CDCA increased continuously after surgery (p = 0.0003, p = 0.0009, p = 0.0001, respectively); after an initial decrease (p = 0.04), DCA increased significantly (p = 0.0386). Serum FGF-19 was unchanged. In the VSG group, glucagon increased on day 2 (p = 0.0080), but decreased over the 6-month study course (p = 0.0025). Primary BAs (CA and CDCA) decreased immediately after surgery (p = 0.0016, p = 0.0091) and then rose (p = 0.0350, p = 0.0350); DCA followed the curve of the primary BAs until it fell off at 6 months (p = 0.0005). VSG group serum FGF-19 trended upward. CONCLUSION RYGB and VSG involve different surgical techniques and final anatomical configurations. Between postoperative day 2 and 6-month follow-up, RYGB and VSG resulted in divergent patterns of change in serum glucagon, bile acids, and FGF-19.
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Affiliation(s)
- Cui Yang
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Julia Brecht
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Christel Weiß
- Department of Medical Statistics and Biomathematics, Medical Faculty Mannheim, Heidelberg University, 68167, Mannheim, Germany
| | - Christoph Reissfelder
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Mirko Otto
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany
| | - Jane N Buchwald
- Division of Scientific Research Writing, Medwrite Medical Communications, Maiden Rock, WI, 54750, USA
| | - Georgi Vassilev
- Department of Surgery, University Medicine Mannheim, Medical Faculty Mannheim, University of Heidelberg, Theodor-Kutzer-Ufer 1-3, 68167, Mannheim, Germany.
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27
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Brown RM, Guerrero-Hreins E, Brown WA, le Roux CW, Sumithran P. Potential gut-brain mechanisms behind adverse mental health outcomes of bariatric surgery. Nat Rev Endocrinol 2021; 17:549-559. [PMID: 34262156 DOI: 10.1038/s41574-021-00520-2] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/03/2021] [Indexed: 02/06/2023]
Abstract
Bariatric surgery induces sustained weight loss and metabolic benefits via notable effects on the gut-brain axis that lead to alterations in the neuroendocrine regulation of appetite and glycaemia. However, in a subset of patients, bariatric surgery is associated with adverse effects on mental health, including increased risk of suicide or self-harm as well as the emergence of depression and substance use disorders. The contributing factors behind these adverse effects are not well understood. Accumulating evidence indicates that there are important links between gut-derived hormones, microbial and bile acid profiles, and disorders of mood and substance use, which warrant further exploration in the context of changes in gut-brain signalling after bariatric surgery. Understanding the basis of these adverse effects is essential in order to optimize the health and well-being of people undergoing treatment for obesity.
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Affiliation(s)
- Robyn M Brown
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
- Department of Biochemistry and Pharmacology, School of Biomedical Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Eva Guerrero-Hreins
- Florey Institute of Neuroscience and Mental Health, University of Melbourne, Parkville, Victoria, Australia
- Department of Biochemistry and Pharmacology, School of Biomedical Sciences, University of Melbourne, Parkville, Victoria, Australia
| | - Wendy A Brown
- Department of Surgery, Central Clinical School, Monash University, Alfred Hospital, Melbourne, Victoria, Australia
| | - Carel W le Roux
- Diabetes Complications Research Centre, Conway Institute, School of Medicine and Medical Sciences, University College, Dublin, Ireland
| | - Priya Sumithran
- Department of Medicine (St Vincent's), University of Melbourne, Melbourne, Victoria, Australia.
- Department of Endocrinology, Austin Health, Melbourne, Victoria, Australia.
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28
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Jin ZL, Liu W. Progress in treatment of type 2 diabetes by bariatric surgery. World J Diabetes 2021; 12:1187-1199. [PMID: 34512886 PMCID: PMC8394224 DOI: 10.4239/wjd.v12.i8.1187] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/17/2021] [Revised: 03/29/2021] [Accepted: 07/06/2021] [Indexed: 02/06/2023] Open
Abstract
The incidence of type 2 diabetes (T2D) is increasing at an alarming rate worldwide. Bariatric surgical procedures, such as the vertical sleeve gastrectomy and Roux-en-Y gastric bypass, are the most efficient approaches to obtain substantial and durable remission of T2D. The benefits of bariatric surgery are realized through the consequent increased satiety and alterations in gastrointestinal hormones, bile acids, and the intestinal microbiota. A comprehensive understanding of the mechanisms by which various bariatric surgical procedures exert their benefits on T2D could contribute to the design of better non-surgical treatments for T2D. In this review, we describe the classification and evolution of bariatric surgery and explore the multiple mechanisms underlying the effect of bariatric surgery on insulin resistance. Based upon our summarization of the current knowledge on the underlying mechanisms, we speculate that the gut might act as a new target for improving T2D. Our ultimate goal with this review is to provide a better understanding of T2D pathophysiology in order to support development of T2D treatments that are less invasive and more scalable.
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Affiliation(s)
- Zhang-Liu Jin
- Department of General Surgery & Department of Biliopancreatic and Metabolic Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
| | - Wei Liu
- Department of General Surgery & Department of Biliopancreatic and Metabolic Surgery, The Second Xiangya Hospital, Central South University, Changsha 410011, Hunan Province, China
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29
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Nogueiras R. MECHANISMS IN ENDOCRINOLOGY: The gut-brain axis: regulating energy balance independent of food intake. Eur J Endocrinol 2021; 185:R75-R91. [PMID: 34260412 PMCID: PMC8345901 DOI: 10.1530/eje-21-0277] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/18/2021] [Accepted: 07/14/2021] [Indexed: 12/15/2022]
Abstract
Obesity is a global pandemic with a large health and economic burden worldwide. Bodyweight is regulated by the ability of the CNS, and especially the hypothalamus, to orchestrate the function of peripheral organs that play a key role in metabolism. Gut hormones play a fundamental role in the regulation of energy balance, as they modulate not only feeding behavior but also energy expenditure and nutrient partitioning. This review examines the recent discoveries about hormones produced in the stomach and gut, which have been reported to regulate food intake and energy expenditure in preclinical models. Some of these hormones act on the hypothalamus to modulate thermogenesis and adiposity in a food intake-independent fashion. Finally, the association of these gut hormones to eating, energy expenditure, and weight loss after bariatric surgery in humans is discussed.
