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Chen Y, Du H, Wang X, Li B, Chen X, Yang X, Zhao C, Zhao J. ANGPTL4 May Regulate the Crosstalk Between Intervertebral Disc Degeneration and Type 2 Diabetes Mellitus: A Combined Analysis of Bioinformatics and Rat Models. J Inflamm Res 2023; 16:6361-6384. [PMID: 38161353 PMCID: PMC10757813 DOI: 10.2147/jir.s426439] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Accepted: 12/19/2023] [Indexed: 01/03/2024] Open
Abstract
Introduction The crosstalk between intervertebral disc degeneration (IVDD) and type 2 diabetes mellitus (T2DM) has been investigated. However, the common mechanism underlying this phenomenon has not been clearly elucidated. This study aimed to explore the shared gene signatures of IVDD and T2DM. Methods The expression profiles of IVDD (GSE27494) and T2DM (GSE20966) were acquired from the Gene Expression Omnibus database. Five hub genes including ANGPTL4, CCL2, CCN3, THBS2, and INHBA were preliminarily screened. GO (Gene Ontology) enrichment analysis, functional correlation analysis, immune filtration, Transcription factors (TFs)-mRNA-miRNA coregulatory network, and potential drugs prediction were performed following the identification of hub genes. RNA sequencing, in vivo and in vitro experiments on rats were further performed to validate the expression and function of the target gene. Results Five hub genes (ANGPTL4, CCL2, CCN3, THBS2, and INHBA) were identified. GO analysis demonstrated the regulation of the immune system, extracellular matrix (ECM), and SMAD protein signal transduction. There was a strong correlation between hub genes and different functions, including lipid metabolism, mitochondrial function, and ECM degradation. The immune filtration pattern grouped by disease and the expression of hub genes showed significant changes in the immune cell composition. TFs-mRNA-miRNA co-expression networks were constructed. In addition, pepstatin showed great drug-targeting relevance based on potential drugs prediction of hub genes. ANGPTL4, a gene that mediates the inhibition of lipoprotein lipase activity, was eventually determined after hub gene screening, validation by different datasets, RNA sequencing, and experiments. Discussion This study screened five hub genes and ANGPTL4 was eventually determined as a potential target for the regulation of the crosstalk in patients with IVDD and T2DM.
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Affiliation(s)
- Yan Chen
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Han Du
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Xin Wang
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Baixing Li
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Xuzhuo Chen
- Department of Oral Surgery, Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases, Shanghai Ninth People’s Hospital, College of Stomatology, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Xiao Yang
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Changqing Zhao
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China
| | - Jie Zhao
- Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200011, People’s Republic of China
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Luo X, Tao F, Tan C, Xu CY, Zheng ZH, Pang Q, He XA, Cao JQ, Duan JY. Enhanced glucose homeostasis via Clostridium symbiosum-mediated glucagon-like peptide 1 inhibition of hepatic gluconeogenesis in mid-intestinal bypass surgery. World J Gastroenterol 2023; 29:5471-5482. [PMID: 37900993 PMCID: PMC10600812 DOI: 10.3748/wjg.v29.i39.5471] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2023] [Revised: 09/11/2023] [Accepted: 10/11/2023] [Indexed: 10/19/2023] Open
Abstract
BACKGROUND The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood. AIM To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism. METHODS Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor. RESULTS The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal Lactobacillus, Clostridium symbiosum, Ruminococcus gnavus, and Bilophila. Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota. CONCLUSION The findings of this study demonstrate that the introduction of postoperative intestinal Clostridium symbiosum in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.
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Affiliation(s)
- Xin Luo
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
| | - Fang Tao
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
| | - Cai Tan
- Department of Women’s Health, Jiangxi Maternal and Child Health Hospital, Nanchang 330000, Jiangxi Province, China
| | - Chi-Ying Xu
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
| | - Zhi-Hua Zheng
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
| | - Qiang Pang
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
| | - Xiang-An He
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
| | - Jia-Qing Cao
- Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
| | - Jin-Yuan Duan
- Department of General Surgery, The First Affiliated Hospital of Nanchang University, Nanchang 330000, Jiangxi Province, China
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Valezi AC, Campos ACL, Bahten LCV. BRAZILIAN MULTI-SOCIETY POSITION STATEMENT ON EMERGING BARIATRIC AND METABOLIC SURGICAL PROCEDURES. ARQUIVOS BRASILEIROS DE CIRURGIA DIGESTIVA : ABCD = BRAZILIAN ARCHIVES OF DIGESTIVE SURGERY 2023; 36:e1759. [PMID: 37729276 PMCID: PMC10510373 DOI: 10.1590/0102-672020230041e1759] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/03/2023] [Accepted: 07/13/2023] [Indexed: 09/22/2023]
Abstract
This Brazilian multi-society position statement on emerging bariatric and metabolic surgical procedures was issued by the Brazilian Society of Bariatric and Metabolic Surgery (SBCBM), the Brazilian College of Digestive Surgery (CBCD), and the Brazilian College of Surgeons (CBC). This document is the result of a Brazilian Emerging Surgeries Forum aimed at evaluating the results of surgeries that are not yet listed in the Federal Council of Medicine (CFM), the regulatory agency that oversees and regulates medical practice in Brazil. The Forum integrated more than 400 specialists and academics with extensive knowledge about bariatric and metabolic surgery, representing the three surgical societies: SBCBM, CBC, and CBCD. International speakers participated online and presented their experiences with the techniques under discussion, emphasizing the regulatory policies in their countries. The indications for surgery and the subsequent procedures were carefully reviewed, including one anastomosis gastric bypass (OAGB), single anastomosis duodeno-ileal with sleeve gastrectomy (SADI-S or OADS), sleeve gastrectomy with transit bipartition (SGTB), and sleeve gastrectomy with ileal interposition (SGII). The recommendations of this document are based on an extensive literature review and discussions among bariatric surgery specialists from the three surgical societies. We concluded that patients with a body mass index over 30 kg/m2 may be candidates for metabolic surgery in the presence of comorbidities (arterial hypertension and type 2 diabetes) with no response to clinical treatment of obesity or in the control of other associated diseases. Regarding the surgical procedures, we concluded that OAGB, OADS, and SGTB are associated with low morbidity rates, satisfactory weight loss, and resolution of obesity-related comorbidities such as diabetes and arterial hypertension. SGII was considered a good and viable promising surgical alternative technique. The recommendations of this statement aim to synchronize our societies with the sentiments and understandings of most of our members and also serve as a guide for future decisions regarding bariatric surgical procedures in our country and worldwide.
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Unhapipatpong C, Hiranyatheb P, Phanachet P, Warodomwichit D, Sriphrapradang C, Shantavasinkul PC. Postprandial hypoglycemia after ileocolic interposition and Billroth-II gastrojejunostomy: A case report. Clin Case Rep 2023; 11:e7060. [PMID: 36950668 PMCID: PMC10025248 DOI: 10.1002/ccr3.7060] [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: 11/02/2022] [Revised: 02/03/2023] [Accepted: 02/22/2023] [Indexed: 03/24/2023] Open
Abstract
Postprandial reactive hypoglycemia, or late dumping syndrome, is a common but underrecognized complication from bypass surgery. We report an unusual case of postprandial reactive hypoglycemia in a patient with a severe esophageal stricture from corrosive agent ingestion who underwent ileocolic interposition and an antecolic Billroth-II gastrojejunostomy. A 22-year-old male patient with a one-year history of corrosive ingestion was referred to the hospital for a surgical correction of severe esophageal stricture. After the patient underwent ileocolic interposition and an antecolic Billroth-II gastrojejunostomy, he experienced multiple episodes of gastroesophageal refluxsymptoms during nasogastric feeding and had onset of hypoglycemic symptoms. His plasma glucose level was 59 mg/dL. After we had intraoperatively re-inserted a jejunostomy tube bypassing the ileocolic interposition, and reintroduced enteral nutrition, his hypoglycemic symptoms resolved. We performed a mixed meal tolerance test by nasogastric tube, but the results did not show postprandial hypoglycemia. Although the specific mechanism is unclear, this case suggests gastroesophageal reflux to the ileal interposition may have caused a state of exaggerated hyperinsulinemic response and rebound hypoglycemia. To the best of our knowledge, we are the first to report case of postprandial hypoglycemia after ileocolic interposition, which may have been caused by exaggerated hyperinsulinemic response due to gastroesophageal reflux to the ileal interposition. This syndrome should be considered in the patient who has had ileocolic interposition surgery and has developed postprandial hypoglycemia.
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Affiliation(s)
- Chanita Unhapipatpong
- Department of Medicine, Division of Clinical NutritionKhon Kaen HospitalKhon KaenThailand
| | - Pitichote Hiranyatheb
- Department of Surgery, Division of General Surgery, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Pariya Phanachet
- Department of Medicine, Division of Nutrition and Biochemical Medicine, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Daruneewan Warodomwichit
- Department of Medicine, Division of Nutrition and Biochemical Medicine, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Chutintorn Sriphrapradang
- Department of Medicine, Division of Endocrinology and Metabolism, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
| | - Prapimporn Chattranukulchai Shantavasinkul
- Department of Medicine, Division of Nutrition and Biochemical Medicine, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
- Graduate Program in Nutrition, Faculty of Medicine Ramathibodi HospitalMahidol UniversityBangkokThailand
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Chen W, Zhou S, Xiao J, Liu W, Qu Q, He X. Farnesoid X receptor is inhibited after ileum transposition in diabetic rats: its hypoglycemic effect. Int J Med Sci 2023; 20:595-605. [PMID: 37082732 PMCID: PMC10110471 DOI: 10.7150/ijms.80563] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/06/2022] [Accepted: 03/25/2023] [Indexed: 04/22/2023] Open
Abstract
Background: Aim to investigate bile acid profile changes and the Farnesoid X receptor (FXR) status after ileotransposition (IT), and reveal its possible hypoglycemic mechanism. Methods: Twenty male diabetic rats were randomly assigned into the IT group and the sham IT (SH) group. Bile acid profiles were measured using an ultra-performance liquid chromatography-tandem mass spectrometry. Glucose metabolism was monitored after oral administration of FXR inhibitor and agonist. And the expression of key FXR target genes were measured. Results: The levels of β-muricholic acid (P = 0.047), tauro-α-muricholic acid and tauro-β-muricholic acid (P < 0.001) in plasma in the IT group were higher than those in the SH group, and the levels of taurocholic acid (P = 0.049) and turoursodeoxycholic acid (P = 0.030) were lower than those in the SH group. After inhibition of intestinal FXR, the glucose metabolism in the SH group was improved. When FXR agonist was given, the blood glucose level was increased in both groups. After sacrifice, the levels of glycoursodeoxycholic acid, tauro-α-muricholic acid and tauro-β-muricholic acid in liver and ileum tissues were higher than those in the SH group (P < 0.05), the level of α- muricholic acid (P < 0.001) in liver tissues were lower than that in the SH group. Moreover, the expression of CYP7A1 mRNA (P < 0.001) and FGF15 mRNA (P = 0.001) in the IT group was significantly higher, and the expression of PEPCK mRNA (P = 0.004), SREPB1c mRNA (P = 0.005) and SRB1 mRNA (P = 0.001) were significantly lower than that in the SH group. Conclusions: We demonstrate a remarkable heterogeneity of BA profiles after IT, FXR activation might has a detrimental effect on glucose metabolism.
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Affiliation(s)
| | | | | | | | | | - Xiaodong He
- ✉ Corresponding author: Xiaodong He, Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing 100730, P. R. China Tel: 0086 13521624987; Fax: 0086 01069156002
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Wang AN, Carlos J, Fraser GM, McGuire JJ. Zucker Diabetic Sprague Dawley rat (ZDSD): type 2 diabetes translational research model. Exp Physiol 2022; 107:265-282. [PMID: 35178802 PMCID: PMC9314054 DOI: 10.1113/ep089947] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Accepted: 02/02/2022] [Indexed: 11/30/2022]
Abstract
New Findings
What is the topic of this review? The Zucker Diabetic‐Sprague Dawley (ZDSD) rat is in the early adoption phase of use by researchers in the fields of diabetes, including prediabetes, obesity and metabolic syndrome. It is essential that physiology researchers choose preclinical models that model human type 2 diabetes appropriately and are aware of the limitations on experimental design. What advances does it highlight? Our review of the scientific literature finds that although sex, age and diets contribute to variability, the ZDSD phenotype and disease progression model the characteristics of humans who have prediabetes and diabetes, including co‐morbidities. Abstract Type 2 diabetes (T2D) is a prevalent disease and a significant concern for global population health. For persons with T2D, clinical treatments target not only the characteristics of hyperglycaemia and insulin resistance, but also co‐morbidities, such as obesity, cardiovascular and renal disease, neuropathies and skeletal bone conditions. The Zucker Diabetic‐Sprague Dawley (ZDSD) rat is a rodent model developed for experimental studies of T2D. We reviewed the scientific literature to highlight the characteristics of T2D development and the associated phenotypes, such as metabolic syndrome, cardiovascular complications and bone and skeletal pathologies in ZDSD rats. We found that ZDSD phenotype characteristics are independent of leptin receptor signalling. The ZDSD rat develops prediabetes, then progresses to overt diabetes that is accelerated by introduction of a timed high‐fat diet. In male ZDSD rats, glycated haemoglobin (HbA1c) increases at a constant rate from 7 to >30 weeks of age. Diabetic ZDSD rats are moderately hypertensive compared with other rat strains. Diabetes in ZDSD rats leads to endothelial dysfunction in specific vasculatures, impaired wound healing, decreased systolic and diastolic cardiac function, neuropathy and nephropathy. Changes to bone composition and the skeleton increase the risk of bone fractures. Zucker Diabetic‐Sprague Dawley rats have not yet achieved widespread use by researchers. We highlight sex‐related differences in the ZDSD phenotype and gaps in knowledge for future studies. Overall, scientific data support the premise that the phenotype and disease progression in ZDSD rats models the characteristics in humans. We conclude that ZDSD rats are an advantageous model to advance understanding and discovery of treatments for T2D through preclinical research.
