|
1
|
Mohanty I, Allaband C, Mannochio-Russo H, El Abiead Y, Hagey LR, Knight R, Dorrestein PC. The changing metabolic landscape of bile acids - keys to metabolism and immune regulation. Nat Rev Gastroenterol Hepatol 2024; 21:493-516. [PMID: 38575682 DOI: 10.1038/s41575-024-00914-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/14/2024] [Indexed: 04/06/2024]
Abstract
Bile acids regulate nutrient absorption and mitochondrial function, they establish and maintain gut microbial community composition and mediate inflammation, and they serve as signalling molecules that regulate appetite and energy homeostasis. The observation that there are hundreds of bile acids, especially many amidated bile acids, necessitates a revision of many of the classical descriptions of bile acids and bile acid enzyme functions. For example, bile salt hydrolases also have transferase activity. There are now hundreds of known modifications to bile acids and thousands of bile acid-associated genes, especially when including the microbiome, distributed throughout the human body (for example, there are >2,400 bile salt hydrolases alone). The fact that so much of our genetic and small-molecule repertoire, in both amount and diversity, is dedicated to bile acid function highlights the centrality of bile acids as key regulators of metabolism and immune homeostasis, which is, in large part, communicated via the gut microbiome.
Collapse
Affiliation(s)
- Ipsita Mohanty
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Celeste Allaband
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA
| | - Helena Mannochio-Russo
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Yasin El Abiead
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA
| | - Lee R Hagey
- Department of Medicine, University of California San Diego, San Diego, CA, USA
| | - Rob Knight
- Department of Pediatrics, University of California San Diego School of Medicine, La Jolla, CA, USA
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA
- Department of Computer Science and Engineering, University of California San Diego, La Jolla, CA, USA
- Department of Bioengineering, University of California San Diego, La Jolla, CA, USA
| | - Pieter C Dorrestein
- Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
- Center for Microbiome Innovation, University of California San Diego, La Jolla, CA, USA.
- Department of Pharmacology, University of California San Diego, La Jolla, CA, USA.
- Collaborative Mass Spectrometry Innovation Center, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego, La Jolla, CA, USA.
| |
Collapse
|
|
2
|
Jin M, Zou T, Huang H, Chen M, Zou H, Chen B, Lai C, Li H, Zhang P. The Effect of Coenzyme Q10 Supplementation on Bile Acid Metabolism: Insights from Network Pharmacology, Molecular Docking, and Experimental Validation. Mol Nutr Food Res 2024; 68:e2400147. [PMID: 38643378 DOI: 10.1002/mnfr.202400147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/29/2024] [Revised: 03/22/2024] [Indexed: 04/22/2024]
Abstract
SCOPE Bile acids play a crucial role in lipid absorption and the regulation of lipid, glucose, and energy homeostasis. Coenzyme Q10 (CoQ10), a lipophilic antioxidant, has been recognized for its positive effects on obesity and related glycolipid metabolic disorders. However, the relationship between CoQ10 and bile acids has not yet been evaluated. METHODS AND RESULTS This study assesses the impact of CoQ10 treatment on bile acid metabolism in mice on a high-fat diet using Ultra-Performance Liquid Chromatography-tandem Mass Spectrometry. CoQ10 reverses the reduction in serum and colonic total bile acid levels and alters the bile acid profile in mice that are caused by a high-fat diet. Seventeen potential targets of CoQ10 in bile acid metabolism are identified by network pharmacology, with six being central to the mechanism. Molecular docking shows a high binding affinity of CoQ10 to five of these key targets. Further analyses indicate that farnesoid X (FXR) receptor and Takeda G-protein coupled receptor 5 (TGR5) may be crucial targets for CoQ10 to regulate bile acid metabolism and exert beneficial effects. CONCLUSION This study sheds light on the impact of CoQ10 in bile acids metabolism and offers a new perspective on the application of CoQ10 in metabolic health.