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Affiliation(s)
- Ruben Nogueiras
- Department of Physiology, CIMUS, USC, CIBER Fisiopatología Obesidad y Nutrición (CiberOBN), Instituto Salud Carlos III, Galician Agency of Innovation, Xunta de Galicia, Santiago de Compostela, Spain
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30
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Vertical sleeve gastrectomy confers metabolic improvements by reducing intestinal bile acids and lipid absorption in mice. Proc Natl Acad Sci U S A 2021; 118:2019388118. [PMID: 33526687 DOI: 10.1073/pnas.2019388118] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023] Open
Abstract
Vertical sleeve gastrectomy (VSG) is one of the most effective and durable therapies for morbid obesity and its related complications. Although bile acids (BAs) have been implicated as downstream mediators of VSG, the specific mechanisms through which BA changes contribute to the metabolic effects of VSG remain poorly understood. Here, we confirm that high fat diet-fed global farnesoid X receptor (Fxr) knockout mice are resistant to the beneficial metabolic effects of VSG. However, the beneficial effects of VSG were retained in high fat diet-fed intestine- or liver-specific Fxr knockouts, and VSG did not result in Fxr activation in the liver or intestine of control mice. Instead, VSG decreased expression of positive hepatic Fxr target genes, including the bile salt export pump (Bsep) that delivers BAs to the biliary pathway. This reduced small intestine BA levels in mice, leading to lower intestinal fat absorption. These findings were verified in sterol 27-hydroxylase (Cyp27a1) knockout mice, which exhibited low intestinal BAs and fat absorption and did not show metabolic improvements following VSG. In addition, restoring small intestinal BA levels by dietary supplementation with taurocholic acid (TCA) partially blocked the beneficial effects of VSG. Altogether, these findings suggest that reductions in intestinal BAs and lipid absorption contribute to the metabolic benefits of VSG.
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Abstract
PURPOSE OF REVIEW Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the United States and increasing globally. The progressive form of NAFLD, nonalcoholic steatohepatitis (NASH), can lead to cirrhosis and complications of end-stage liver disease. No FDA-approved therapy for NAFLD/NASH exists. Treatment of NAFLD/NASH includes effective and sustained life-style modification and weight loss. This review reports on the recent findings of bariatric surgery in the management of NASH. RECENT FINDINGS NAFLD, at all stages, is common in those who meet indication for bariatric surgery. Bariatric surgery resolves NAFLD/NASH and reverses early stages of fibrosis. Although randomized controlled trials of bariatric surgery in NASH are infeasible, studies defining the metabolic changes induced by bariatric surgery, and their effect on NASH, provide insight for plausible pharmacologic targets for the nonsurgical treatment of NASH. SUMMARY Resolution of NASH and fibrosis regression can occur after bariatric surgery. Although the exact mechanism(s) underlying the improvement of NASH and hepatic fibrosis following bariatric surgery is not fully elucidated, emerging data on this topic is vitally important for lending insight into the pharmacotherapies for NASH for patients who are not otherwise suitable candidates for bariatric surgery.
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Mazzini GS, Khoraki J, Browning MG, Wu J, Zhou H, Price ET, Wolfe LG, Mangino MJ, Campos GM. Gastric Bypass Increases Circulating Bile Acids and Activates Hepatic Farnesoid X Receptor (FXR) but Requires Intact Peroxisome Proliferator Activator Receptor Alpha (PPARα) Signaling to Significantly Reduce Liver Fat Content. J Gastrointest Surg 2021; 25:871-879. [PMID: 33555523 DOI: 10.1007/s11605-021-04908-3] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Accepted: 01/06/2021] [Indexed: 01/31/2023]
Abstract
BACKGROUND We interrogate effects of gastric bypass (RYGB), compared with a low-calorie diet, on bile acid (BA), liver fat, and FXR, PPARα, and targets in rats with obesity and non-alcoholic fatty liver disease (NAFLD). METHODS Male Wistar rats received a high-fat diet (obese/NAFLD, n=24) or standard chow (lean, n=8) for 12 weeks. Obese/NAFLD rats had RYGB (n=11), sham operation pair-fed to RYGB (pair-fed sham, n=8), or sham operation (sham, n=5). Lean rats had sham operation (lean sham, n=8). Post-operatively, five RYGB rats received PPARα antagonist GW6417. Sacrifice occurred at 7 weeks. We measured weight changes, fasting total plasma BA, and liver % steatosis, triglycerides, and mRNA expression of the nuclear receptors FXR, PPARα, and their targets SHP and CPT-I. RESULTS At sacrifice, obese sham was heavier (p<0.01) than all other groups that had lost similar weight loss. Obese sham had lower BA levels and lower hepatic FXR, SHP, and CPT-I mRNA expression than lean sham (P<0.05, for all comparisons). RYGB had increased BA levels compared with obese and pair-fed sham (P<0.05, for both), while pair-fed sham had BA levels, similar to obese sham. Compared with pair-fed sham, RYGB animals had increased liver FXR and PPARα expression and signaling (P<0.05). Percentage of steatosis was lower in RYGB and lean sham, relative to obese and pair-fed sham (P<0.05, for all comparisons). PPARα inhibition after RYGB resulted in similar weight loss but higher liver triglyceride content (P=0.01) compared with RYGB alone. CONCLUSIONS RYGB led to greater liver fat loss than low-calorie diet, an effect associated to increased fasting BA levels and increased expression of modulators of liver fat oxidation, FXR, and PPARα. However, intact PPARα signaling was necessary for resolution of NAFLD after RYGB.
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Affiliation(s)
- Guilherme S Mazzini
- Division of Bariatric and Gastrointestinal Surgery, Department of Surgery, Virginia Commonwealth University, 1200 E. Broad Street, Richmond, VA, USA
- Division of Gastrointestinal Surgery, Hospital de Clínicas de Porto Alegre, 2350 Ramiro Barcelos Street, Porto Alegre, RS, Brazil
| | - Jad Khoraki
- Division of Bariatric and Gastrointestinal Surgery, Department of Surgery, Virginia Commonwealth University, 1200 E. Broad Street, Richmond, VA, USA
| | - Matthew G Browning
- Division of Bariatric and Gastrointestinal Surgery, Department of Surgery, Virginia Commonwealth University, 1200 E. Broad Street, Richmond, VA, USA
| | - Jilin Wu
- Division of Bariatric and Gastrointestinal Surgery, Department of Surgery, Virginia Commonwealth University, 1200 E. Broad Street, Richmond, VA, USA
| | - Huiping Zhou
- Central Virginia Veterans Affairs Health Care System, Department of Microbiology and Immunology, Virginia Commonwealth University, 1220 E. Broad Street, Richmond, VA, USA
| | - Elvin T Price
- Department of Pharmacotherapy & Outcomes Science, School of Pharmacy, Virginia Commonwealth University, 410 N 12th Street, Richmond, VA, USA
| | - Luke G Wolfe
- Division of Bariatric and Gastrointestinal Surgery, Department of Surgery, Virginia Commonwealth University, 1200 E. Broad Street, Richmond, VA, USA
| | - Martin J Mangino
- Division of Bariatric and Gastrointestinal Surgery, Department of Surgery, Virginia Commonwealth University, 1200 E. Broad Street, Richmond, VA, USA
| | - Guilherme M Campos
- Division of Bariatric and Gastrointestinal Surgery, Department of Surgery, Virginia Commonwealth University, 1200 E. Broad Street, Richmond, VA, USA.