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Affiliation(s)
- Andrea N Wang
- Departments of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
| | - Joselia Carlos
- Departments of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
| | - Graham M Fraser
- Division of Biomedical Sciences, Faculty of Medicine, Memorial University, St. John's, Newfoundland, Canada
| | - John J McGuire
- Departments of Medical Biophysics, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada.,Physiology & Pharmacology, Schulich School of Medicine & Dentistry, Western University, London, Ontario, Canada
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Poloczek J, Tarnawska M, Chełmecka E, Łaszczyca P, Gumprecht J, Stygar D. High Fat, High Sugar Diet and DJOS Bariatric Surgery Influence Plasma Levels of Fetuin-B, Growth Differentiation Factor-15, and Pentraxin 3 in Diet-Induced Obese Sprague-Dawley Rats. Nutrients 2021; 13:nu13103632. [PMID: 34684637 PMCID: PMC8539134 DOI: 10.3390/nu13103632] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Revised: 10/14/2021] [Accepted: 10/15/2021] [Indexed: 01/14/2023] Open
Abstract
The liver plays a central role in glucose and fatty acid metabolism and acts as an endocrine organ that secretes hepatokines with diverse systemic effects. The study aimed to examine the influence of duodenojejunal omega switch (DJOS) bariatric surgery in combination with different diets on glucose administration parameters and hepatokines levels. After 8 weeks on high fat, high sugar diet (HFS) or control diets (CD), Sprague-Dawley rats underwent DJOS or SHAM (control) surgery. For the next 8 weeks after the surgery, half of DJOS and SHAM-operated animals were kept on the same diet as before, and half had a diet change. The oral glucose tolerance test (OGTT) was performed three times: 8 weeks before and 4 and 8 weeks after surgery. Fetuin-B, growth differentiation factor-15 (GDF-15), pentraxin 3 (PTX3) plasma levels were analyzed. DJOS surgery had a beneficial effect on oral glucose tolerance test (OGTT) results and the area under the curve (AUCOGTT). The OGTT results depended on the time elapsed after the surgery, the type of diet used, the surgery performed, and the interaction between these factors. DJOS bariatric surgery reduced fetuin-B and GDF15 plasma levels. Interaction between the type of surgery performed and diet used influenced the fetuin-B and PTX-3 plasma levels. A dietary regime is essential to achieve therapeutic and clinical goals after bariatric surgery.
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Affiliation(s)
- Jakub Poloczek
- Department of Rehabilitation, 3rd Specialist Hospital in Rybnik, Energetyków 46, 44-200 Rybnik, Poland;
- Department of Internal Medicine, Diabetology, and Nephrology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland;
| | - Monika Tarnawska
- Faculty of Natural Sciences, Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Bankowa 9, 40-007 Katowice, Poland; (M.T.); (P.Ł.)
| | - Elżbieta Chełmecka
- Department of Statistics, Department of Instrumental Analysis, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland;
| | - Piotr Łaszczyca
- Faculty of Natural Sciences, Institute of Biology, Biotechnology and Environmental Protection, University of Silesia in Katowice, Bankowa 9, 40-007 Katowice, Poland; (M.T.); (P.Ł.)
| | - Janusz Gumprecht
- Department of Internal Medicine, Diabetology, and Nephrology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland;
| | - Dominika Stygar
- Department of Physiology, Faculty of Medical Sciences in Zabrze, Medical University of Silesia, Poniatowskiego 15, 40-055 Katowice, Poland
- Correspondence: ; Tel.: +48-32-272-23-62
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Ileal transposition helps to regulate plasma hepatokine levels in obese Zucker (Crl:ZUC(ORL)-Lepr fa) rats. Sci Rep 2021; 11:7774. [PMID: 33833309 PMCID: PMC8032747 DOI: 10.1038/s41598-021-87293-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2020] [Accepted: 03/17/2021] [Indexed: 02/01/2023] Open
Abstract
We studied the long-term effect of ileal transposition (IT) metabolic surgery on the hepatokines: retinol-binding protein-4 (RBP4), α-2-HS-glycoprotein (aHSG/fetuin-A), and fibroblast growth factor 21 (FGF21), C-reactive protein (CRP) plasma levels, glucose metabolism, body weight, liver histology, as well as total lipids concentration in muscle, liver, and fat tissue of obese Zucker (Crl:ZUC(ORL)-Leprfa) rats. 14 adult males were randomly submitted either to IT or SHAM (control) surgery. Pre-operative hepatokines plasma levels were not significantly different in rats submitted to IT or SHAM protocol. Three months after the procedures the plasma levels of RBP4, aHSG, FGF21, and CRP were significantly lower in IT-operated animals when compared to SHAM-operated group. Three and 12 weeks after the IT and SHAM surgery, the AUCOGTT were significantly lower than AUCOGTT before the surgery. HOMA-IR was lower in rats after IT surgery in comparison to the SHAM-operated rats. Muscle and liver total lipids concentration was reduced after the IT procedure when compared to pre-IT conditions. IT had a significant reductive impact on the body weight in comparison to SHAM surgery in the 4th, 6th, 8th, and 10th week after the surgery. We conclude that IT reduces hepatokines' plasma concentrations, muscle and liver total lipids concentration but not the inflammatory processes in the liver of Zucker (Crl:ZUC(ORL)-Leprfa) rats.
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Ileal interposition improves metabolic syndrome parameters in a rat model of metabolic syndrome induced by monosodium glutamate. Life Sci 2020; 266:118846. [PMID: 33309719 DOI: 10.1016/j.lfs.2020.118846] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/19/2020] [Revised: 11/24/2020] [Accepted: 11/25/2020] [Indexed: 11/23/2022]
Abstract
AIMS Metabolic syndrome (MetS) is a cluster of metabolic abnormalities. Anatomically restructuring of the gastrointestinal system has recently been an important subject of research in the treatment of MetS and closely related diseases. The aim of this study is to ensure the remission of parameters that define MetS by ileal interposition (IT) and to examine the effect of IT on plasma total GLP-1 and pancreatic GLP-1R expression. MAIN METHODS To induce MetS, newborn male Wistar albino rats were given MSG (4 g/mg) on days 0, 2, 4, 6, 8, and 10. The control group was injected with saline. In the 5th month, IT or sham surgery was performed on the MetS rats. The lipid levels, abdominal obesity, insulin level, OGTT, Lee index, HOMA-IR, plasma GLP-1 and pancreas GLP-1R expression were evaluated 2 months after surgery. KEY FINDINGS The results showed that IT significantly improved hyperinsulinemia (p = 0.013) and lipid profile (TG p = 0.0001; TCHOL p = 0.018; HDL p = 0.001). Furthermore, it normalized the Lee index (p = 0.006) and insulin resistance. The IT did not affect the secretion of the GLP-1, but the expression levels of pancreas GLP-1R were increased (p = 0.006). SIGNIFICANCE IT surgery corrected the MetS parameters in this rat model. The healing effects of IT surgery could be caused by mechanisms in the target tissues of insulin. The decrease in pancreatic GLP-1R levels in the MetS groups might be a compensatory response to the harmful effects of hyperinsulinemia in these groups. These results show that IT can be useful in the treatment of MetS.
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Abstract
BACKGROUND Standardization of the key measurements of a procedure's finished anatomic configuration strengthens surgical practice, research, and patient outcomes. A consensus meeting was organized to define standard versions of 25 bariatric metabolic procedures. METHODS A panel of experts in bariatric metabolic surgery from multiple continents was invited to present technique descriptions and outcomes for 4 classic, or conventional, and 21 variant and emerging procedures. Expert panel and audience discussion was followed by electronic voting on proposed standard dimensions and volumes for each procedure's key anatomic alterations. Consensus was defined as ≥ 70% agreement. RESULTS The Bariatric Metabolic Surgery Standardization World Consensus Meeting (BMSS-WOCOM) was convened March 22-24, 2018, in New Delhi, India. Discussion confirmed heterogeneity in procedure measurements in the literature. A set of anatomic measurements to serve as the standard version of each procedure was proposed. After two voting rounds, 22/25 (88.0%) configurations posed for consideration as procedure standards achieved voting consensus by the expert panel, 1 did not attain consensus, and 2 were not voted on. All configurations were voted on by ≥ 50% of 50 expert panelists. The Consensus Statement was developed from scientific evidence collated from presenters' slides and a separate literature review, meeting video, and transcripts. Review and input was provided by consensus panel members. CONCLUSIONS Standard versions of the finished anatomic configurations of 22 surgical procedures were established by expert consensus. The BMSS process was undertaken as a first step in developing evidence-based standard bariatric metabolic surgical procedures with the aim of improving consistency in surgery, data collection, comparison of procedures, and outcome reporting.
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Yan K, Chen W, Zhu H, Lin G, Sun W, Liu X, Pan H, Wang L, Yang H, Liu M, Gong F. The Changes of Serum Metabolites in Diabetic GK Rats after Ileal Transposition Surgery. Obes Surg 2020; 29:882-890. [PMID: 30397878 DOI: 10.1007/s11695-018-3582-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Ileal transposition (IT) surgery could improve metabolism. Metabolomics has been applied comprehensively in analyzing the global dynamic alterations of metabolites. In the present study, we aimed to investigate serum metabolite alterations in diabetic Goto-Kakizaki (GK) rats after IT surgery. METHODS Male GK rats were subjected to IT and Sham-IT surgery. Six weeks later, body weight, food intake, fat mass, and serum biochemical parameters were measured. The serum metabolomic fingerprint was analyzed using ultra-performance liquid chromatography-mass spectrometry (LC-MS)-based, non-targeted metabolomic approach. The differential metabolites were identified using principal component analysis and orthogonal partial least squares discriminant analysis. Metabolic pathway analysis was performed using HMDB and KEGG databases. RESULTS The body weight, food intake, fat mass, serum levels of glucose and insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) of IT rats were significantly decreased when compared with Sham-IT rats (all P < 0.05). In the metabolomics analysis, ten serum differential metabolites were identified. Compared with Sham-IT rats, serum LysoPC(O-18:0) and PG(20:4/20:0) of IT rats were decreased, while genistein 4'-O-glucuronide, 5,6:8,9-Diepoxyergost-22-ene-3,7beta-diol, PI(16:0/18:2(9Z,12Z)), docosapentaenoic acid, 3-Oxo-4,6-choladienoic acid, 3-Oxocholic acid, and TG were increased. Pathway analysis highlighted the following pathways: ether lipid metabolism, alpha linolenic acid and linolenic acid metabolism, incretin synthesis and secretion, free fatty acid receptors, and biosynthesis of unsaturated fatty acids. CONCLUSIONS IT surgery could significantly decrease body weight and fat mass and improve glucose metabolism in diabetic GK rats. These beneficial effects might be related to the changes of serum metabolites which involved in lipid metabolism, bile acids, and incretin.