Collapse
Affiliation(s)
- Mengcheng Jin
- School of Public Health, Guangdong Medical University, Dongguan, 523808, China
| | - Tangbin Zou
- The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, 523710, China
| | - Hairong Huang
- Southwest Hospital Jiangbei Area (The 958th hospital of Chinese People's Liberation Army), Chongqing, 400020, China
| | - Ming Chen
- School of Public Health, Guangdong Medical University, Dongguan, 523808, China
| | - Haoqi Zou
- School of Public Health, Guangdong Medical University, Dongguan, 523808, China
| | - Baoyan Chen
- School of Public Health, Guangdong Medical University, Dongguan, 523808, China
| | - Chengze Lai
- School of Public Health, Guangdong Medical University, Dongguan, 523808, China
| | - Huawen Li
- School of Public Health, Guangdong Medical University, Dongguan, 523808, China
| | - Peiwen Zhang
- School of Public Health, Guangdong Medical University, Dongguan, 523808, China
| |
Collapse
|
|
3
|
Hou Y, Zhai X, Wang X, Wu Y, Wang H, Qin Y, Han J, Meng Y. Research progress on the relationship between bile acid metabolism and type 2 diabetes mellitus. Diabetol Metab Syndr 2023; 15:235. [PMID: 37978556 PMCID: PMC10656899 DOI: 10.1186/s13098-023-01207-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2023] [Accepted: 11/02/2023] [Indexed: 11/19/2023] Open
Abstract
Bile acids, which are steroid molecules originating from cholesterol and synthesized in the liver, play a pivotal role in regulating glucose metabolism and maintaining energy balance. Upon release into the intestine alongside bile, they activate various nuclear and membrane receptors, influencing crucial processes. These bile acids have emerged as significant contributors to managing type 2 diabetes mellitus, a complex clinical syndrome primarily driven by insulin resistance. Bile acids substantially lower blood glucose levels through multiple pathways: BA-FXR-SHP, BA-FXR-FGFR15/19, BA-TGR5-GLP-1, and BA-TGR5-cAMP. They also impact blood glucose regulation by influencing intestinal flora, endoplasmic reticulum stress, and bitter taste receptors. Collectively, these regulatory mechanisms enhance insulin sensitivity, stimulate insulin secretion, and boost energy expenditure. This review aims to comprehensively explore the interplay between bile acid metabolism and T2DM, focusing on primary regulatory pathways. By examining the latest advancements in our understanding of these interactions, we aim to illuminate potential therapeutic strategies and identify areas for future research. Additionally, this review critically assesses current research limitations to contribute to the effective management of T2DM.
Collapse
Affiliation(s)
- Yisen Hou
- Department of Oncology Surgery, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, 710018, Shanxi, People's Republic of China
| | - Xinzhe Zhai
- Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, Shanxi, People's Republic of China
| | - Xiaotao Wang
- Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, Shanxi, People's Republic of China
| | - Yi Wu
- Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, Shanxi, People's Republic of China
| | - Heyue Wang
- Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, Shanxi, People's Republic of China
| | - Yaxin Qin
- Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, Shanxi, People's Republic of China
| | - Jianli Han
- Department of General Surgery, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Third Hospital of Shanxi Medical University, Taiyuan, 030032, Shanxi, People's Republic of China.
| | - Yong Meng
- Department of Oncology Surgery, Xi'an No.3 Hospital, The Affiliated Hospital of Northwest University, Xi'an, 710018, Shanxi, People's Republic of China.