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Berkovskaya MA, Sych YP, Gurova OY, Fadeev VV. Significance of intestinal microbiota in implementing metabolic effects of bariatric surgery. RUSSIAN OPEN MEDICAL JOURNAL 2021. [DOI: 10.15275/rusomj.2021.0112] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022] Open
Abstract
Bariatric surgery is among successful methods of obesity treatment, with effects going beyond weight reduction alone, but rather involving improved glucose tolerance, along with control or remission of the type 2 diabetes mellitus. The precise mechanisms causing metabolic effects of bariatric surgery are not fully elucidated, even though substantial evidence suggest that they include changes in the gut microbiota, bile acid homeostasis, and the close interactions of these factors.
Intestinal microflora is directly involved in the energy metabolism of a host human. Obesity and type 2 diabetes mellitus are associated with certain changes in the species composition and diversity of intestinal microflora, which are considered important factors in the development and progression of these ailments. Bariatric surgery leads to significant and persistent changes in the composition of the intestinal microbiota, often bringing it closer to the characteristics of the microbiota of an average person with a normal weight. An important role in implementing the metabolic effects of bariatric surgery, primarily in the improvement of glucose metabolism, belongs to postoperative changes in homeostasis of bile acids. These changes imply close metabolism. Moreover, changes in the bile acid metabolism after bariatric surgery affect the microbiota of the host. Further study of these relationships would clarify the mechanisms underlying metabolic surgery, make it more predictable, targeted and controlled, as well as open new therapeutic targets in the treatment of obesity and associated conditions.
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Affiliation(s)
| | - Yulia P. Sych
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Olesya Yu. Gurova
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
| | - Valentin V. Fadeev
- I.M. Sechenov First Moscow State Medical University (Sechenov University)
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FXR in liver physiology: Multiple faces to regulate liver metabolism. Biochim Biophys Acta Mol Basis Dis 2021; 1867:166133. [PMID: 33771667 DOI: 10.1016/j.bbadis.2021.166133] [Citation(s) in RCA: 88] [Impact Index Per Article: 22.0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Revised: 03/11/2021] [Accepted: 03/17/2021] [Indexed: 12/15/2022]
Abstract
The liver is the central metabolic hub which coordinates nutritional inputs and metabolic outputs. Food intake releases bile acids which can be sensed by the bile acid receptor FXR in the liver and the intestine. Hepatic and intestinal FXR coordinately regulate postprandial nutrient disposal in a network of interacting metabolic nuclear receptors. In this review we summarize and update the "classical roles" of FXR as a central integrator of the feeding state response, which orchestrates the metabolic processing of carbohydrates, lipids, proteins and bile acids. We also discuss more recent and less well studied FXR effects on amino acid, protein metabolism, autophagic turnover and inflammation. In addition, we summarize the recent understanding of how FXR signaling is affected by posttranslational modifications and by different FXR isoforms. These modifications and variations in FXR signaling might be considered when FXR is targeted pharmaceutically in clinical applications.
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Salman AA, Salman MA, Marie MA, Rabiee A, Helmy MY, Tourky MS, Qassem MG, Shaaban HED, Sarhan MD. Factors associated with resolution of type-2 diabetes mellitus after sleeve gastrectomy in obese adults. Sci Rep 2021; 11:6002. [PMID: 33727637 PMCID: PMC7966796 DOI: 10.1038/s41598-021-85450-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2021] [Accepted: 03/01/2021] [Indexed: 02/06/2023] Open
Abstract
Many bariatric procedures are more effective for improving type-2 diabetes mellitus (T2DM) than conventional pharmacotherapy. The current research evaluated factors linked to complete and partial remission or improvement of T2DM after laparoscopic sleeve gastrectomy (LSG). The current prospective study included all diabetic patients who were submitted LSG between January 2015 and June 2018 and completed a 2-year follow-up period. Patients were assessed at baseline and 2 years after LSG. This work comprised of 226 diabetic cases. Two years after LSG, 86 patients (38.1%) achieved complete remission of DM, and 24 (10.6%) reached partial remission. Only 14 patients (6.2%) showed no change in their diabetic status. On univariate analysis, age ≤ 45 years, duration of diabetes ≤ 5 years, use of a single oral antidiabetic, HbA1c ≤ 6.5%, HOMA-IR ≤ 4.6, C-peptide > 2.72 ng/mL, and BMI ≤ 40 kg/m2 predicted complete remission. The independent predictors of complete remission were age ≤ 45 years, duration of diabetes ≤ 5 years, use of a single oral antidiabetic, HOMA-IR ≤ 4.6, and C-peptide > 2.72 ng/mL. A combined marker of young age, short duration of DM, and low HOMA-IR predicted complete remission with sensitivity 93% and specificity 82%. Independent predictors of complete remission of T2DM after LSG were younger age, shorter duration, single oral antidiabetic, lower HOMA-IR, and higher C-peptide.
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Affiliation(s)
| | | | - Mohamed A Marie
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Ahmed Rabiee
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mona Youssry Helmy
- Internal Medicine Department, Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Mohamed Sabry Tourky
- Department of Surgery, Great Western Hospitals NHS Foundation Trust, Swindon, UK
| | - Mohamed Gamal Qassem
- Department of General Surgery, Faculty of Medicine, Ain Shams University, Cairo, Egypt
| | - Hossam El-Din Shaaban
- Gastroenterology Department, National Hepatology and Tropical Medicine Research Institute, Cairo, Egypt
| | - Mohamed D Sarhan
- General Surgery Department, Faculty of Medicine, Cairo University, Cairo, Egypt
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Steenackers N, Vanuytsel T, Augustijns P, Tack J, Mertens A, Lannoo M, Van der Schueren B, Matthys C. Adaptations in gastrointestinal physiology after sleeve gastrectomy and Roux-en-Y gastric bypass. Lancet Gastroenterol Hepatol 2021; 6:225-237. [PMID: 33581761 DOI: 10.1016/s2468-1253(20)30302-2] [Citation(s) in RCA: 66] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/10/2020] [Revised: 07/27/2020] [Accepted: 07/29/2020] [Indexed: 01/19/2023]
Abstract
Linked to the growing obesity epidemic, demand for bariatric and metabolic surgery has increased, the most common procedures being sleeve gastrectomy and Roux-en-Y gastric bypass. Originally, bariatric procedures were described as purely restrictive, malabsorptive, or combined restrictive-malabsorptive procedures limiting food intake, nutrient absorption, or both. Nowadays, anatomical alterations are known to affect gastrointestinal physiology, which in turn affects the digestion and absorption of nutrients and drugs. Therefore, understanding gastrointestinal physiology is crucial to prevent postoperative nutritional deficiencies and to optimise postoperative drug therapy. Preclinical and clinical research indicates that sleeve gastrectomy accelerates liquid and solid gastric emptying and small intestinal transit, and increases bile acid serum levels, whereas its effects on gastrointestinal acidity, gastric and pancreatic secretions, surface area, and colonic transit remain largely unknown. Roux-en-Y gastric bypass diminishes gastric acid secretion, accelerates liquid gastric emptying, and increases bile acid serum levels, but its effects on intestinal pH, solid gastric emptying, intestinal transit time, gastric enzyme secretions, and surface area remain largely unknown. In this Review, we summarise current knowledge of the effects of these two procedures on gastrointestinal physiology and assess the knowledge gaps.