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Affiliation(s)
- Kemin Yan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Weijie Chen
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Guole Lin
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Wei Sun
- Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/School of Basic Medicine, Peking Union Medical College, Beijing, 100730, China
| | - Xiaoyan Liu
- Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/School of Basic Medicine, Peking Union Medical College, Beijing, 100730, China
| | - Hui Pan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Linjie Wang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Hongbo Yang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Meijuan Liu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Fengying Gong
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
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12
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Ileal Transposition Increases Pancreatic β Cell Mass and Decreases β Cell Senescence in Diet-Induced Obese Rats. Obes Surg 2020; 30:1849-1858. [DOI: 10.1007/s11695-020-04406-6] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
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13
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Shan CX, Qiu NC, Liu ME, Zha SL, Song X, Du ZP, Rao WS, Jiang DZ, Zhang W, Qiu M. Effects of Diet on Bile Acid Metabolism and Insulin Resistance in Type 2 Diabetic Rats after Roux-en-Y Gastric Bypass. Obes Surg 2019; 28:3044-3053. [PMID: 29721762 DOI: 10.1007/s11695-018-3264-2] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/30/2022]
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) is effective for the treatment of type 2 diabetes mellitus; however, the mechanism remains unclear. METHODS The effects of RYGB on postprandial responses to three different diets (low carbohydrate (CH)-rich diet, high CH-rich diet, and fat-rich diet) of different nutritional composition in a Goto-Kakizaki (GK) diabetic rat model were assessed by measuring glucose tolerance, insulin resistance, incretin responses, and bile acid (BA) metabolism. RESULTS GK-RYGB group rats lost weight and preferred low CH-rich diet, but there were no significant differences in BW among the different diets. Glucose tolerance and insulin resistance were improved in rats who underwent RYGB, together with higher levels of circulating BAs, plasma GLP-1, and PYY levels. GK-RYGB rats fed high CH-rich or fat-rich diet showed increased glucose level and insulin resistance, together with high plasma BA, GIP, and PYY levels compared to those fed a low CH-rich diet. CONCLUSION RYGB improves glucose tolerance and insulin resistance which may be related to BA metabolism and hormone levels, and the nutrient composition of the diet affects the treatment effect of RYGB on T2DM.
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Affiliation(s)
- Cheng-Xiang Shan
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Nian-Cun Qiu
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China.,Department of General Surgery, Hainan Branch of Chinese PLA General Hospital, Sanya, 572000, China
| | - Miao-E Liu
- Key Laboratory of Reproductive Genetics, Women's Hospital, Zhejiang University, Zhejiang, 310000, China
| | - Si-Luo Zha
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Xin Song
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Zhi-Peng Du
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Wen-Sheng Rao
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Dao-Zhen Jiang
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China
| | - Wei Zhang
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China.
| | - Ming Qiu
- Department of General Surgery, Chang Zheng Hospital affiliated to Second Military Medical University, 440 Chengdu North Road, Shanghai, 200003, China.
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14
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Pinte L, Balaban DV, Băicuş C, Jinga M. Non-alcoholic fatty pancreas disease - practices for clinicians. ROMANIAN JOURNAL OF INTERNAL MEDICINE = REVUE ROUMAINE DE MEDECINE INTERNE 2019; 57:209-219. [PMID: 30901317 DOI: 10.2478/rjim-2019-0005] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/30/2018] [Indexed: 02/07/2023]
Abstract
Obesity is a growing health burden worldwide, increasing the risk for several diseases featuring the metabolic syndrome - type 2 diabetes mellitus, dyslipidemia, non-alcoholic fatty liver disease and cardiovascular diseases. With the increasing epidemic of obesity, a new pathologic condition has emerged as a component of the metabolic syndrome - that of non-alcoholic fatty pancreas disease (NAFPD). Similar to non-alcoholic fatty liver disease (NAFLD), NAFPD comprises a wide spectrum of disease - from deposition of fat in the pancreas - fatty pancreas, to pancreatic inflammation and possibly pancreatic fibrosis. In contrast with NAFLD, diagnostic evaluation of NAFPD is less standardized, consisting mostly in imaging methods. Also the natural evolution of NAFPD and its association with pancreatic cancer is much less studied. Not least, the clinical consequences of NAFPD remain largely presumptions and knowledge about its metabolic impact is limited. This review will cover epidemiology, pathogenesis, diagnostic evaluation tools and treatment options for NAFPD, with focus on practices for clinicians.
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Affiliation(s)
- Larisa Pinte
- "Colentina" Clinical Hospital, Bucharest, Romania
| | - Daniel Vasile Balaban
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- "Dr. Carol Davila" Central Military Emergency University Hospital, Bucharest, Romania
| | - Cristian Băicuş
- "Colentina" Clinical Hospital, Bucharest, Romania
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
| | - Mariana Jinga
- "Carol Davila" University of Medicine and Pharmacy, Bucharest, Romania
- "Dr. Carol Davila" Central Military Emergency University Hospital, Bucharest, Romania
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15
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Hung C, Napoli E, Ross-Inta C, Graham J, Flores-Torres AL, Stanhope KL, Froment P, Havel PJ, Giulivi C. Ileal interposition surgery targets the hepatic TGF-β pathway, influencing gluconeogenesis and mitochondrial bioenergetics in the UCD-T2DM rat model of diabetes. FASEB J 2019; 33:11270-11283. [PMID: 31307210 DOI: 10.1096/fj.201802714r] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Ileal interposition (IT) is a surgical procedure that increases the delivery of incompletely digested nutrients and biliary and pancreatic secretions to the distal intestinal mucosa. Here, we investigated the metabolic impact of this intervention in 2-mo-old prediabetic University of California, Davis type 2 diabetes mellitus rats by assessing liver gene expression at 1.5 mo post-IT surgery. Pathway analysis indicated decreased signaling via TGF-β/Smad (a family of proteins named mothers against decapentaplegic homologs), peroxisome proliferator-activated receptor (PPAR), and PI3K-Akt-AMPK-mechanistic target of rapamycin, likely targeting hepatic stellate cells because differentiation and activation of these cells is associated with decreased signaling via PPAR and TGF-β/Smad. IT surgery up-regulated the expression of genes involved in regulation of cholesterol and terpenoid syntheses and down-regulated those involved in glycerophospholipid metabolism [including cardiolipin (CL)], lipogenesis, and gluconeogenesis. Consistent with the down-regulation of the hepatic CL pathway, IT surgery produced a metabolic switch in liver, kidney cortex, and fat depots toward decreased mitochondrial fatty acid β-oxidation, the process required to fuel high energy-demanding pathways (e.g., gluconeogenesis and glyceroneogenesis), whereas opposite effects were observed in skeletal and cardiac muscles. This study demonstrates for the first time the presence of metabolic pathways that complement the effects of IT surgery to maximize its benefits and potentially identify similarly effective, durable, and less invasive therapeutic options for metabolic disease, including inhibitors of TGF-β signaling.-Hung, C., Napoli, E., Ross-Inta, C., Graham, J., Flores-Torres, A. L., Stanhope, K. L., Froment, P., Havel, P. J., Giulivi, C. Ileal interposition surgery targets the hepatic TGF-β pathway, influencing gluconeogenesis and mitochondrial bioenergetics in the UCD-T2DM rat model of diabetes.
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Affiliation(s)
- Connie Hung
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA
| | - Eleonora Napoli
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA
| | - Catherine Ross-Inta
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA
| | - James Graham
- Department of Nutrition, University of California, Davis, Davis, California, USA
| | - Amanda L Flores-Torres
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.,Department of Biochemistry, Medical Sciences Campus, University of Puerto Rico, San Juan, Puerto Rico
| | - Kimber L Stanhope
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.,Department of Nutrition, University of California, Davis, Davis, California, USA
| | - Pascal Froment
- Unité de Physiologie de la Reproduction et des Comportements, Institut National de la Recherche Agronomique, Unité Mixte de Recherche (UMR) 85, Paris, France
| | - Peter J Havel
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.,Department of Nutrition, University of California, Davis, Davis, California, USA
| | - Cecilia Giulivi
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, California, USA.,Medical Investigations of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis, Davis, California, USA
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16
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Cheng Z, Liu G, Zhang X, Bi D, Hu S. Improvement of Glucose Metabolism Following Long-Term Taurocholic Acid Gavage in a Diabetic Rat Model. Med Sci Monit 2018; 24:7206-7212. [PMID: 30298865 PMCID: PMC6192455 DOI: 10.12659/msm.912429] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022] Open
Abstract
BACKGROUND Bile acids (BAs) are signaling molecules that participate in maintaining glucose homeostasis. Acute enteral infusion of BAs potently reduces the glycemic response to glucose, associated with an increase of incretin hormones. However, the effect of long-term supplementation of BAs on glucose metabolism has not been fully investigated. MATERIAL AND METHODS Thirty diabetic rats were assigned to a control group (n=10), a low TCA group (L-TCA group, n=10), and a high TCA group (H-TCA group, n=10). Rats in the control group were fed a regular high-fat diet (HFD), while rats in the L-TCA group and H-TCA group were fed a TCA (taurocholic acid)-mixed HFD with the concentrations of 0.05% and 0.3%, respectively, to control the intake of HFD and TCA. Energy intake, body weight, serum insulin, glucose tolerance, insulin sensitivity, GLP-1, and total serum BAs were measured at week 2 and week 12. RESULTS At week 2 there were no significant differences in body weight, daily energy intake, glucose tolerance, serum insulin, insulin sensitivity, GLP-1, or fasting total serum BAs between the 3 groups. At week 12, fasting blood glucose and intragastric glucose tolerance were better in the H-TCA group, with significantly greater insulin and GLP-1 secretion and better insulin sensitivity; no significant differences in body weight, energy intake, or total fasting serum BAs were observed. CONCLUSIONS Long-term supplementation with small doses of TCA was demonstrated to improve glucose metabolism in a diabetic rat model and may be a potential target for diabetes control.
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Affiliation(s)
- Zhiqiang Cheng
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland)
| | - Guozhi Liu
- Department of Neonatology, Weifang Yidu Central Hospital, Qingzhou, Shandong, China (mainland)
| | - Xiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland)
| | - Dongsong Bi
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland)
| | - Sanyuan Hu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China (mainland)
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17
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Foschi D, Sorrentino L, Tubazio I, Vecchio C, Vago T, Bevilacqua M, Rizzi A, Corsi F. Ileal interposition coupled with duodenal diverted sleeve gastrectomy versus standard medical treatment in type 2 diabetes mellitus obese patients: long-term results of a case-control study. Surg Endosc 2018; 33:1553-1563. [PMID: 30225603 DOI: 10.1007/s00464-018-6443-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2018] [Accepted: 09/05/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND Randomized controlled trials have demonstrated that bariatric surgery is effective in obtaining remission of type 2 diabetes mellitus (T2DM) in obese patients, yet no data exist in the literature from prospective studies with ileal interposition with duodenal diversion sleeve gastrectomy (II-DD-SG). The aim of this case-control study is to investigate if II-DD-SG is superior to medical treatment in T2DM obese patients. METHODS Thirty obese patients (BMI > 30) affected by T2DM were recruited for surgery (II-DD-SG) between 2008 and 2011 and were matched with an equal control group which received standard medical treatment. Anthropometric measures, glucose metabolism, cardiovascular risk factors were determined baseline and during follow-up. The primary end point was T2DM remission; reduction of body weight, BMI, and cardiovascular risk factors were secondary end-points. RESULTS Shortly after II-DD-SG, normalization of glucose plasma levels and glycated hemoglobin was observed followed by a significant decrease in body weight and BMI. At one-year follow-up, insulin resistance strongly declined as did insulin plasma levels. Complete remission was observed in 26 patients (86%); 2 (6.6%) had partial remission, and two (6.6%) were still diabetic. After 5 years, 17 of 25 patients on follow-up (68%) showed complete remission of T2DM and 56% had remission of cardiovascular risk factors. Only two patients receiving medical treatment showed complete remission of T2DM (p < 0.0001 versus II-DD-SG). No significant changes of anthropometric parameters and lipid metabolism were recorded. CONCLUSIONS II-DD-SG is an effective surgical procedure, able to induce complete and prolonged remission of T2DM in obese patients as opposed to medical treatment.
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Affiliation(s)
- Diego Foschi
- Chair of General Surgery, Department of Biomedical and Clinical Sciences "Luigi Sacco", L. Sacco Hospital, University of Milan, via G. B. Grassi 74, 20157, Milan, Italy.
| | - Luca Sorrentino
- Chair of General Surgery, Department of Biomedical and Clinical Sciences "Luigi Sacco", L. Sacco Hospital, University of Milan, via G. B. Grassi 74, 20157, Milan, Italy
| | - Igor Tubazio
- Chair of General Surgery, Department of Biomedical and Clinical Sciences "Luigi Sacco", L. Sacco Hospital, University of Milan, via G. B. Grassi 74, 20157, Milan, Italy
| | - Consuelo Vecchio
- Unit of Dietetics, Department of Medicine, Luigi Sacco Hospital, via G. B. Grassi 74, 20157, Milan, Italy
| | - Tarcisio Vago
- Endocrine Laboratory Unit, Department of Medicine, Luigi Sacco Hospital, via G. B. Grassi 74, 20157, Milan, Italy
| | - Maurizio Bevilacqua
- Unit of Endocrinology, Department of Medicine, Luigi Sacco Hospital, via G. B. Grassi 74, 20157, Milan, Italy
| | - Andrea Rizzi
- Chair of General Surgery, Department of Biomedical and Clinical Sciences "Luigi Sacco", L. Sacco Hospital, University of Milan, via G. B. Grassi 74, 20157, Milan, Italy
| | - Fabio Corsi
- Chair of General Surgery, Department of Biomedical and Clinical Sciences "Luigi Sacco", L. Sacco Hospital, University of Milan, via G. B. Grassi 74, 20157, Milan, Italy
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18
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Garibay D, Lou J, Lee SA, Zaborska KE, Weissman MH, Sloma E, Donahue L, Miller AD, White AC, Michael MD, Sloop KW, Cummings BP. β Cell GLP-1R Signaling Alters α Cell Proglucagon Processing after Vertical Sleeve Gastrectomy in Mice. Cell Rep 2018; 23:967-973. [PMID: 29694904 PMCID: PMC5983903 DOI: 10.1016/j.celrep.2018.03.120] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/17/2017] [Revised: 03/05/2018] [Accepted: 03/27/2018] [Indexed: 12/11/2022] Open
Abstract
Bariatric surgery, such as vertical sleeve gastrectomy (VSG), causes high rates of type 2 diabetes remission and remarkable increases in postprandial glucagon-like peptide-1 (GLP-1) secretion. GLP-1 plays a critical role in islet function by potentiating glucose-stimulated insulin secretion; however, the mechanisms remain incompletely defined. Therefore, we applied a murine VSG model to an inducible β cell-specific GLP-1 receptor (GLP-1R) knockout mouse model to investigate the role of the β cell GLP-1R in islet function. Our data show that loss of β cell GLP-1R signaling decreases α cell GLP-1 expression after VSG. Furthermore, we find a β cell GLP-1R-dependent increase in α cell expression of the prohormone convertase required for the production of GLP-1 after VSG. Together, the findings herein reveal two concepts. First, our data support a paracrine role for α cell-derived GLP-1 in the metabolic benefits observed after VSG. Second, we have identified a role for the β cell GLP-1R as a regulator of α cell proglucagon processing.