| |
Collapse
|
|
4
|
Zhu L, Liao R, Huang J, Xiao C, Yang Y, Wang H, He D, Yan H, Yang C. Lactobacillus salivarius SNK-6 Regulates Liver Lipid Metabolism Partly via the miR-130a-5p/MBOAT2 Pathway in a NAFLD Model of Laying Hens. Cells 2022; 11:cells11244133. [PMID: 36552896 PMCID: PMC9776975 DOI: 10.3390/cells11244133] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2022] [Revised: 11/30/2022] [Accepted: 12/16/2022] [Indexed: 12/24/2022] Open
Abstract
Lactobacillus spp., as probiotics, have shown efficacy in alleviating nonalcoholic fatty liver disease (NAFLD). Here, we screened a new probiotic strain, Lactobacillus salivarius SNK-6 (L. salivarius SNK-6), which was isolated from the ileum of healthy Xinyang black-feather laying hens in China. We investigated the beneficial activity of L. salivarius SNK-6 in a NAFLD model in laying hens and found that L. salivarius SNK-6 inhibited liver fat deposition and decreased serum triglyceride levels and activity of aspartate transaminase and alanine transaminase. MBOAT2 (membrane-bound O-acyltransferase domain containing 2) was directly targeted by miR-130a-5p, which was downregulated in the liver of NAFLD laying hens but reversed after L. salivarius SNK-6 treatment. Downregulation of MBOAT2, L. salivarius SNK-6 supplementation in vivo, and L. salivarius SNK-6 cell culture treatment in vitro suppressed the mRNA expression of genes involved in the PPAR/SREBP pathway. In addition, 250 metabolites were identified in the supernatants of L. salivarius SNK-6 culture media, and most of them participated in metabolic pathways, including amino acid, carbohydrate, and lipid metabolism. Targeted metabolomic analysis revealed that acetate, butyrate, and propionate were the most abundant short-chain fatty acids, while cholic acid, ursodeoxycholic acid, chenodeoxycholic acid, and tauroursodeoxycholic acid were the four most-enriched bile acids among L. salivarius SNK-6 metabolites. This may have contributed to the reparative effect of L. salivarius SNK-6 in the NAFLD chicken model. Our study suggested that L. salivarius SNK-6 alleviated liver damage partly via the miR-130a-5p/MBOAT2 signaling pathway.
Collapse
Affiliation(s)
- Lihui Zhu
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
- National Poultry Research Center for Engineering and Technology, Shanghai 201106, China
| | - Rongrong Liao
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
| | - Jiwen Huang
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
- College of Animal Science and Technology, Zhejiang Agriculture and Forestry University, Hangzhou 311300, China
| | - Changfeng Xiao
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
- National Poultry Research Center for Engineering and Technology, Shanghai 201106, China
| | - Yunzhou Yang
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
| | - Huiying Wang
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
| | - Daqian He
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
| | - Huaxiang Yan
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
- Correspondence: (H.Y.); (C.Y.); Tel.: +86-216-220-5472 (H.Y. & C.Y.)
| | - Changsuo Yang
- Institute of Animal Husbandry and Veterinary Science, Shanghai Academy of Agricultural Sciences, Shanghai 201106, China
- National Poultry Research Center for Engineering and Technology, Shanghai 201106, China
- Correspondence: (H.Y.); (C.Y.); Tel.: +86-216-220-5472 (H.Y. & C.Y.)
| |
Collapse
|
|
5
|
Hu J, Zheng P, Qiu J, Chen Q, Zeng S, Zhang Y, Lin S, Zheng B. High-Amylose Corn Starch Regulated Gut Microbiota and Serum Bile Acids in High-Fat Diet-Induced Obese Mice. Int J Mol Sci 2022; 23:ijms23115905. [PMID: 35682591 PMCID: PMC9180756 DOI: 10.3390/ijms23115905] [Citation(s) in RCA: 3] [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: 03/06/2022] [Revised: 05/22/2022] [Accepted: 05/23/2022] [Indexed: 02/06/2023] Open
Abstract
Simple Summary High-amylose corn starch, as a kind of resistant starch, could profoundly regulate the gut microbiota and exert anti-obesity properties. Since the gut microbiota was found to improve metabolic health by altering circulating bile acids, therefore, here we investigated the association between the gut microbiota and serum bile acids in high fat diet induced obese mice fed with high-amylose corn starch. We found high-amylose corn starch could modulate the gut microbiota composition and partially restore the alternations in circulating bile acid profiles in obese mice. These influences on gut microbiota and circulating bile acids could be the underlying mechanisms of anti-obesity activity of high-amylose corn starch. Abstract High-amylose corn starch is well known for its anti-obesity activity, which is mainly based on the regulatory effects on gut microbiota. Recently, the gut microbiota has been reported to improve metabolic health by altering circulating bile acids. Therefore, in this study, the influence of high-amylose corn starch (HACS) on intestinal microbiota composition and serum bile acids was explored in mice fed with a high fat diet (HFD). The results demonstrated HACS treatment reduced HFD-induced body weight gain, hepatic lipid accumulation, and adipocyte hypertrophy as well as improved blood lipid profiles. Moreover, HACS also greatly impacted the gut microbiota with increased Firmicutes and decreased Bacteroidetes relative abundance being observed. Furthermore, compared to ND-fed mice, the mice with HFD feeding exhibited more obvious changes in serum bile acids profiles than the HFD-fed mice with the HACS intervention, showing HACS might restore HFD-induced alterations to bile acid composition in blood. In summary, our results suggested that the underlying mechanisms of anti-obesity activity of HACS may involve its regulatory effects on gut microbiota and circulating bile acids.