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Affiliation(s)
- Nele Steenackers
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
| | - Tim Vanuytsel
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Patrick Augustijns
- Department of Chronic Diseases and Metabolism, and Drug Delivery and Disposition, Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium
| | - Jan Tack
- Translational Research Center for Gastrointestinal Disorders, KU Leuven, Leuven, Belgium
| | - Ann Mertens
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
| | - Matthias Lannoo
- Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium
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Do Gut Hormones Contribute to Weight Loss and Glycaemic Outcomes after Bariatric Surgery? Nutrients 2021; 13:nu13030762. [PMID: 33652862 PMCID: PMC7996890 DOI: 10.3390/nu13030762] [Citation(s) in RCA: 38] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2020] [Revised: 02/18/2021] [Accepted: 02/20/2021] [Indexed: 02/07/2023] Open
Abstract
Bariatric surgery is an effective intervention for management of obesity through treating dysregulated appetite and achieving long-term weight loss maintenance. Moreover, significant changes in glucose homeostasis are observed after bariatric surgery including, in some cases, type 2 diabetes remission from the early postoperative period and postprandial hypoglycaemia. Levels of a number of gut hormones are dramatically increased from the early period after Roux-en-Y gastric bypass and sleeve gastrectomy—the two most commonly performed bariatric procedures—and they have been suggested as important mediators of the observed changes in eating behaviour and glucose homeostasis postoperatively. In this review, we summarise the current evidence from human studies on the alterations of gut hormones after bariatric surgery and their impact on clinical outcomes postoperatively. Studies which assess the role of gut hormones after bariatric surgery on food intake, hunger, satiety and glucose homeostasis through octreotide use (a non-specific inhibitor of gut hormone secretion) as well as with exendin 9–39 (a specific glucagon-like peptide-1 receptor antagonist) are reviewed. The potential use of gut hormones as biomarkers of successful outcomes of bariatric surgery is also evaluated.
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Shen H, Ding L, Baig M, Tian J, Wang Y, Huang W. Improving glucose and lipids metabolism: drug development based on bile acid related targets. Cell Stress 2021; 5:1-18. [PMID: 33447732 PMCID: PMC7784708 DOI: 10.15698/cst2021.01.239] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Bariatric surgery is one of the most effective treatment options for severe obesity and its comorbidities. However, it is a major surgery that poses several side effects and risks which impede its clinical use. Therefore, it is urgent to develop alternative safer pharmacological approaches to mimic bariatric surgery. Recent studies suggest that bile acids are key players in mediating the metabolic benefits of bariatric surgery. Bile acids can function as signaling molecules by targeting bile acid nuclear receptors and membrane receptors, like FXR and TGR5 respectively. In addition, the composition of bile acids is regulated by either the hepatic sterol enzymes such as CYP8B1 or the gut microbiome. These bile acid related targets all play important roles in regulating metabolism. Drug development based on these targets could provide new hope for patients without the risks of surgery and at a lower cost. In this review, we summarize the most updated progress on bile acid related targets and development of small molecules as drug candidates based on these targets.
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Affiliation(s)
- Hanchen Shen
- School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Lili Ding
- Shanghai Key Laboratory of Complex Prescriptions and MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.,Department of Diabetes Complications and Metabolism, Institute of Diabetes and Metabolism Research Center, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA
| | - Mehdi Baig
- Department of Diabetes Complications and Metabolism, Institute of Diabetes and Metabolism Research Center, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA
| | - Jingyan Tian
- Shanghai Institute of Endocrine and Metabolic Diseases, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China
| | - Yang Wang
- School of Pharmacy, Fudan University, Shanghai 201203, China
| | - Wendong Huang
- Department of Diabetes Complications and Metabolism, Institute of Diabetes and Metabolism Research Center, Beckman Research Institute, City of Hope National Medical Center, 1500 E. Duarte Road, Duarte, CA 91010, USA
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Jonsson I, Bojsen-Møller KN, Kristiansen VB, Veedfald S, Wewer Albrechtsen NJ, Clausen TR, Kuhre RE, Rehfeld JF, Holst JJ, Madsbad S, Svane MS. Effects of Manipulating Circulating Bile Acid Concentrations on Postprandial GLP-1 Secretion and Glucose Metabolism After Roux-en-Y Gastric Bypass. Front Endocrinol (Lausanne) 2021; 12:681116. [PMID: 34084153 PMCID: PMC8166580 DOI: 10.3389/fendo.2021.681116] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 04/16/2021] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Altered bile acid (BA) turnover has been suggested to be involved in the improved glucose regulation after Roux-en-Y gastric bypass (RYGB), possibly via stimulation of GLP-1 secretion. We investigated the role of exogenous as well as endogenous BAs for GLP-1 secretion after RYGB by administering chenodeoxycholic acid (CDCA) and the BA sequestrant colesevelam (COL) both in the presence and the absence of a meal stimulus. METHODS Two single-blinded randomized cross-over studies were performed. In study 1, eight RYGB operated participants ingested 200 ml water with 1) CDCA 1.25 g or 2) CDCA 1.25 g + colesevelam 3.75 g on separate days. In study 2, twelve RYGB participants ingested on separate days a mixed meal with addition of 1) CDCA 1.25 g, 2) COL 3.75 g or 3) COL 3.75 g × 2, or 4) no additions. RESULTS In study 1, oral intake of CDCA increased circulating BAs, GLP-1, C-peptide, glucagon, and neurotensin. Addition of colesevelam reduced all responses. In study 2, addition of CDCA enhanced meal-induced increases in plasma GLP-1, glucagon and FGF-19 and lowered plasma glucose and C-peptide concentrations, while adding colesevelam lowered circulating BAs but did not affect meal-induced changes in plasma glucose or measured gastrointestinal hormones. CONCLUSION In RYGB-operated persons, exogenous CDCA enhanced meal-stimulated GLP-1 and glucagon secretion but not insulin secretion, while the BA sequestrant colesevelam decreased CDCA-stimulated GLP-1 secretion but did not affect meal-stimulated GLP-1, C-peptide or glucagon secretion, or glucose tolerance. These findings suggest a limited role for endogenous bile acids in the acute regulation of postprandial gut hormone secretion or glucose metabolism after RYGB.