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Affiliation(s)
- Darline Garibay
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Jon Lou
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Seon A Lee
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Karolina E Zaborska
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Margot H Weissman
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Erica Sloma
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Leanne Donahue
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Andrew D Miller
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - Andrew C White
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA
| | - M Dodson Michael
- Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
| | - Kyle W Sloop
- Diabetes and Complications, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN 46285, USA
| | - Bethany P Cummings
- Department of Biomedical Sciences, Cornell University, Ithaca, NY 14853, USA.
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19
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Yan K, Chen W, Zhu H, Lin G, Pan H, Li N, Wang L, Yang H, Liu M, Gong F. Ileal Transposition Surgery Decreases Fat Mass and Improves Glucose Metabolism in Diabetic GK Rats: Possible Involvement of FGF21. Front Physiol 2018; 9:191. [PMID: 29593555 PMCID: PMC5854974 DOI: 10.3389/fphys.2018.00191] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2017] [Accepted: 02/23/2018] [Indexed: 12/14/2022] Open
Abstract
Objective: Ileal transposition (IT) surgery has been reported to improve glucose and lipid metabolism, and fibroblast growth factor 21 (FGF21) is a powerful metabolic regulator. In the present study, we aimed to investigate the effects of IT surgery on metabolism and its possible relationship with the FGF21 signaling pathway in diabetic Goto-Kakizaki (GK) rats. Methods: Ten-week-old male GK rats were subjected to IT surgery with translocation of a 10 cm ileal segment to the proximal jejunum (IT group) or sham surgery without the ileum transposition (Sham-IT group). Rats in the no surgery group did not receive any surgical intervention. Six weeks later, body weight, fat mass, fasting blood glucose (FBG), and serum levels of FGF21 and leptin were measured. The expression of the FGF21 signaling pathway and white adipose tissue (WAT) browning-related genes in the WAT and liver were evaluated by real-time reverse transcription polymerase chain reaction (RT-qPCR) and western blot. Results: IT surgery significantly decreased the body weights and FBG levels and increased the insulin sensitivity of GK rats. The total WAT mass of the IT rats showed a 41.5% reduction compared with the Sham-IT rats, and serum levels of FGF21 and leptin of the IT rats decreased by 26.3 and 61.7%, respectively (all P < 0.05). The mRNA levels of fibroblast growth factor receptor 1 (FGFR1) and its co-receptor β klotho (KLB) in the perirenal WAT (pWAT) of the IT rats were 1.4- and 2.4-fold that of the Sham-IT rats, respectively, and the FGFR1 protein levels were 1.7-fold of the Sham-IT rats (all P < 0.05). In accordance with the pWAT, the protein levels of FGFR1 and KLB in the epididymal WAT (eWAT) of the IT rats notably increased to 3.0- and 3.9-fold of the Sham-IT rats (P < 0.05). Furthermore, uncoupling protein 1 (UCP1) protein levels in the eWAT and pWAT of the IT rats also increased to 2.2- and 2.3-fold of the Sham-IT rats (P < 0.05). However, the protein levels of FGFR1 and KLB in the subcutaneous WAT (sWAT) of the IT rats decreased by 34.4 and 72.1%, respectively, compared with the Sham-IT rats (P < 0.05). In addition, the protein levels of FGF21 and KLB in the livers of IT rats were 3.9- and 2.3-fold of the Sham-IT rats (all P < 0.05). Conclusions: IT surgery significantly decreased fat mass and improved glucose metabolism in diabetic GK rats. These beneficial roles of IT surgery were probably associated with its stimulatory action on the expression of FGFR1 and KLB in both the eWAT and the pWAT, thereby promoting UCP1 expression in these tissues.
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Affiliation(s)
- Kemin Yan
- Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Weijie Chen
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Guole Lin
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Hui Pan
- Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Naishi Li
- Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Linjie Wang
- Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Hongbo Yang
- Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Meijuan Liu
- Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
| | - Fengying Gong
- Key Laboratory of Endocrinology of National Health and Family Planning Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, China
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20
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Kleinert M, Clemmensen C, Hofmann SM, Moore MC, Renner S, Woods SC, Huypens P, Beckers J, de Angelis MH, Schürmann A, Bakhti M, Klingenspor M, Heiman M, Cherrington AD, Ristow M, Lickert H, Wolf E, Havel PJ, Müller TD, Tschöp MH. Animal models of obesity and diabetes mellitus. Nat Rev Endocrinol 2018; 14:140-162. [PMID: 29348476 DOI: 10.1038/nrendo.2017.161] [Citation(s) in RCA: 555] [Impact Index Per Article: 79.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models.
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Affiliation(s)
- Maximilian Kleinert
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, D-80333 Munich, Germany
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, DK-2200 Copenhagen, Denmark
| | - Christoffer Clemmensen
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, D-80333 Munich, Germany
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
| | - Susanna M Hofmann
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Institute for Diabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Medizinische Klinik und Poliklinik IV, Klinikum der Ludwig-Maximilians-Universität München, Ziemssenstr. 1, D-80336 Munich, Germany
| | - Mary C Moore
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA
| | - Simone Renner
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Chair for Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilan University München, Feodor-Lynen-Str. 25, D-81377 Munich, Germany
| | - Stephen C Woods
- University of Cincinnati College of Medicine, Department of Psychiatry and Behavioral Neuroscience, Metabolic Diseases Institute, 2170 East Galbraith Road, Cincinnati, Ohio 45237, USA
| | - Peter Huypens
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
| | - Johannes Beckers
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Technische Universität München, Chair of Experimental Genetics, D-85354 Freising, Germany
| | - Martin Hrabe de Angelis
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Technische Universität München, Chair of Experimental Genetics, D-85354 Freising, Germany
| | - Annette Schürmann
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), Arthur-Scheunert-Allee 114-116, D-14558 Nuthetal, Germany
| | - Mostafa Bakhti
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Institute for Diabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Institute of Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
| | - Martin Klingenspor
- Chair of Molecular Nutritional Medicine, Technische Universität München, TUM School of Life Sciences Weihenstephan, Gregor-Mendel-Str. 2, D-85354 Freising, Germany
- Else Kröner-Fresenius Center for Nutritional Medicine, Technische Universität München, D-85354 Freising, Germany
- Institute for Food & Health, Technische Universität München, D-85354 Freising, Germany
| | - Mark Heiman
- MicroBiome Therapeutics, 1316 Jefferson Ave, New Orleans, Louisiana 70115, USA
| | - Alan D Cherrington
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37212, USA
| | - Michael Ristow
- Energy Metabolism Laboratory, Institute of Translational Medicine, Swiss Federal Institute of Technology (ETH) Zurich, CH-8603 Zurich-Schwerzenbach, Switzerland
| | - Heiko Lickert
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Institute for Diabetes and Regeneration Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Institute of Stem Cell Research, Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
| | - Eckhard Wolf
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Chair for Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilan University München, Feodor-Lynen-Str. 25, D-81377 Munich, Germany
| | - Peter J Havel
- Department of Molecular Biosciences, School of Veterinary Medicine and Department of Nutrition, 3135 Meyer Hall, University of California, Davis, California 95616-5270, USA
| | - Timo D Müller
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, D-80333 Munich, Germany
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
| | - Matthias H Tschöp
- Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum München, German Research Center for Environmental Health (GmbH), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
- Division of Metabolic Diseases, Department of Medicine, Technische Universität München, D-80333 Munich, Germany
- German Center for Diabetes Research (DZD), Ingolstädter Landstr. 1, D-85764 Neuherberg, Germany
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Adipose depot-specific effects of ileal interposition surgery in UCD-T2D rats: unexpected implications for obesity and diabetes. Biochem J 2018; 475:649-662. [PMID: 29321243 DOI: 10.1042/bcj20170899] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 01/02/2018] [Accepted: 01/07/2018] [Indexed: 12/25/2022]
Abstract
Ileal interposition (IT) surgery delays the onset of diabetes in a rat model of type-2 diabetes (UCD-T2DM). Here, to gain a deeper understanding of the molecular events underlying the effects of IT surgery, we examined the changes in the proteome of four white adipose depots (retroperitoneal, mesenteric, inguinal, and epididymal) and plasma-free fatty acid profile in pre-diabetic rats 1.5 months following IT or sham surgery. The IT-mediated changes were exerted mainly in mesenteric fat and spanned from delayed adipocyte maturation to a neuroendocrine remodeling. Conversely, inguinal, retroperitoneal, and epididymal depots showed opposite trends consistent with increased adipocyte maturation and adipogenesis development prior to overt signs of diabetes, probably orchestrated by peroxisome proliferator-activated receptor gamma signaling and higher plasma n-6/n-3 free fatty acid ratios. The resulting scenario suggests a targeted use of surgical strategies that seek to delay or improve diabetes in order to manipulate adipose depot-specific responses to maximize the duration and beneficial effects of the surgery.
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Ileal Transposition Decreases Plasma Lipopolysaccharide Levels in Association with Increased L Cell Secretion in Non-obese Non-diabetic Rats. Obes Surg 2018; 26:1287-95. [PMID: 26334758 DOI: 10.1007/s11695-015-1879-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Chronic exposure to lipopolysaccharide (LPS) contributes to metabolic abnormalities, but there has been no study to evaluate plasma LPS levels after ileal transposition (IT). We examined the effect of IT on gut hormone secretion and plasma LPS levels and their correlation with metabolic parameters. METHODS Sprague-Dawley rats underwent either IT or sham operation. After 4 weeks, oral glucose tolerance tests (OGTT) were performed and fasting plasma LPS and gut histology were analyzed. RESULTS Compared with the sham group, food intake and body weight decreased, and insulin sensitivity increased in the IT group. During the OGTTs, glucagon, glucagon-like peptide-1 (GLP-1), GLP-2, and peptide YY (PYY) were significantly higher in the IT group than the sham group. The villi length, muscle thickness, and the density of GLP-1 and glucose-dependent insulinotropic polypeptide co-expressing cells (K/L-cells) increased in the transposed ileum compared with the ileum of the sham group. Fasting plasma LPS levels were lower in the IT group than the sham group (5.6 ± 0.2 vs. 6.8 ± 0.1 EU/ml, P = 0.002) and significantly correlated with insulin resistance (r = 0.755, P < 0.001). Plasma LPS levels were negatively correlated with PYY secretion (r = -0.710, P = 0.001), and GLP-2 secretion (r = -0.561, P = 0.019). CONCLUSIONS IT surgery decreased plasma LPS levels in a non-obese non-diabetic rat model, which was associated with improved insulin sensitivity and increased L-cell secretion.
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Albaugh VL, Banan B, Ajouz H, Abumrad NN, Flynn CR. Bile acids and bariatric surgery. Mol Aspects Med 2017; 56:75-89. [PMID: 28390813 PMCID: PMC5603298 DOI: 10.1016/j.mam.2017.04.001] [Citation(s) in RCA: 95] [Impact Index Per Article: 11.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2016] [Revised: 02/27/2017] [Accepted: 04/04/2017] [Indexed: 12/12/2022]
Abstract
Bariatric surgery, specifically Roux-en-Y gastric bypass (RYGB) and vertical sleeve gastrectomy (VSG), are the most effective and durable treatments for morbid obesity and potentially a viable treatment for type 2 diabetes (T2D). The resolution rate of T2D following these procedures is between 40 and 80% and far surpasses that achieved by medical management alone. The molecular basis for this improvement is not entirely understood, but has been attributed in part to the altered enterohepatic circulation of bile acids. In this review we highlight how bile acids potentially contribute to improved lipid and glucose homeostasis, insulin sensitivity and energy expenditure after these procedures. The impact of altered bile acid levels in enterohepatic circulation is also associated with changes in gut microflora, which may further contribute to some of these beneficial effects. We highlight the beneficial effects of experimental surgical procedures in rodents that alter bile secretory flow without gastric restriction or altering nutrient flow. This information suggests a role for bile acids beyond dietary fat emulsification in altering whole body glucose and lipid metabolism strongly, and also suggests emerging roles for the activation of the bile acid receptors farnesoid x receptor (FXR) and G-protein coupled bile acid receptor (TGR5) in these improvements. The limitations of rodent studies and the current state of our understanding is reviewed and the potential effects of bile acids mediating the short- and long-term metabolic improvements after bariatric surgery is critically examined.