Collapse
Affiliation(s)
- Jiamiao Hu
- Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China; (J.H.); (P.Z.); (Q.C.); (S.Z.); (Y.Z.)
| | - Peiying Zheng
- Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China; (J.H.); (P.Z.); (Q.C.); (S.Z.); (Y.Z.)
| | - Jinhui Qiu
- Key Laboratory of Marine Biotechnology of Fujian Province, Institute of Oceanology, Fujian Agriculture and Forestry University, Fuzhou 350002, China;
| | - Qingyan Chen
- Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China; (J.H.); (P.Z.); (Q.C.); (S.Z.); (Y.Z.)
| | - Shaoxiao Zeng
- Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China; (J.H.); (P.Z.); (Q.C.); (S.Z.); (Y.Z.)
| | - Yi Zhang
- Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China; (J.H.); (P.Z.); (Q.C.); (S.Z.); (Y.Z.)
| | - Shaoling Lin
- College of Food Science, Fujian Agriculture and Forestry University, Fuzhou 350002, China
- Correspondence: (S.L.); (B.Z.); Tel.: +86-15606025198 (S.L.); +86-13705009016 (B.Z.)
| | - Baodong Zheng
- Engineering Research Centre of Fujian-Taiwan Special Marine Food Processing and Nutrition, Ministry of Education, Fuzhou 350002, China; (J.H.); (P.Z.); (Q.C.); (S.Z.); (Y.Z.)
- Correspondence: (S.L.); (B.Z.); Tel.: +86-15606025198 (S.L.); +86-13705009016 (B.Z.)
| |
Collapse
|
|
6
|
Akalestou E, Suba K, Lopez-Noriega L, Georgiadou E, Chabosseau P, Gallie A, Wretlind A, Legido-Quigley C, Leclerc I, Salem V, Rutter GA. Intravital imaging of islet Ca 2+ dynamics reveals enhanced β cell connectivity after bariatric surgery in mice. Nat Commun 2021; 12:5165. [PMID: 34453049 PMCID: PMC8397709 DOI: 10.1038/s41467-021-25423-8] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2020] [Accepted: 08/06/2021] [Indexed: 11/25/2022] Open
Abstract
Bariatric surgery improves both insulin sensitivity and secretion and can induce diabetes remission. However, the mechanisms and time courses of these changes, particularly the impact on β cell function, are difficult to monitor directly. In this study, we investigated the effect of Vertical Sleeve Gastrectomy (VSG) on β cell function in vivo by imaging Ca2+ dynamics in islets engrafted into the anterior eye chamber. Mirroring its clinical utility, VSG in mice results in significantly improved glucose tolerance, and enhanced insulin secretion. We reveal that these benefits are underpinned by augmented β cell function and coordinated activity across the islet. These effects involve changes in circulating GLP-1 levels which may act both directly and indirectly on the β cell, in the latter case through changes in body weight. Thus, bariatric surgery leads to time-dependent increases in β cell function and intra-islet connectivity which are likely to contribute to diabetes remission.