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Affiliation(s)
- Isabella Jonsson
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
| | - Kirstine N. Bojsen-Møller
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | | | - Simon Veedfald
- Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nicolai J. Wewer Albrechtsen
- Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Clinical Biochemistry Rigshospitalet, Copenhagen, Denmark
- Novo Nordisk Foundation Center for Protein Research, University of Copenhagen, Copenhagen, Denmark
| | | | - Rune E. Kuhre
- Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- Research and Development, Novo Nordisk A/S, Måløv, Denmark
| | - Jens F. Rehfeld
- Department of Clinical Biochemistry Rigshospitalet, Copenhagen, Denmark
| | - Jens J. Holst
- Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Sten Madsbad
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- *Correspondence: Sten Madsbad, ; Maria S. Svane,
| | - Maria S. Svane
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
- Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark
- Department of Surgical Gastroenterology, Hvidovre Hospital, Hvidovre, Denmark
- *Correspondence: Sten Madsbad, ; Maria S. Svane,
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Mak TK, Huang S, Guan B, Au H, Chong TH, Peng J, Chen F, Liang C, Lai W, Ho L, Wang C, Yang J. Bile acid, glucose, lipid profile, and liver enzyme changes in prediabetic patients 1 year after sleeve gastrectomy. BMC Surg 2020; 20:329. [PMID: 33317506 PMCID: PMC7737260 DOI: 10.1186/s12893-020-00998-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2020] [Accepted: 12/02/2020] [Indexed: 12/14/2022] Open
Abstract
BACKGROUND Few articles have studied individuals with prediabetes after sleeve gastrectomy. Bile acid and lipid levels remain inconsistent in postbariatric patients. The purpose of this study was to explore bile acid, glucose, lipid, and liver enzyme changes in patients with different diabetes statuses who underwent sleeve gastrectomy. The impact of bariatric surgery and its potential benefits for prediabetic patients was also discussed. METHODS A total of 202 overweight and obese patients who underwent bariatric surgery in our hospital between January 2016 and October 2018 were retrospectively reviewed. Patients were divided into prediabetes (n = 32), nondiabetes (n = 144), and diabetes (n = 26) groups and analysed. Glucose and lipid data were collected from medical records at baseline and at each follow-up visit. RESULT Significant improvements in body weight, glucose and lipid levels, and liver enzymes (P ≤ 0.05) in prediabetic patients were found throughout the first year postoperatively. Improvement in glycaemic control was first seen one month postoperatively, followed by persistent improvement in the next 12 months. Total bile acid (TBA) decreased, which was associated with ALT improvement in prediabetic patients 1-year post-surgery. There were no significant differences in HbA1c, glucose, or triglycerides (TGs) between prediabetic and T2DM patients or between prediabetic and nondiabetic patients at 12 months post-surgery. CONCLUSION LSG is highly effective at interfering with glucose and lipid levels as well as total bile acid levels in prediabetic patients in the first year postoperatively. Thus, LSG is indeed an alternative for overweight and obese prediabetic patients.
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Affiliation(s)
- Tsz Kin Mak
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630 China
| | - Shifang Huang
- Department of Intensive Care Unit, First Affiliated Hospital of Jinan University, Guangzhou, 510630 China
| | - Bingsheng Guan
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630 China
| | - Hoyin Au
- International School, Jinan University, Guangzhou, 510630 China
| | - Tsz Hong Chong
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630 China
| | - Juzheng Peng
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630 China
| | - Fazhi Chen
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630 China
| | - Chuqiao Liang
- International School, Jinan University, Guangzhou, 510630 China
| | - Wanjing Lai
- International School, Jinan University, Guangzhou, 510630 China
| | - LongLam Ho
- International School, Jinan University, Guangzhou, 510630 China
| | - Cunchuan Wang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630 China
| | - Jingge Yang
- Department of Gastrointestinal Surgery, First Affiliated Hospital of Jinan University, Guangzhou, 510630 China
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Yao J, Kovalik JP, Lai OF, Lee PC, Eng AKH, Chan WH, Lim EKW, Bee YM, Tan HC. Effects of laparoscopic sleeve gastrectomy on concentration and composition of bile acids in an Asian population with morbid obesity. PROCEEDINGS OF SINGAPORE HEALTHCARE 2020. [DOI: 10.1177/2010105820952489] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Background: Bile acids (BAs) are traditionally associated with lipid absorption and phase II detoxification by forming various BA conjugates. Recently, it has been discovered that BAs also regulate glucose metabolism, and the increase in BAs in patients following bariatric surgery may contribute to the post-surgery improvement in insulin resistance (IR). However, while Roux-en-Y gastric bypass can increase BA concentrations post-surgery, this may not be the case after laparoscopic sleeve gastrectomy (LSG). We hypothesized that the profiling of BAs that include the conjugated BA species could detect post-surgery BA changes after LSG. To test our hypothesis, we performed comprehensive profiling of BAs in Asian individuals with morbid obesity at baseline, and at 6 months following LSG. Methods: Fourteen subjects scheduled for LSG were recruited. Anthropometric measurements, oral glucose tolerance test, and biochemistry tests were performed at baseline and at 6 months after LSG. BAs were profiled using liquid chromatography–mass spectrometry. Results: At 6 months, subjects lost significant weight from 117.4±5.4 to 92.1±3.8 kg and demonstrated significant improvement in IR. HOMA-IR decreased from 6.2±0.7 to 2.0±0.2 and the Matsuda index increased from 1.9±0.3 to 3.3±0.3. We did not detect any significant post-operative change in the levels of total BAs (5237.1±1219.4 vs. 3631.7±457.9, p=0.181) or non-sulfated BAs after LSG. However, sulfated BA species increased significantly after LSG. Conclusion: Our study showed that the serum concentrations of sulfated BA species in morbidly obese Asian individuals increased significantly 6 months after LSG; the increase in sulfated BAs after LSG might contribute to the post-surgery improvement of metabolic health.