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MESH Headings
- Animals
- Bile Acids and Salts/metabolism
- Diabetes Mellitus, Type 2/metabolism
- Diabetes Mellitus, Type 2/microbiology
- Diabetes Mellitus, Type 2/pathology
- Diabetes Mellitus, Type 2/surgery
- Enterohepatic Circulation
- Gastrectomy
- Gastric Bypass
- Gastrointestinal Microbiome/physiology
- Gene Expression Regulation
- Glucose/metabolism
- Homeostasis/physiology
- Humans
- Insulin Resistance
- Obesity, Morbid/metabolism
- Obesity, Morbid/microbiology
- Obesity, Morbid/pathology
- Obesity, Morbid/surgery
- Receptors, Cytoplasmic and Nuclear/genetics
- Receptors, Cytoplasmic and Nuclear/metabolism
- Receptors, G-Protein-Coupled/genetics
- Receptors, G-Protein-Coupled/metabolism
- Rodentia
- Signal Transduction
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Affiliation(s)
- Vance L Albaugh
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Babak Banan
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Hana Ajouz
- American University of Beirut, Beirut, Lebanon
| | - Naji N Abumrad
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA
| | - Charles R Flynn
- Department of Surgery, Vanderbilt University Medical Center, Nashville, TN 37232, USA.
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24
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Liu T, Zhong MW, Liu Y, Sun D, Wei M, Huang X, Cheng YG, Wu QZ, Wu D, Zhang XQ, Wang KX, Hu SY, Liu SZ. Diabetes recurrence after metabolic surgeries correlates with re-impaired insulin sensitivity rather than beta-cell function. World J Gastroenterol 2017; 23:3468-3479. [PMID: 28596682 PMCID: PMC5442082 DOI: 10.3748/wjg.v23.i19.3468] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/20/2017] [Revised: 04/25/2017] [Accepted: 05/04/2017] [Indexed: 02/06/2023] Open
Abstract
AIM To investigate factors causing diabetes recurrence after sleeve gastrectomy (SG) and duodenal-jejunal bypass (DJB).
METHODS SG and DJB were performed on rats with diabetes induced by high-fat diet (HFD) and streptozotocin (STZ). HFD was used to induce diabetes recurrence at 4 wk postoperatively. Body weight, oral glucose tolerance test, homeostatic model assessment of insulin resistance (HOMA-IR), insulin signaling [IR, insulin receptor substrate (IRS)1, IRS2, phosphatidylinositol 3-kinase and AKT in liver and skeletal muscle], oral glucose stimulated insulin secretion, beta-cell morphology (mass, apoptosis and insulin secretion), glucagon-like peptide (GLP)-1, PYY and ghrelin were compared among SG rats with common low-fat diet (SG-LFD), SG with HFD (SG-HFD), DJB rats with LFD (DJB-LFD), DJB with HFD (DJB-HFD) and sham-operation with LFD (Sham) at targeted postoperative times.
RESULTS SG and DJB resulted in significant improvement in glucose tolerance, lower HOMA-IR, up-regulated hepatic and muscular insulin signaling, higher levels of oral glucose-stimulated insulin secretion, bigger beta-cell mass, higher immunofluorescence intensity of insulin, fewer transferase-mediated dUTP-biotin 3’ nick end-labeling (TUNEL)-positive beta cells and higher postprandial GLP-1 and PYY levels than in the Sham group. The improvement in glucose tolerance was reversed at 12 wk postoperatively. Compared with the SG-LFD and DJB-LFD groups, the SG-HFD and DJB-HFD groups showed higher HOMA-IR, down-regulated hepatic and muscular insulin signaling, and more TUNEL-positive beta cells. No significant difference was detected between HFD and LFD groups for body weight, glucose-stimulated insulin secretion, beta-cell mass, immunofluorescence intensity of insulin, and postprandial GLP-1 and PYY levels. Fasting serum ghrelin decreased in SG groups, and there was no difference between HFD-SG and LFD-SG groups.
CONCLUSION HFD reverses the improvement in glucose homeostasis after SG and DJB. Diabetes recurrence may correlate with re-impaired insulin sensitivity, but not with alterations of beta-cell function and body weight.
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Frikke-Schmidt H, O'Rourke RW, Lumeng CN, Sandoval DA, Seeley RJ. Does bariatric surgery improve adipose tissue function? Obes Rev 2016; 17:795-809. [PMID: 27272117 PMCID: PMC5328428 DOI: 10.1111/obr.12429] [Citation(s) in RCA: 83] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2016] [Revised: 03/25/2016] [Accepted: 04/20/2016] [Indexed: 12/19/2022]
Abstract
Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.
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Affiliation(s)
| | - R W O'Rourke
- Department of Surgery, University of Michigan, Ann Arbor, USA
| | - C N Lumeng
- Department of Pediatrics, University of Michigan, Ann Arbor, USA
| | - D A Sandoval
- Department of Surgery, University of Michigan, Ann Arbor, USA
| | - R J Seeley
- Department of Surgery, University of Michigan, Ann Arbor, USA
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Abstract
Obesity and its associated medical conditions continue to increase and add significant burden to patients, as well as health-care systems, worldwide. Bariatric surgery is the most effective treatment for severe obesity and its comorbidities, and resolution of diabetes is weight loss-independent in the case of some operations. Although these weight-independent effects are frequently described clinically, the mechanisms behind them are not well understood and remain an intense area of focus in the growing field of metabolic and bariatric surgery. Perceptions of the mechanisms responsible for the beneficial metabolic effects of metabolic/bariatric operations have shifted from being mostly restrictive and malabsorption over the last 10 to 15 years to being more neuro-hormonal in origin. In this review, we describe recent basic and clinical findings of the major clinical procedures (adjustable gastric banding, vertical sleeve gastrectomy, Roux-en-Y gastric bypass, and biliopancreatic diversion) as well as other experimental procedures (ileal interposition and bile diversion) that recapitulate many of the metabolic effects of these complex operations in a simpler fashion. As the role of bile acids and the gut microbiome on metabolism is becoming increasingly well described, their potential roles in these improvements following metabolic surgery are becoming better appreciated. Bile acid and gut microbiome changes, in light of recent developments, are discussed in the context of these surgical procedures, as well as their implications for future study.
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Affiliation(s)
- Vance L Albaugh
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA
| | - C Robb Flynn
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA
| | - Robyn A Tamboli
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA
| | - Naji N Abumrad
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee, 37232, USA
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Yan M, Song MM, Bai RX, Cheng S, Yan WM. Effect of Roux-en-Y gastric bypass surgery on intestinal Akkermansia muciniphila. World J Gastrointest Surg 2016; 8:301-307. [PMID: 27152136 PMCID: PMC4840169 DOI: 10.4240/wjgs.v8.i4.301] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Revised: 01/11/2016] [Accepted: 01/31/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To investigated changes in intestinal Akkermansia muciniphila (A. muciniphila) and explored the mechanism underlying the therapeutic effects of Roux-en-Y gastric bypass (RYGB) surgery on type 2 diabetes in diabetic Goto-Kakizaki (GK) rats.
METHODS: Male diabetic GK rats (n = 12) aged 8 wk were randomly assigned to the surgery group (GK-RYGB) or sham surgery group (GK-Sham) (n = 6 per group), and another 6 male Wistar rats aged 8 wk served as controls (WS-Sham). In the surgery group, RYGB surgery was conducted, and a sham operation was performed in both sham groups. Fasting blood glucose (FBG) levels before and after surgery, fasting levels of serum insulin and serum glucagon-like peptide-1 (GLP-1) and levels 30 min after intragastric injection of glucose, and the amount of A. muciniphila in the stool were determined. Insulin and GLP-1 were measured by enzyme-linked immunosorbent assay, and A. muciniphila were detected by fluorescence-based quantitative polymerase chain reaction.
RESULTS: The FBG was improved, and serum GLP-1 and insulin increased significantly (P < 0.05) in the GK-RYGB group after surgery compared to levels before surgery and to levels in the GK-Sham group. Before surgery, the amounts of A. muciniphila in the GK-RYGB and GK-Sham groups were significantly lower than in the WS-Sham group (P < 0.05). After surgery, the amount of A. muciniphila in the GK-RYGB group increased markedly compared to that before surgery and to that in the GK-Sham and WS-Sham groups (P < 0.05). In addition, the A. muciniphila amount was positively related to GLP-1 (r = 0.86, P < 0.05).
CONCLUSION: Our results demonstrated RYGB surgery may increase GLP-1 secretion, elevate serum insulin after intragastric injection of glucose, and improve insulin resistance in diabetic GK rats, thereby contributing to a significant reduction in blood glucose. The increased amount of A. muciniphila after RYGB surgery may be related to elevated GLP-1 secretion.
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Oh TJ, Ahn CH, Cho YM. Contribution of the distal small intestine to metabolic improvement after bariatric/metabolic surgery: Lessons from ileal transposition surgery. J Diabetes Investig 2016; 7 Suppl 1:94-101. [PMID: 27186363 PMCID: PMC4854512 DOI: 10.1111/jdi.12444] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/20/2015] [Accepted: 11/11/2015] [Indexed: 12/19/2022] Open
Abstract
Roux-en Y gastric bypass is a highly effective bariatric/metabolic surgical procedure that can induce robust weight loss and even remission of type 2 diabetes. One of the characteristic consequences of Roux-en Y gastric bypass is the expedited nutrient delivery to the distal small intestine, where L-cells are abundant and bile acid reabsorption occurs. To examine the role of the distal small intestine in isolation from other components of Roux-en Y gastric bypass, the ileal transposition (IT) surgery has been used in various rat models. IT relocates the distal ileal segment to the upper jejunum distal to the ligament of Treitz without any other alterations in the gastrointestinal anatomy. Therefore, IT exposes the distal ileal tissue to ingested nutrients after a meal faster than the normal condition. Although there is some inconsistency in the effect of IT according to different types of rat models and different types of surgical protocols, IT typically improved glucose tolerance, increased insulin sensitivity and induced weight loss, and the findings were more prominent in obese diabetic rats. Suggested mechanisms for the metabolic improvements after IT include increased L-cell secretion (e.g., glucagon-like peptides and peptide YY), altered bile acid metabolism, altered host-microbial interaction, attenuated metabolic endotoxemia and many others. Based on the effect of IT, we can conclude that the contribution of the distal small intestine to the metabolic benefits of bariatric/metabolic surgery is quite considerable. By unveiling the mechanism of action of IT, we might revolutionize the treatment for obesity and type 2 diabetes.
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Affiliation(s)
- Tae Jung Oh
- Department of Internal MedicineSeoul National University Bundang HospitalSeongnamKorea; Department of Internal MedicineSeoul National University College of MedicineSeoulKorea
| | - Chang Ho Ahn
- Department of Internal Medicine Seoul National University College of Medicine Seoul Korea
| | - Young Min Cho
- Department of Internal Medicine Seoul National University College of Medicine Seoul Korea
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Oh TJ. In Vivo Models for Incretin Research: From the Intestine to the Whole Body. Endocrinol Metab (Seoul) 2016; 31:45-51. [PMID: 26996422 PMCID: PMC4803560 DOI: 10.3803/enm.2016.31.1.45] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/15/2016] [Revised: 02/11/2016] [Accepted: 02/18/2016] [Indexed: 12/12/2022] Open
Abstract
Incretin hormones are produced by enteroendocrine cells (EECs) in the intestine in response to ingested nutrient stimuli. The incretin effect is defined as the difference in the insulin secretory response between the oral glucose tolerance test and an isoglycemic intravenous glucose infusion study. The pathophysiology of the decreased incretin effect has been studied as decreased incretin sensitivity and/or β-cell dysfunction per se. Interestingly, robust increases in endogenous incretin secretion have been observed in many types of metabolic/bariatric surgery. Therefore, metabolic/bariatric surgery has been extensively studied for incretin physiology, not only the hormones themselves but also alterations in EECs distribution and genetic expression levels of gut hormones. These efforts have given us an enormous understanding of incretin biology from synthesis to in vivo behavior. Further innovative studies are needed to determine the mechanisms and targets of incretin hormones.
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Affiliation(s)
- Tae Jung Oh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea.
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30
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Wang Y, Zhang X, Liu T, Zhong M, Wan H, Liu S, Zhang G, Kassab GS, Hu S. Jejunum-ileum circuit procedure improves glucose metabolism in diabetic rats independent of weight loss. Obesity (Silver Spring) 2016; 24:342-51. [PMID: 26709012 DOI: 10.1002/oby.21339] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/15/2015] [Revised: 07/15/2015] [Accepted: 08/22/2015] [Indexed: 12/25/2022]
Abstract
OBJECTIVE To introduce a lower-risk novel surgical procedure to achieve diabetes reversal along with associated hormonal changes. METHODS Diabetic rats were randomly assigned to jejunum-ileum circuit (JIC), sham-JIC, ileal interposition (IT), and sham-IT groups. The JIC group included two subgroups: short (JIC-S) and long (JIC-L), based on the length between anastomosis and Treitz ligament (LAT ). The body weight, food intake, blood glucose, glucose and insulin tolerance, and gut hormones were measured. The liver gene expression of glucose transporter 2 (GLUT2) and protein expression of glucose-6-phosphatase (G6P) and phosphoenolpyruvate carboxykinase (PKC) were also measured. Following a dye infusion, nutrient delivery was measured at termination day. RESULTS Compared to sham-JIC group, JIC-S group did not reduce body weight or food intake but significantly improved glucose tolerance and insulin resistance. With fast chyme transit, JIC-S not only promoted the secretion of insulin, glucagon-like peptide 1, and peptide YY and decreased leptin, but also upregulated hepatic GLUT2 and downregulated hepatic G6P and PKC. JIC-L group, however, failed to achieve remission of diabetes. CONCLUSION JIC-S relieves diabetes independent of weight loss, as it promotes the secretion of anti-diabetic hormones and inhibits hepatic glucose production. The prolonging of LAT , however, diminishes the hypoglycemic effect.
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Affiliation(s)
- Yanmin Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. Correspondence: Sanyuan Hu
| | - Xiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. Correspondence: Sanyuan Hu
| | - Teng Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. Correspondence: Sanyuan Hu
| | - Mingwei Zhong
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. Correspondence: Sanyuan Hu
| | - Houmin Wan
- Department of General Surgery, the Fourth Hospital of Jinan, Jinan, Shandong, China
| | - Shaozhuang Liu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. Correspondence: Sanyuan Hu
| | - Guangyong Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. Correspondence: Sanyuan Hu
| | - Ghassan S Kassab
- Department of Bioengineering, California Medical Innovations Institute, San Diego, California, USA
| | - Sanyuan Hu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, Shandong, China. Correspondence: Sanyuan Hu
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Amelioration of glycemic control by sleeve gastrectomy and gastric bypass in a lean animal model of type 2 diabetes: restoration of gut hormone profile. Obes Surg 2015; 25:7-18. [PMID: 24902653 DOI: 10.1007/s11695-014-1309-8] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
BACKGROUND In obese diabetic patients, bariatric surgery has been shown to induce remission of type 2 diabetes. Along with weight loss itself, changes in gut hormone profiles after surgery play an important role in the amelioration of glycemic control. However, the potential of gastrointestinal surgery regarding diabetes remission in non-severely obese diabetic patients has yet to be defined. In the present experimental study, we explored the effect of established bariatric procedures with and without duodenal exclusion on glycemic control and gut hormone profile in a lean animal model of type 2 diabetes. METHODS Forty 12- to 14-week-old non-obese diabetic Goto-Kakizaki (GK) rats were randomly assigned to four groups: control group (GKC), sham surgery (GKSS), sleeve gastrectomy (GKSG), and gastric bypass (GKGB). Age-matched Wistar rats served as a non-diabetic control group (WIC). Glycemic control and plasma lipids were assessed at the beginning of the observation period and 4 weeks after surgery. Fasting and mixed meal-induced plasma levels of ghrelin, glucagon-like peptide-17-36 (GLP-1), and peptide tyrosine-tyrosine (PYY) were measured. RESULTS In GK rats, glycemic control improved after sleeve gastrectomy (SG) and gastric bypass (GB). Mixed meal-induced gut hormone profiles in Wistar rats (WIC) were significantly different from those of sham-operated or control group GK rats. After SG and GB, GK rats showed a similar postprandial decrease in ghrelin as observed in non-diabetic WIC. Following both surgical procedures, a significant meal-induced increase in PYY and GLP-1 could be demonstrated. CONCLUSIONS SG and GB induce a similar improvement in overall glycemic control in lean diabetic rodents. Meal-induced profiles of ghrelin, GLP-1, and PYY in GK rats are significantly modified by SG and GB and become similar to those of non-diabetic Wistar rats. Our data do not support the hypothesis that duodenal exclusion and early contact of food with the ileal mucosa alone explain changes in gut hormone profile in GK rats after gastrointestinal surgery.
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Zhang X, Liu T, Wang Y, Zhong M, Zhang G, Liu S, Wu T, Rayner CK, Hu S. Comparative Effects of Bile Diversion and Duodenal-Jejunal Bypass on Glucose and Lipid Metabolism in Male Diabetic Rats. Obes Surg 2015; 26:1565-75. [PMID: 26464241 DOI: 10.1007/s11695-015-1925-y] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Duodenal-jejunal bypass surgery suppresses hepatic de novo lipogenesis and alleviates liver fat accumulation in a diabetic rat model. Obes Surg 2015; 24:2152-60. [PMID: 24898720 DOI: 10.1007/s11695-014-1308-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND Duodenal-jejunal bypass (DJB) surgery can induce rapid and durable remission of type 2 diabetes mellitus (T2DM), but the intrinsic mechanisms remain to be elucidated. Recent studies indicated that improved hepatic insulin resistance and insulin signaling transduction might contribute to the diabetic control after DJB. Given the important role of liver adiposity in hepatic insulin resistance, this study was aimed at investigating the effects of DJB on glucose homeostasis and liver fat accumulation in a T2DM rat model induced by high-fat diet (HFD) and small dose of streptozotocin (STZ). METHODS Forty adult male diabetic rats induced by HFD and small dose of STZ were randomly assigned to sham and DJB groups. Body weight, calorie intake, hormone levels, glucose, and lipid parameters were measured at indicated time points. Subsequently, hepatic triglycerides (TG) content and the protein levels of sterol regulatory element binding protein-1 (SREBP-1), carbohydrate response element binding protein (ChREBP), fatty acid synthase (FAS), and acetyl-CoA carboxylase (ACC) were evaluated at 2 and 8 weeks postoperatively. RESULTS Compared with sham group, DJB induced rapid and significant improvements in glucose homeostasis and insulin sensitivity independently of weight loss and calorie restriction. The DJB-operated rats exhibited lower liver TG content and decreased hepatic SREBP-1, ChREBP, ACC, and FAS at 8 weeks postoperatively. CONCLUSIONS DJB alleviated hepatic fat accumulation and downregulated the key transcriptional regulators and enzymes involved in hepatic de novo lipogenesis, which might contribute to improved hepatic insulin sensitivity and glucose homeostasis after DJB.
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Ishikawa T, Graham JL, Stanhope KL, Havel PJ, La Merrill MA. Effect of DDT exposure on lipids and energy balance in obese Sprague-Dawley rats before and after weight loss. Toxicol Rep 2015; 2:990-995. [PMID: 28962439 PMCID: PMC5598246 DOI: 10.1016/j.toxrep.2015.07.005] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2015] [Revised: 07/03/2015] [Accepted: 07/05/2015] [Indexed: 11/30/2022] Open
Abstract
Dichlorodiphenyltrichloroethane (DDT) and its metabolites accumulate in adipose tissue through dietary exposure, and have been proposed to contribute to the development of abdominal obesity, insulin resistance and dyslipidemia. Toxicity may also result when DDT and its metabolites are released from adipose tissue into the bloodstream as a result of rapid weight loss. We hypothesized that DDT-exposed rats fed a high fat diet (HFD) followed by 60% calorie restriction would have an adverse metabolic response to rapid weight loss. To test this, we exposed obese Sprague-Dawley (SD) rats to DDT and a HFD over one month followed by 60% calorie restricted diet for two weeks, and examined metabolic parameters throughout the study. During the HFD feeding period, DDT-exposed rats had significantly elevated postprandial non-esterified fatty acids (NEFAs) and decreased body temperature compared with control rats. During calorie restriction, DDT-exposed rats had lowered food efficiency (weight gained/calories consumed), body temperature, and circulating TSH. Our findings suggest that exposure to DDT may impairs metabolic substrate utilization in rats during dynamic periods of weight gain and weight loss.
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Key Words
- CR, caloric restriction
- CVD, cardiovascular disease
- DDE
- DDE, dichlorodiphenyldichloroethylene
- DDT
- DDT, dichlorodiphenyltrichloroethane
- Dyslipidemia
- Food efficiency
- HFD, high fat diet
- NEFA, non esterified fatty acid
- OLTT, oral lipid tolerance test
- SD, Sprague Dawley
- T2DM, type 2 diabetes mellitus
- T3, triiodothyronine
- T4, thyroxine
- TG, triglyceride
- TSH, thyroid-stimulating hormone
- Thermoregulation
- Thyroid hormone
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Affiliation(s)
- Tomoko Ishikawa
- Department of Environmental Toxicology, University of California Davis, Davis, CA 95616, USA
| | - James L. Graham
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA
- Department of Nutrition, University of California Davis, Davis, CA 95616, USA
| | - Kimber L. Stanhope
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA
- Department of Nutrition, University of California Davis, Davis, CA 95616, USA
| | - Peter J. Havel
- Department of Molecular Biosciences, School of Veterinary Medicine, University of California Davis, Davis, CA 95616, USA
- Department of Nutrition, University of California Davis, Davis, CA 95616, USA
| | - Michele A. La Merrill
- Department of Environmental Toxicology, University of California Davis, Davis, CA 95616, USA
- Correspondence to: Department of Toxicology, One Shields Avenue, Davis, CA 95616, USA.
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Penney NC, Kinross J, Newton RC, Purkayastha S. The role of bile acids in reducing the metabolic complications of obesity after bariatric surgery: a systematic review. Int J Obes (Lond) 2015; 39:1565-74. [PMID: 26081915 DOI: 10.1038/ijo.2015.115] [Citation(s) in RCA: 104] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2014] [Revised: 03/05/2015] [Accepted: 05/31/2015] [Indexed: 02/06/2023]
Abstract
BACKGROUND Bariatric surgery is currently the most efficacious treatment for obesity and its associated metabolic co-morbidities, such as diabetes. The metabolic improvements occur through both weight-dependent and weight-independent mechanisms. Bile acids (BAs) have emerged as key signalling molecules that have a central role in modulating many of the physiological effects seen after bariatric surgery. This systematic review assesses the evidence from both human and animal studies for the role of BAs in reducing the metabolic complications of obesity following bariatric surgery. METHODS We conducted a systematic search of Medline and Embase databases to identify all articles investigating the role of BAs in mediating the metabolic changes observed following bariatric surgery in both animal and human studies. Boolean logic was used with relevant search terms, including the following MeSH terms: 'bile acids and salts', 'bariatric surgery', 'metabolic surgery', 'gastrointestinal tract/surgery' and 'obesity/surgery'. RESULTS Following database searches (n=1197), inclusion from bibliography searches (n=2) and de-duplication (n=197), 1002 search results were returned. Of these, 132 articles were selected for full-text review, of which 38 articles were deemed relevant and included in the review. The findings support the effects of BAs on satiety, lipid and cholesterol metabolism, incretins and glucose homoeostasis, energy metabolism, gut microbiota and endoplasmic reticulum stress following bariatric surgery. Many of these metabolic effects are modulated through the BA receptors FXR and TGR5. We also explore a possible link between BAs and carcinogenesis following bariatric surgery. CONCLUSIONS Overall there is good evidence to support the role of BAs in the metabolic effects of bariatric surgery through the above mechanisms. BAs could serve as a novel therapeutic pharmacological target for the treatment of obesity and its associated co-morbidities.
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Affiliation(s)
- N C Penney
- Department of Surgery and Cancer, St Mary's Hospital, Imperial College London, London, UK
| | - J Kinross
- Department of Surgery and Cancer, St Mary's Hospital, Imperial College London, London, UK
| | - R C Newton
- Department of Surgery and Cancer, St Mary's Hospital, Imperial College London, London, UK
| | - S Purkayastha
- Department of Surgery and Cancer, St Mary's Hospital, Imperial College London, London, UK
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Arble DM, Sandoval DA, Seeley RJ. Mechanisms underlying weight loss and metabolic improvements in rodent models of bariatric surgery. Diabetologia 2015; 58:211-20. [PMID: 25374275 PMCID: PMC4289431 DOI: 10.1007/s00125-014-3433-3] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/15/2014] [Accepted: 10/03/2014] [Indexed: 02/06/2023]
Abstract
Obesity is a growing health risk with few successful treatment options and fewer still that target both obesity and obesity-associated comorbidities. Despite ongoing scientific efforts, the most effective treatment option to date was not developed from basic research but by surgeons observing outcomes in the clinic. Bariatric surgery is the most successful treatment for significant weight loss, resolution of type 2 diabetes and the prevention of future weight gain. Recent work with animal models has shed considerable light on the molecular underpinnings of the potent effects of these 'metabolic' surgical procedures. Here we review data from animal models and how these studies have evolved our understanding of the critical signalling systems that mediate the effects of bariatric surgery. These insights could lead to alternative therapies able to accomplish effects similar to bariatric surgery in a less invasive manner.