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Affiliation(s)
- Jie Yao
- Department of General Medicine, Changi General Hospital, Singapore
| | - Jean-Paul Kovalik
- Cardiovascular Metabolic Program, Duke-NUS Medical School, Singapore
| | - Oi Fah Lai
- Department of Clinical Research, Singapore General Hospital, Singapore
| | - Phong Ching Lee
- Department of Endocrinology, Singapore General Hospital, Singapore
| | - Alvin Kim Hock Eng
- Department of Upper Gastrointestinal and Bariatric Surgery, Singapore General Hospital, Singapore
| | - Weng Hoong Chan
- Department of Upper Gastrointestinal and Bariatric Surgery, Singapore General Hospital, Singapore
| | - Eugene Kee Wee Lim
- Department of Upper Gastrointestinal and Bariatric Surgery, Singapore General Hospital, Singapore
| | - Yong Mong Bee
- Department of Endocrinology, Singapore General Hospital, Singapore
| | - Hong Chang Tan
- Department of Endocrinology, Singapore General Hospital, Singapore
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Holter MM, Chirikjian MK, Govani VN, Cummings BP. TGR5 Signaling in Hepatic Metabolic Health. Nutrients 2020; 12:nu12092598. [PMID: 32859104 PMCID: PMC7551395 DOI: 10.3390/nu12092598] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2020] [Revised: 08/20/2020] [Accepted: 08/21/2020] [Indexed: 12/12/2022] Open
Abstract
TGR5 is a G protein-coupled bile acid receptor that is increasingly recognized as a key regulator of glucose homeostasis. While the role of TGR5 signaling in immune cells, adipocytes and enteroendocrine L cells in metabolic regulation has been well described and extensively reviewed, the impact of TGR5-mediated effects on hepatic physiology and pathophysiology in metabolic regulation has received less attention. Recent studies suggest that TGR5 signaling contributes to improvements in hepatic insulin signaling and decreased hepatic inflammation, as well as metabolically beneficial improvements in bile acid profile. Additionally, TGR5 signaling has been associated with reduced hepatic steatosis and liver fibrosis, and improved liver function. Despite the beneficial effects of TGR5 signaling on metabolic health, TGR5-mediated gallstone formation and gallbladder filling complicate therapeutic targeting of TGR5 signaling. To this end, there is a growing need to identify cell type-specific effects of hepatic TGR5 signaling to begin to identify and target the downstream effectors of TGR5 signaling. Herein, we describe and integrate recent advances in our understanding of the impact of TGR5 signaling on liver physiology and how its effects on the liver integrate more broadly with whole body glucose regulation.
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Abstract
PURPOSE OF REVIEW The prevalence of pediatric obesity and its associated complications is increasing around the world. Treatment of obesity is challenging and metabolic and bariatric surgery (MBS) is currently the most effective treatment for this condition. At this time, vertical sleeve gastrectomy (VSG) is the most commonly performed bariatric procedure in adolescents. However, knowledge regarding the efficacy, safety, and durability of VSG in adolescents is still evolving. This review summarizes the most recent updates in the field of MBS particularly VSG in adolescents. RECENT FINDINGS MBS is recommended to treat moderate to severe obesity, especially when complicated by comorbidities. The use of VSG for weight loss is increasing among adolescents and produces similar weight loss at five years in both adolescents and adults. The physiologic mechanisms causing weight loss after VSG are multifactorial and still being investigated. The complication rate after VSG ranges between 0 and 17.5%. SUMMARY VSG appears to be a well-tolerated and effective procedure in adolescents. However, it continues to be underutilized despite the increasing prevalence of moderate to severe obesity in adolescents. It is thus important to educate providers regarding its benefits and safety profile.
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Affiliation(s)
- Vibha Singhal
- Pediatric Endocrinology, Massachusetts General Hospital for Children
- Neuroendocrine Unit, Massachusetts General Hospital
- MGH Weight Center
| | | | - Madhusmita Misra
- Pediatric Endocrinology, Massachusetts General Hospital for Children
- Neuroendocrine Unit, Massachusetts General Hospital
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Keinicke H, Sun G, Mentzel CMJ, Fredholm M, John LM, Andersen B, Raun K, Kjaergaard M. FGF21 regulates hepatic metabolic pathways to improve steatosis and inflammation. Endocr Connect 2020; 9:755-768. [PMID: 32688339 PMCID: PMC7424338 DOI: 10.1530/ec-20-0152] [Citation(s) in RCA: 55] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2020] [Accepted: 07/19/2020] [Indexed: 12/11/2022]
Abstract
The prevalence of non-alcoholic fatty liver disease (NAFLD) has increased dramatically worldwide and, subsequently, also the risk of developing non-alcoholic steatohepatitis (NASH), hepatic fibrosis, cirrhosis and cancer. Today, weight loss is the only available treatment, but administration of fibroblast growth factor 21 (FGF21) analogues have, in addition to weight loss, shown improvements on liver metabolic health but the mechanisms behind are not entirely clear. The aim of this study was to investigate the hepatic metabolic profile in response to FGF21 treatment. Diet-induced obese (DIO) mice were treated with s.c. administration of FGF21 or subjected to caloric restriction by switching from high fat diet (HFD) to chow to induce 20% weight loss and changes were compared to vehicle dosed DIO mice. Cumulative caloric intake was reduced by chow, while no differences were observed between FGF21 and vehicle dosed mice. The body weight loss in both treatment groups was associated with reduced body fat mass and hepatic triglycerides (TG), while hepatic cholesterol was slightly decreased by chow. Liver glycogen was decreased by FGF21 and increased by chow. The hepatic gene expression profiles suggest that FGF21 increased uptake of fatty acids and lipoproteins, channeled TGs toward the production of cholesterol and bile acid, reduced lipogenesis and increased hepatic glucose output. Furthermore, FGF21 appeared to reduce inflammation and regulate hepatic leptin receptor-a expression. In conclusion, FGF21 affected several metabolic pathways to reduce hepatic steatosis and improve hepatic health and markedly more genes than diet restriction (61 vs 16 out of 89 investigated genes).
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Affiliation(s)
- Helle Keinicke
- Insulin and Device Trial Operations, Novo Nordisk A/S, Søborg, Denmark
| | - Gao Sun
- Pharmacology and Histopathology, Novo Nordisk A/S, China
| | - Caroline M Junker Mentzel
- Department of Experimental Animal Models, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
| | - Merete Fredholm
- Department of Veterinary Clinical and Animal Science, Faculty of Health and Medical Sciences, University of Copenhagen, Frederiksberg C, Denmark
| | - Linu Mary John
- Global Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, Denmark
| | - Birgitte Andersen
- Global Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, Denmark
| | - Kirsten Raun
- Global Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, Denmark
| | - Marina Kjaergaard
- Global Obesity and Liver Disease Research, Novo Nordisk A/S, Måløv, Denmark
- Correspondence should be addressed to M Kjaergaard:
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45
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So SSY, Yeung CHC, Schooling CM, El-Nezami H. Targeting bile acid metabolism in obesity reduction: A systematic review and meta-analysis. Obes Rev 2020; 21:e13017. [PMID: 32187830 DOI: 10.1111/obr.13017] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2019] [Revised: 02/16/2020] [Accepted: 02/20/2020] [Indexed: 02/06/2023]
Abstract
A systematic review and meta-analysis was conducted of studies that address the association of bile acid (BA) with obesity and of studies on the effects of treatment in patients with obesity on BA metabolism, assessed from systemic BA, fibroblast growth factor 19 (FGF19), 7α-hydroxy-4-cholesten-3-one (C4) level, and faecal BA. We searched PubMed, Embase, and the Cochrane Library from inception to 1 August 2019 using the keywords obesity, obese, body mass index, and overweight with bile acid, FGF19, FXR, and TGR5. Two reviewers independently searched, selected, and assessed the quality of studies. Data were analysed using either fixed or random effect models with inverse variance weighting. Of 3771 articles, 33 papers were relevant for the association of BA with obesity of which 22 were included in the meta-analysis, and 50 papers were relevant for the effect of obesity interventions on BA of which 20 were included in the meta-analysis. Circulating fasting total BA was not associated with obesity. FGF19 was inversely and faecal BA excretion was positively associated with obesity. Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) modulated BA metabolism, ie, increased BA and FGF19. Our results indicate that BA metabolism is altered in obesity. Certain bariatric surgeries including RYGB and SG modulate BA, whether these underlie the beneficial effect of the treatment should be investigated.