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Maleckas A, Venclauskas L, Wallenius V, Lönroth H, Fändriks L. Surgery in the treatment of type 2 diabetes mellitus. Scand J Surg 2015; 104:40-7. [DOI: 10.1177/1457496914561140] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
Background and Aims: The prevalence of diabetes is increasing worldwide, and most of the cases are type 2 diabetes mellitus. The relationship between type 2 diabetes mellitus and obesity is well established, and surgical treatment is widely used for obese patients with type 2 diabetes mellitus. The aim was to present current knowledge about the possible mechanisms responsible for glucose control after surgical procedures and to review the surgical treatment results. Material and Methods: Medical literature was searched for the articles presenting the impact of surgical treatment on glycemic control, long-term results, and possible mechanisms of action among obese individuals with type 2 diabetes mellitus. Results: Remission of type 2 diabetes mellitus after bariatric surgery depends on the definition of the remission used. Complete remission rate after surgery with the new criteria is lower than was considered before. Randomized controlled studies demonstrate that surgery is superior to best medical treatment for the patients with type 2 diabetes mellitus. The recurrence of type 2 diabetes mellitus after bariatric surgery is observed in up to 40% of cases with ≥5 years of follow-up. Despite the recurrence of type 2 diabetes mellitus in this group, better glycemic control and lower risk of macrovascular complications are present. Incretin effects on glycemic control after bariatric surgery are well described, but the role of other possible mechanisms (bile acids, microbiota, intestinal gluconeogenesis) in humans is unclear. Conclusion: Surgery is an effective treatment of type 2 diabetes mellitus in obese patients. The most optimal surgical procedure for the treatment of obese patients with type 2 diabetes mellitus is still to be established. More research is needed to explore the mechanisms of glycemic control after bariatric surgery.
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Affiliation(s)
- A. Maleckas
- Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
- Department of Surgery, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - L. Venclauskas
- Department of Surgery, Medical Academy, Lithuanian University of Health Sciences, Kaunas, Lithuania
| | - V. Wallenius
- Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - H. Lönroth
- Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
| | - L. Fändriks
- Department of Gastrosurgical Research and Education, Institute of Clinical Sciences, The Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
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Kwon Y, Jung Kim H, Lo Menzo E, Park S, Szomstein S, Rosenthal RJ. A systematic review and meta-analysis of the effect of Billroth reconstruction on type 2 diabetes: A new perspective on old surgical methods. Surg Obes Relat Dis 2015; 11:1386-95. [PMID: 25892345 DOI: 10.1016/j.soard.2015.01.001] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2014] [Revised: 12/24/2014] [Accepted: 01/03/2015] [Indexed: 01/30/2023]
Abstract
BACKGROUND Studies have reported that Billroth II (BII) reconstruction after subtotal gastrectomy for cancer or intractable ulcers can more effectively improve type 2 diabetes mellitus (T2D) than Billroth I (BI) reconstruction by allowing patients to achieve normoglycemia without or with lower doses of diabetes medications. Thus, we conducted a systematic review and meta-analysis of studies to assess the effect of Billroth techniques on postoperative T2D status and identify the clinical predictors of amelioration. METHODS The MEDLINE and EMBASE databases and the Cochrane Central Register of Controlled Trials were searched for studies using a list of keywords. Moreover, reference lists from relevant review articles were searched. We included studies comparing BI with BII reconstruction as well as those with available outcome data for postoperative T2D status. Of the 52 potentially relevant studies, 8 met the inclusion criteria. Data were combined using a fixed- or random-effects model. RESULTS Compared with the BI group, the relative risk for postoperative T2D remission and amelioration in the BII group was 1.49 (95% confidence interval [CI], 1.01 to 2.19) and 1.31 (95% CI, 1.11 to 1.54), respectively. Patients who achieved amelioration had a higher body mass index than those who did not (weighted mean difference, .88 kg/m(2); 95% CI, .38 to 1.37) and shorter duration of diabetes (weighted mean difference, -0.40; 95% CI, -0.23 to -.70) at baseline. CONCLUSIONS BII reconstruction after subtotal gastrectomy for cancer or intractable ulcers more effectively improved T2D than BI reconstruction. Thus, BII reconstruction may provide a treatment strategy for diabetic patients with gastric cancer or ulcers and enable metabolic surgery for nonobese patients.
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Affiliation(s)
- Yeongkeun Kwon
- Metabolic and Bariatric Center, Department of Family Medicine, Korea University College of Medicine, Seoul, Korea
| | - Hyun Jung Kim
- Institute for Evidence-based Medicine, The Korean Branch of Australasian Cochrane Center, Department of Preventive Medicine, Korea University College of Medicine, Seoul, Korea
| | - Emanuele Lo Menzo
- Bariatric and Metabolic Institute, Section of Minimally Invasive Surgery, Cleveland Clinic Florida, Weston, Florida
| | - Sungsoo Park
- Metabolic and Bariatric Centre, Division of Upper Gastrointestinal Surgery, Department of Surgery, Korea University College of Medicine, Seoul, Korea.
| | - Samuel Szomstein
- Bariatric and Metabolic Institute, Section of Minimally Invasive Surgery, Cleveland Clinic Florida, Weston, Florida
| | - Raul J Rosenthal
- Bariatric and Metabolic Institute, Section of Minimally Invasive Surgery, Cleveland Clinic Florida, Weston, Florida
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Jurowich CF, Otto C, Rikkala PR, Wagner N, Vrhovac I, Sabolić I, Germer CT, Koepsell H. Ileal Interposition in Rats with Experimental Type 2 Like Diabetes Improves Glycemic Control Independently of Glucose Absorption. J Diabetes Res 2015; 2015:490365. [PMID: 26185767 PMCID: PMC4491588 DOI: 10.1155/2015/490365] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2015] [Revised: 06/05/2015] [Accepted: 06/07/2015] [Indexed: 02/08/2023] Open
Abstract
Bariatric operations in obese patients with type 2 diabetes often improve diabetes before weight loss is observed. In patients mainly Roux-en-Y-gastric bypass with partial stomach resection is performed. Duodenojejunal bypass (DJB) and ileal interposition (IIP) are employed in animal experiments. Due to increased glucose exposition of L-cells located in distal ileum, all bariatric surgery procedures lead to higher secretion of antidiabetic glucagon like peptide-1 (GLP-1) after glucose gavage. After DJB also downregulation of Na(+)-d-glucose cotransporter SGLT1 was observed. This suggested a direct contribution of decreased glucose absorption to the antidiabetic effect of bariatric surgery. To investigate whether glucose absorption is also decreased after IIP, we induced diabetes with decreased glucose tolerance and insulin sensitivity in male rats and investigated effects of IIP on diabetes and SGLT1. After IIP, we observed weight-independent improvement of glucose tolerance, increased insulin sensitivity, and increased plasma GLP-1 after glucose gavage. The interposed ileum was increased in diameter and showed increased length of villi, hyperplasia of the epithelial layer, and increased number of L-cells. The amount of SGLT1-mediated glucose uptake in interposed ileum was increased 2-fold reaching the same level as in jejunum. Thus, improvement of glycemic control by bariatric surgery does not require decreased glucose absorption.
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Affiliation(s)
- Christian Ferdinand Jurowich
- Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany
| | - Christoph Otto
- Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany
| | - Prashanth Reddy Rikkala
- Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, 97070 Würzburg, Germany
| | - Nicole Wagner
- Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, 97070 Würzburg, Germany
| | - Ivana Vrhovac
- Molecular Toxicology Unit, Institute for Medical Research & Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, Croatia
| | - Ivan Sabolić
- Molecular Toxicology Unit, Institute for Medical Research & Occupational Health, Ksaverska Cesta 2, 10000 Zagreb, Croatia
| | - Christoph-Thomas Germer
- Department of General, Visceral, Vascular and Paediatric Surgery, University Hospital of Würzburg, Oberdürrbacher Straße 6, 97080 Würzburg, Germany
| | - Hermann Koepsell
- Institute of Anatomy and Cell Biology, University of Würzburg, Koellikerstraße 6, 97070 Würzburg, Germany
- Department of Molecular Plant Physiology and Biophysics, Julius-von-Sachs-Institute, University of Würzburg, Julius-von-Sachs-Platz 2, 97082 Würzburg, Germany
- *Hermann Koepsell:
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Maternal ileal interposition surgery confers metabolic improvements to offspring independent of effects on maternal body weight in UCD-T2DM rats. Obes Surg 2014; 23:2042-9. [PMID: 24036841 DOI: 10.1007/s11695-013-1076-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
BACKGROUND Increasing numbers of people are undergoing bariatric surgery, of which approximately half are women in their childbearing years. However, information on the long-term effects of maternal bariatric surgery in their children is lacking. Furthermore, since bariatric surgery is performed to reduce body weight, clinical studies have not been able to differentiate between benefits to the child due to maternal body weight loss versus other maternal postoperative metabolic changes. Therefore, we used the University of California, Davis, type 2 diabetes mellitus (UCD-T2DM) rat model to test the hypothesis that maternal ileal interposition (IT) surgery would confer beneficial metabolic effects in offspring, independent of effects on maternal body weight. METHODS IT surgery was performed on 2-month-old prediabetic female UCD-T2DM rats. Females were bred 3 weeks after surgery, and male pups were studied longitudinally. RESULTS Maternal IT surgery resulted in decreased body weight in offspring compared with sham offspring (P < 0.05). IT offspring exhibited improvements of glucose-stimulated insulin secretion and nutrient-stimulated glucagon-like peptide-2 (GLP-2) secretion (P < 0.05). Fasting plasma unconjugated bile acid concentrations were 4-fold lower in IT offspring compared with sham offspring at two months of age (P < 0.001). CONCLUSIONS Overall, maternal IT surgery confers modest improvements of body weight and improves insulin secretion and nutrient-stimulated GLP-2 secretion in offspring in the UCD-T2DM rat model of type 2 diabetes, indicating that this is a useful model for investigating the weight-independent metabolic effects of maternal bariatric surgery.
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Sun X, Zheng M, Song M, Bai R, Cheng S, Xing Y, Yuan H, Wang P. Ileal interposition reduces blood glucose levels and decreases insulin resistance in a type 2 diabetes mellitus animal model by up-regulating glucagon-like peptide-1 and its receptor. INTERNATIONAL JOURNAL OF CLINICAL AND EXPERIMENTAL PATHOLOGY 2014; 7:4136-4142. [PMID: 25120793 PMCID: PMC4129028] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 04/27/2014] [Accepted: 06/23/2014] [Indexed: 06/03/2023]
Abstract
This study is to explore the possible mechanism of ileal interposition (IT) treatment of glycemic control of the type 2 diabetes mellitus (T2DM) by establishing an IT animal model. Twelve T2DM rats (GK rats) of 8-week old were divided into GK IT surgery group (GK-IT) and GK sham group (GK-Sham). Six Wistar rats were used as the non-T2DM sham group (WS-Sham). Enzyme-linked immunosorbent assay was used to detect plasma insulin concentration and fasting pancreas glucagon-like peptide-1 (GLP-1) concentration changes. Homeostasis model assessment of insulin resistance was used to quantitatively measure insulin resistance. Glucagon-like peptide-1 receptor (GLP-1R) expression was detected by Western blotting. IT significantly decreased fasting blood glucose level and the oral glucose tolerance, and reduced insulin resistance of GK rats by increasing GLP-1 concentration and GLP-1R levels. The postoperative pancreatic β-cell apoptosis rate of GK-Sham group was significantly higher than those in the GK-IT group and the WS-Sham group. IT significantly reduces blood glucose and decreases insulin resistance by up-regulating GLP-1 concentrations and GLP-1R levels, which may contribute to insulin secretion of pancreatic β-cells and decreases apoptosis of pancreatic β-cell.