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Affiliation(s)
- Stephanie Sik Yu So
- School of Biological Sciences, Faculty of Science, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam, Hong Kong
| | - Chris Ho Ching Yeung
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong
| | - C Mary Schooling
- School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong.,Graduate School of Public Health and Health Policy, City University of New York, New York, United States
| | - Hani El-Nezami
- School of Biological Sciences, Faculty of Science, Kadoorie Biological Sciences Building, The University of Hong Kong, Pokfulam, Hong Kong.,Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
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Serum Bile Acid Levels Before and After Sleeve Gastrectomy and Their Correlation with Obesity-Related Comorbidities. Obes Surg 2020; 29:2517-2526. [PMID: 31069691 DOI: 10.1007/s11695-019-03877-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS The rising prevalence of morbid obesity is increasing the demand for bariatric surgery. The benefits observed after bariatric surgery seems to be not fully explained by surgery-induced weight loss or traditional cardiovascular risk factors regression or improvement. Some evidences suggest that bile acid (BA) levels change after bariatric surgery, thus suggesting that BA concentrations could influence some of the metabolic improvement induced by bariatric surgery. In this report, we have characterized circulating BA patterns and compared them to metabolic and vascular parameters before and after sleeve gastrectomy (SG). PATIENTS AND METHODS Seventy-nine subjects (27 males, 52 females, aged 45 ± 12 years, mean BMI 45 ± 7 kg/m2) SG candidates were included in the study. Before and about 12 months after SG, all subjects underwent a clinical examination, blood tests (including lipid profile, plasma glucose and insulin, both used for calculating HOMA-IR, and glycated hemoglobin), ultrasound visceral fat area estimation, ultrasound flow-mediated dilation evaluation, and determination of plasma BA concentrations. RESULTS Before SG, both primary and secondary BA levels were higher in insulin-resistant obese subjects than in non-insulin resistant obese, and BA were positively associated with the markers of insulin-resistance. After SG, total (conjugated and unconjugated) cholic acids significantly decreased (p 0.007), and total lithocholic acids significantly increased (p 0.017). SG-induced total cholic and chenodeoxycholic acid changes were directly associated with surgery-induced glycemia (p 0.011 and 0.033 respectively) and HOMA-IR (p 0.016 and 0.012 respectively) changes. CONCLUSIONS Serum BA are associated with glucose metabolism and particularly with markers of insulin-resistance. SG modifies circulating BA pool size and composition. SG-induced BA changes are associated with insulin-resistance amelioration. In conclusion, an interplay between glucose metabolism and circulating BA exists but further studies are needed.
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47
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Eiken A, Fuglsang S, Eiken M, Svane MS, Kuhre RE, Wewer Albrechtsen NJ, Hansen SH, Trammell SAJ, Svenningsen JS, Rehfeld JF, Bojsen-Møller KN, Jørgensen NB, Holst JJ, Madsbad S, Madsen JL, Dirksen C. Bilio-enteric flow and plasma concentrations of bile acids after gastric bypass and sleeve gastrectomy. Int J Obes (Lond) 2020; 44:1872-1883. [PMID: 32317753 DOI: 10.1038/s41366-020-0578-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 03/04/2020] [Accepted: 03/27/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND/OBJECTIVES Bile acids in plasma are elevated after bariatric surgery and may contribute to metabolic improvements, but underlying changes in bile flow are poorly understood. We assessed bilio-enteric flow of bile and plasma bile concentrations in individuals with Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG) surgery compared with matched non-surgical controls (CON). SUBJECTS/METHODS Fifteen RYGB, 10 SG and 15 CON underwent 99Tc-mebrofenin cholescintigraphy combined with intake of a high-fat 111In-DTPA-labelled meal and frequent blood sampling. A 75Se-HCAT test was used to assess bile acid retention. RESULTS After RYGB, gallbladder filling was decreased (p = 0.045 versus CON), basal flow of bile into the small intestine increased (p = 0.005), bile acid retention augmented (p = 0.021) and basal bile acid plasma concentrations elevated (p = 0.009). During the meal, foods passed unimpeded through the gastric pouch resulting in almost instant postprandial mixing of bile and foods, but the postprandial rise in plasma bile acids was brief and associated with decreased overall release of fibroblast growth factor-19 (FGF-19) compared with CON (p = 0.033). After SG, bile flow and retention were largely unaltered (p > 0.05 versus CON), but gastric emptying was accelerated (p < 0.001) causing earlier mixture of bile and foods also in this group. Neither basal nor postprandial bile acid concentrations differed between SG and CON. CONCLUSIONS Bilio-enteric bile flow is markedly altered after RYGB resulting in changes in plasma concentrations of bile acids and FGF-19, whereas bile flow and plasma concentrations are largely unaltered after SG.
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Affiliation(s)
- Aleksander Eiken
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
| | - Stefan Fuglsang
- Department of Clinical Physiology and Nuclear Medicine, Centre for Functional Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark
| | - Markus Eiken
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
| | - Maria S Svane
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
| | - Rune E Kuhre
- NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Nicolai J Wewer Albrechtsen
- Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,NNF Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department. of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
| | - Svend H Hansen
- Department. of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
| | - Samuel A J Trammell
- NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens S Svenningsen
- NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Jens F Rehfeld
- Department. of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark
| | | | - Nils B Jørgensen
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
| | - Jens J Holst
- NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.,Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Sten Madsbad
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark
| | - Jan L Madsen
- Department of Clinical Physiology and Nuclear Medicine, Centre for Functional Imaging and Research, Hvidovre Hospital, Hvidovre, Denmark
| | - Carsten Dirksen
- Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark.