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Affiliation(s)
- Xu Sun
- Department of Gastrointestinal Tumor Surgery, Shandong Cancer Hospital440 Jiyan Road, Jinan 250117, Shandong, China
| | - Meizhu Zheng
- Breast Cancer Center, Shandong Cancer Hospital440 Jiyan Road, Jinan 250117, Shandong, China
| | - Maomin Song
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical UniversityBeijing 100050, China
| | - Rixing Bai
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical UniversityBeijing 100050, China
| | - Shi Cheng
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical UniversityBeijing 100050, China
| | - Ying Xing
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical UniversityBeijing 100050, China
| | - Huisheng Yuan
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical UniversityBeijing 100050, China
| | - Pilin Wang
- Department of General Surgery, Beijing Tiantan Hospital, Capital Medical UniversityBeijing 100050, China
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The better effect of Roux-en-Y gastrointestinal reconstruction on blood glucose of nonobese type 2 diabetes mellitus patients. Am J Surg 2014; 207:877-81. [DOI: 10.1016/j.amjsurg.2013.06.011] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2012] [Revised: 06/15/2013] [Accepted: 06/20/2013] [Indexed: 01/06/2023]
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Deterioration of plasticity and metabolic homeostasis in the brain of the UCD-T2DM rat model of naturally occurring type-2 diabetes. Biochim Biophys Acta Mol Basis Dis 2014; 1842:1313-23. [PMID: 24840661 DOI: 10.1016/j.bbadis.2014.05.007] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2014] [Revised: 05/06/2014] [Accepted: 05/07/2014] [Indexed: 02/07/2023]
Abstract
The rising prevalence of type-2 diabetes is becoming a pressing issue based on emerging reports that T2DM can also adversely impact mental health. We have utilized the UCD-T2DM rat model in which the onset of T2DM develops spontaneously across time and can serve to understand the pathophysiology of diabetes in humans. An increased insulin resistance index and plasma glucose levels manifested the onset of T2DM. There was a decrease in hippocampal insulin receptor signaling in the hippocampus, which correlated with peripheral insulin resistance index along the course of diabetes onset (r=-0.56, p<0.01). T2DM increased the hippocampal levels of 4-hydroxynonenal (4-HNE; a marker of lipid peroxidation) in inverse proportion to the changes in the mitochondrial regulator PGC-1α. Disrupted energy homeostasis was further manifested by a concurrent reduction in energy metabolic markers, including TFAM, SIRT1, and AMPK phosphorylation. In addition, T2DM influenced brain plasticity as evidenced by a significant reduction of BDNF-TrkB signaling. These results suggest that the pathology of T2DM in the brain involves a progressive and coordinated disruption of insulin signaling, and energy homeostasis, with profound consequences for brain function and plasticity. All the described consequences of T2DM were attenuated by treatment with the glucagon-like peptide-1 receptor agonist, liraglutide. Similar results to those of liraglutide were obtained by exposing T2DM rats to a food energy restricted diet, which suggest that normalization of brain energy metabolism is a crucial factor to counteract central insulin sensitivity and synaptic plasticity associated with T2DM.
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Hu C, Su Q, Li F, Zhang G, Sun D, Han H, Liu S, Hu S. Duodenal–Jejunal Bypass Improves Glucose Homeostasis in Association with Decreased Proinflammatory Response and Activation of JNK in the Liver and Adipose Tissue in a T2DM Rat Model. Obes Surg 2014; 24:1453-62. [DOI: 10.1007/s11695-014-1230-1] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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Acosta A, Abu Dayyeh BK, Port JD, Camilleri M. Recent advances in clinical practice challenges and opportunities in the management of obesity. Gut 2014; 63:687-95. [PMID: 24402654 PMCID: PMC4170188 DOI: 10.1136/gutjnl-2013-306235] [Citation(s) in RCA: 68] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Despite advances in understanding the roles of adiposity, food intake, GI and adipocyte-related hormones, inflammatory mediators, the gut-brain axis and the hypothalamic nervous system in the pathophysiology of obesity, the effects of different therapeutic interventions on those pathophysiological mechanisms are controversial. There are still no low-cost, safe, effective treatments for obesity and its complications. Currently, bariatric surgical approaches targeting the GI tract are more effective than non-surgical approaches in inducing weight reduction and resolving obesity-related comorbidities. However, current guidelines emphasise non-surgical approaches through lifestyle modification and medications to achieve slow weight loss, which is not usually sustained and may be associated with medication-related side effects. This review analyses current central, peripheral or hormonal targets to treat obesity and addresses challenges and opportunities to develop novel approaches for obesity.
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Affiliation(s)
- Andres Acosta
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Barham K. Abu Dayyeh
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - John D. Port
- Division of Neuroradiology, Department of Radiology, Mayo Clinic College of Medicine, Rochester, Minnesota
| | - Michael Camilleri
- Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota
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Hu C, Zhang G, Sun D, Han H, Hu S. Duodenal-jejunal bypass improves glucose metabolism and adipokine expression independently of weight loss in a diabetic rat model. Obes Surg 2014; 23:1436-44. [PMID: 23636998 DOI: 10.1007/s11695-013-0976-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND There is accumulating evidence that adipokines lead to a proinflammatory state, which plays crucial roles in insulin resistance and development of type 2 diabetes mellitus (T2DM). Previous studies demonstrated that weight loss after bariatric surgery is accompanied by a suppression of the proinflammatory state. However, the effect of bariatric surgery on adipokine expression beyond weight loss is still elusive. The aim of this study was to investigate the effect of duodenal-jejunal bypass (DJB) on glucose homeostasis and adipokine expression independently of weight loss. METHODS A T2DM rat model was developed by a high-fat diet and low dose of streptozotocin. Twenty-one diabetic rats and 10 age-matched SD rats were randomly assigned to the DJB group, sham-DJB (S-DJB) group, and control group. For 12 weeks after surgery, their body weight, food intake, glucose homeostasis, lipid parameters, serum adipokine levels, and adipokine gene expression in the mesocolon adipose tissue were measured. RESULTS Compared to the S-DJB group, DJB induced significant and sustained glycemic control with improved insulin sensitivity and glucose tolerance independently of weight loss. DJB improved the lipid metabolism by decreasing fasting free fatty acids and triglycerides. Serum leptin and IL-6 significantly decreased 12 weeks after DJB, whereas adiponectin increased and TNF-α remained unchanged. The mRNA expression levels of leptin, TNF-α, and IL-6 decreased, whereas adiponectin increased in the mesocolon adipose tissue. CONCLUSION DJB reduced the proinflammatory adipokines and increased the anti-inflammatory adipokines independently of weight loss, which may contribute to the improvement of insulin sensitivity.
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Affiliation(s)
- Chunxiao Hu
- Department of General Surgery, Qilu Hospital of Shandong University, 107#, Wenhua Xi Road, Jinan 250012, Shandong, PR China
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O'Brien CS, Wang G, McGinty J, Agénor KK, Dutia R, Colarusso A, Park K, Koshy N, Laferrère B. Effects of gastrogastric fistula repair on weight loss and gut hormone levels. Obes Surg 2014; 23:1294-301. [PMID: 23549962 DOI: 10.1007/s11695-013-0917-z] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Abstract
BACKGROUND Weight regain after gastric bypass (GBP) can be associated with a gastrogastric fistula (GGF), in which a channel forms between the gastric pouch and gastric remnant, allowing nutrients to pass through the "old route" rather than bypassing the duodenum. To further understand the mechanisms by which GGF may lead to weight regain, we investigated gut hormone levels in GBP patients with a GGF, before and after repair. MATERIALS AND METHODS Seven post-GBP subjects diagnosed with GGF were studied before and 4 months after GGF repair. Another cohort of 22 GBP control subjects without GGF complication were studied before and 1 year post-GBP. All subjects underwent a 50-g oral glucose tolerance test and blood was collected from 0-120 min for glucose, insulin, ghrelin, PYY3-36, GIP, and GLP-1 levels. RESULTS Four months after GGF repair subjects lost 6.0 ± 3.9 kg and had significantly increased postprandial PYY3-36 levels. After GGF repair, fasting and postprandial ghrelin levels decreased and were strongly correlated with weight loss. The insulin response to glucose also tended to be increased after GGF repair, however no concomitant increase in GLP-1 was observed. Compared to the post-GBP group, GLP-1 and PYY3-36 levels were significantly lower before GGF repair; however, after GGF repair, PYY3-36 levels were no longer lower than the post-GBP group. CONCLUSIONS These data utilize the GGF model to highlight the possible role of duodenal shunting as a mechanism of sustained weight loss after GBP, and lend support to the potential link between blunted satiety peptide release and weight regain.
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Affiliation(s)
- Ciaran S O'Brien
- New York Obesity Nutrition Research Center, Department of Medicine, St Luke's Roosevelt Hospital Center, 1111 Amsterdam Avenue, New York, NY 10025, USA
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Hansen CF, Vassiliadis E, Vrang N, Sangild PT, Cummings BP, Havel P, Jelsing J. The effect of ileal interposition surgery on enteroendocrine cell numbers in the UC Davis type 2 diabetes mellitus rat. ACTA ACUST UNITED AC 2014; 189:31-9. [PMID: 24512816 DOI: 10.1016/j.regpep.2014.01.002] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2013] [Revised: 01/09/2014] [Accepted: 01/31/2014] [Indexed: 02/07/2023]
Abstract
AIM To investigate the short-term effect of ileal interposition (IT) surgery on gut morphology and enteroendocrine cell numbers in the pre-diabetic UC Davis type 2 diabetes mellitus (UCD-T2DM) rat. STUDY DESIGN Two-month old male UCD-T2DM rats underwent either sham (n=5) or IT (n=5) surgery. Intestines were collected 1.5months after surgery. The jejunum, ileum and colon regions were processed for histochemical and immunohistochemical labeling and stereological analyses of changes in gut morphometry and number of enteroendocrine cells. RESULTS Stereological analysis showed that intestinal volume, luminal surface area and the number of all chromogranin A-positive enteroendocrine cells were markedly increased in the IT rats compared with sham-operated animals. Subanalyses of the glucagon-like peptide 2, cholecystokinin, serotonin cells and the neurotensin immunoreactive sub-pool of enteroendocrine cells in the IT region revealed an increase in numbers across phenotypes. However, the density of the different cell types varied. CONCLUSION IT surgery in the UCD-T2DM rat leads to rapid alterations in gut morphometry and an increase in the number of enteroendocrine cells. This effect may potentially explain why IT surgery delays the onset of type 2 diabetes in the UCD-T2DM rat.
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Affiliation(s)
- Carl Frederik Hansen
- Gubra, Hørsholm, Denmark; Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark
| | | | | | - Per T Sangild
- Department of Human Nutrition, University of Copenhagen, Frederiksberg, Denmark
| | - Bethany P Cummings
- Department of Biomedical Sciences, School of Veterinary Medicine, Cornell University, Ithaca, NY, USA
| | - Peter Havel
- Department of Molecular Biosciences, University of California, Davis, CA, USA
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Cohen R, Caravatto PP, Petry T. Metabolic Surgery for Type 2 Diabetes in Patients with a BMI of <35 kg/m(2): A Surgeon's Perspective. Obes Surg 2014; 23:809-18. [PMID: 23564465 DOI: 10.1007/s11695-013-0930-2] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Bariatric surgery was developed with the aim of weight reduction. Success was defined only by excess weight loss. Other indices of resolution of metabolic comorbidities were reported, but were mostly secondary. Several communications have reported that regardless of body mass index (BMI), complete or partial remission of type 2 diabetes mellitus (T2DM) is possible. These results mostly occur before weight loss, positioning metabolic surgery as a good tool for controlling the current T2DM epidemic. Medical treatment is evolving, but is expensive and not risk-free. Surgery aimed mainly at diseases such as diabetes and not weight loss are referred to as "metabolic surgery." Metabolic surgery has been proven to be safe and effective, and although more data are needed, it is unquestionable that a new discipline has been founded. Metabolic surgery can effectively treat T2DM in individuals with any BMI, including that below 35 kg/m(2).
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Affiliation(s)
- Ricardo Cohen
- The Center of Excellence for Metabolic and Bariatric Surgery, Hospital Oswaldo Cruz, São Paulo, Brazil.
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Nguyen KT, Korner J. The sum of many parts: potential mechanisms for improvement in glucose homeostasis after bariatric surgery. Curr Diab Rep 2014; 14:481. [PMID: 24705810 PMCID: PMC4059201 DOI: 10.1007/s11892-014-0481-5] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
Bariatric surgery has emerged as the most durably effective treatment of type 2 diabetes (DM). However, the mechanisms governing improvement in glucose homeostasis have yet to be fully elucidated. In this review we discuss the various types of surgical interventions and the multitude of factors that potentially mediate the effects on glycemia, such as altered delivery of nutrients to the distal ileum, duodenal exclusion, gut hormone changes, bile acid reabsorption, and amino acid metabolism. Accumulating evidence that some of these changes seem to be independent of weight loss questions the rationale of using body mass index as the major indication for surgery in diabetic patients. Understanding the complex mechanisms and interactions underlying improved glycemic control could lead to novel therapeutic targets and would also allow for greater individualization of therapy and optimization of surgical outcomes.
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Affiliation(s)
- Kim T. Nguyen
- Columbia University Medical Center, 630 West 168th St, PH 8 West, Room 864, New York, NY 10032, USA
| | - Judith Korner
- Weight Control Center, Columbia University Medical Center, 650 West 168th St, Black Bldg, Room 905, New York, NY 10032, USA,
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