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TGR5 Protects Against Colitis in Mice, but Vertical Sleeve Gastrectomy Increases Colitis Severity. Obes Surg 2020; 29:1593-1601. [PMID: 30623320 DOI: 10.1007/s11695-019-03707-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is the most effective long-term treatment for obesity. However, there are conflicting reports on the effect of bariatric surgery on inflammatory bowel disease (IBD). Bariatric surgery increases bile acid concentrations, which can decrease inflammation by signaling through the bile acid receptor, TGR5. TGR5 signaling protects against chemically induced colitis in mice. VSG increases circulating bile acid concentrations to increase TGR5 signaling, which contributes to improved metabolic regulation after VSG. Therefore, we investigated the effect of VSG on chemically induced colitis development and the role of TGR5 in this context. METHODS VSG or sham surgery was performed in high fat diet-fed male Tgr5+/+ and Tgr5-/- littermates. Sham-operated mice were food restricted to match their body weight to VSG-operated mice. Colitis was induced with 2.5% dextran sodium sulfate (DSS) in water post-operatively. Body weight, energy intake, fecal scoring, colon histopathology, colonic markers of inflammation, goblet cell counts, and colonic microRNA-21 levels were assessed. RESULTS VSG decreased body weight independently of genotype. Consistent with previous work, genetic ablation of TGR5 increased the severity of DSS-induced colitis. Notably, despite the effect of VSG to decrease body weight and increase TGR5 signaling, VSG increased the severity of DSS-induced colitis. VSG-induced increases in colitis were associated with increased colonic expression of TNF-α, IL-6, MCP-1, and microRNA-21. CONCLUSIONS While our data demonstrate that TGR5 protects against colitis, they also demonstrate that VSG potentiates chemically induced colitis in mice. These data suggest that individuals undergoing VSG may be at increased risk for developing colitis; however, further study is needed.
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49
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Talavera-Urquijo E, Beisani M, Balibrea JM, Alverdy JC. Is bariatric surgery resolving NAFLD via microbiota-mediated bile acid ratio reversal? A comprehensive review. Surg Obes Relat Dis 2020; 16:1361-1369. [PMID: 32336663 DOI: 10.1016/j.soard.2020.03.013] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/05/2019] [Revised: 01/18/2020] [Accepted: 03/11/2020] [Indexed: 02/07/2023]
Abstract
Despite the fact that there is still insufficient evidence to consider non-alcoholic fatty liver disease (NAFLD) as an stand-alone indication for bariatric surgery, many clinical and histopathological beneficial effects on both NAFLD and non-alcoholic steatohepatitis (NASH) have been shown. Although weight loss seems to be the obvious mechanism, weight-loss independent factors are also believed to be involved. Among them, changes in gut microbiota and bile acids (BA) composition may be playing an unappreciated role in the improvement of NAFLD. In this review we examine the mechanisms and interdependence of the gut microbiota and BA, and their influence on NAFLD pathogenesis and its reversal following bariatric surgery. According to the currently available evidence, gut microbiota has a major influence on BA composition. In fact, both BA and microbiome disturbances (dysbiosis) play a role in the etiopathogenesis of NAFLD and might be potential therapeutic targets. In addition, bariatric surgery can modify the intraluminal ileal environment in a way that causes significant repopulation of the gut microbiota and a reversal of the plasma primary/secondary BA ratio, which, in turn, induces weigh-independent metabolic improvements.
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Affiliation(s)
- Eider Talavera-Urquijo
- Department of General & Digestive Surgery, Vall d'Hebron University Hospital, Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Marc Beisani
- Department of Surgery, Hospital del Mar, Barcelona, Spain
| | - José M Balibrea
- Department of Gastrointestinal Surgery, Hospital Clínic de Barcelona, Universitat de Barcelona, Barcelona, Spain.
| | - John C Alverdy
- Department of Surgery University of Chicago, Pritzker School of Medicine, Chicago, Illinois
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50
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Li K, Zou J, Li S, Guo J, Shi W, Wang B, Han X, Zhang H, Zhang P, Miao Z, Li Y. Farnesoid X receptor contributes to body weight-independent improvements in glycemic control after Roux-en-Y gastric bypass surgery in diet-induced obese mice. Mol Metab 2020; 37:100980. [PMID: 32305491 PMCID: PMC7182762 DOI: 10.1016/j.molmet.2020.100980] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/11/2020] [Revised: 03/12/2020] [Accepted: 03/12/2020] [Indexed: 02/08/2023] Open
Abstract
Objective Roux-en-Y gastric bypass surgery (RYGB) can achieve long-term remission of type 2 diabetes. However, the specific molecular mechanism through which this occurs has remained largely elusive. Bile acid signaling through the nuclear hormone receptor farnesoid X receptor (FXR) exerts beneficial effects after sleeve gastrectomy (VSG), which has similar effects to RYGB. Therefore, we investigated whether FXR signaling is necessary to mediate glycemic control after RYGB. Methods RYGB or sham surgery was performed in high-fat diet-induced obese FXR−/− (knockout) and FXR+/+ (wild type) littermates. Sham-operated mice were fed ad libitum (S-AL) or by weight matching (S-WM) to RYGB mice via caloric restriction. Body weight, body composition, food intake, energy expenditure, glucose tolerance tests, insulin tolerance tests, and homeostatic model assessment of insulin resistance were performed. Results RYGB surgery decreases body weight and fat mass in WT and FXR-KO mice. RYGB surgery has similar effects on food intake and energy expenditure independent of genotype. In addition, body weight-independent improvements in glucose control were attenuated in FXR −/− relative to FXR +/+ mice after RYGB. Furthermore, pharmacologic blockade of the glucagon-like peptide-1 receptor (GLP-1R) blunts the glucoregulatory effects of RYGB in FXR +/+ but not in FXR −/− mice at 4 weeks after surgery. Conclusions These results suggest that FXR signaling is not required for the weight loss up to 16 weeks after RYGB. Although most of the improvements in glucose homeostasis are secondary to RYGB-induced weight loss in wild type mice, FXR signaling contributes to glycemic control after RYGB in a body weight-independent manner, which might be mediated by an FXR-GLP-1 axis during the early postoperative period.
The reduction in body weight after RYGB is independent of FXR, which is mainly due to a decrease in net energy intake. RYGB prevents the weight loss-induced decrease observed in nonsurgical weight-matched mice in both genotypes. FXR signaling contributes to glycemic control after RYGB in a body weight-independent manner. The early body weight-independent improvements in glucose homeostasis after RYGB might be mediated by an FXR-GLP-1 axis.
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Affiliation(s)
- Kun Li
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, PR China
| | - Jianan Zou
- Department of Nephrology, Huadong Hospital Affiliated to Fudan University, Shanghai, 200040, PR China
| | - Song Li
- School of Basic Medicine, Shandong First Medical University, Tai'an, 271000, PR China
| | - Jing Guo
- Discipline Planning Department, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, PR China
| | - Wentao Shi
- Clinical Research Center, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, PR China
| | - Bing Wang
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, PR China
| | - Xiaodong Han
- Department of Metabolic & Bariatric Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China
| | - Hongwei Zhang
- Department of Metabolic & Bariatric Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China
| | - Pin Zhang
- Department of Metabolic & Bariatric Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, PR China
| | - Zengmin Miao
- School of Life Sciences, Shandong First Medical University, Tai'an, 271000, PR China.
| | - Yousheng Li
- Department of General Surgery, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, 200011, PR China.
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