Collapse
Affiliation(s)
- Elina Akalestou
- grid.413629.b0000 0001 0705 4923Section of Cell Biology and Functional Genomics, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Kinga Suba
- grid.413629.b0000 0001 0705 4923Section of Cell Biology and Functional Genomics, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Livia Lopez-Noriega
- grid.413629.b0000 0001 0705 4923Section of Cell Biology and Functional Genomics, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Eleni Georgiadou
- grid.413629.b0000 0001 0705 4923Section of Cell Biology and Functional Genomics, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Pauline Chabosseau
- grid.413629.b0000 0001 0705 4923Section of Cell Biology and Functional Genomics, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Alasdair Gallie
- grid.413629.b0000 0001 0705 4923Central Biological Services (CBS) Hammersmith Hospital Campus, London, UK
| | - Asger Wretlind
- grid.419658.70000 0004 0646 7285Systems Medicine, Steno Diabetes Center, Gentofte, Copenhagen, Denmark
| | - Cristina Legido-Quigley
- grid.419658.70000 0004 0646 7285Systems Medicine, Steno Diabetes Center, Gentofte, Copenhagen, Denmark
| | - Isabelle Leclerc
- grid.413629.b0000 0001 0705 4923Section of Cell Biology and Functional Genomics, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Victoria Salem
- grid.413629.b0000 0001 0705 4923Section of Cell Biology and Functional Genomics, Imperial College London, Hammersmith Hospital Campus, London, UK ,grid.413629.b0000 0001 0705 4923Section of Investigative Medicine, Division of Diabetes, Endocrinology and Metabolism, Department of Metabolism, Digestion and Reproduction, Imperial College London, Hammersmith Hospital Campus, London, UK
| | - Guy A. Rutter
- grid.413629.b0000 0001 0705 4923Section of Cell Biology and Functional Genomics, Imperial College London, Hammersmith Hospital Campus, London, UK ,grid.59025.3b0000 0001 2224 0361Lee Kong Chian Imperial Medical School, Nanyang Technological University, Singapore, Singapore ,grid.14848.310000 0001 2292 3357Centre de Recherches du CHUM, University of Montreal, Montreal, QC Canada
| |
Collapse
|
|
7
|
Lee Y, Kim AH, Kim E, Lee S, Yu KS, Jang IJ, Chung JY, Cho JY. Changes in the gut microbiome influence the hypoglycemic effect of metformin through the altered metabolism of branched-chain and nonessential amino acids. Diabetes Res Clin Pract 2021; 178:108985. [PMID: 34329692 DOI: 10.1016/j.diabres.2021.108985] [Citation(s) in RCA: 22] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/10/2021] [Revised: 07/20/2021] [Accepted: 07/23/2021] [Indexed: 02/08/2023]
Abstract
AIMS Although metformin has been reported to affect the gut microbiome, the mechanism has not been fully determined. We explained the potential underlying mechanisms of metformin through a multiomics approach. METHODS An open-label and single-arm clinical trial involving 20 healthy Korean was conducted. Serum glucose and insulin concentrations were measured, and stool samples were collected to analyze the microbiome. Untargeted metabolomic profiling of plasma, urine, and stool samples was performed by GC-TOF-MS. Network analysis was applied to infer the mechanism of the hypoglycemic effect of metformin. RESULTS The relative abundances of Escherichia, Romboutsia, Intestinibacter, and Clostridium were changed by metformin treatment. Additionally, the relative abundances of metabolites, including carbohydrates, amino acids, and fatty acids, were changed. These changes were correlated with energy metabolism, gluconeogenesis, and branched-chain amino acid metabolism, which are major metabolic pathways related to the hypoglycemic effect. CONCLUSIONS We observed that specific changes in metabolites may affect hypoglycemic effects through both pathways related to AMPK activation and microbial changes. Energy metabolism was mainly related to hypoglycemic effects. In particular, branched-chain amino acid metabolism and gluconeogenesis were related to microbial metabolites. Our results will help uncover the potential underlying mechanisms of metformin through AMPK and the microbiome.
Collapse
Affiliation(s)
- Yujin Lee
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea.
| | - Andrew HyoungJin Kim
- Department of Medicine, Division of Infectious Diseases, Washington University School of Medicine, St. Louis, MO, USA.
| | - Eunwoo Kim
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea.
| | - SeungHwan Lee
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea.
| | - Kyung-Sang Yu
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
| | - In-Jin Jang
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea.
| | - Jae-Yong Chung
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea; Clinical Trials Center, Seoul National University Bundang Hospital, Seongnam, South Korea.
| | - Joo-Youn Cho
- Department of Clinical Pharmacology and Therapeutics, Seoul National University College of Medicine and Hospital, Seoul 03080, South Korea; Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, South Korea.
| |
Collapse
|
|
8
|
Abstract
Bile acids (BAs) are a family of hydroxylated steroids secreted by the liver that aid in the breakdown and absorption of dietary fats. BAs also function as nutrient and inflammatory signaling molecules, acting through cognate receptors, to coordinate host metabolism. Commensal bacteria in the gastrointestinal tract are functional modifiers of the BA pool, affecting composition and abundance. Deconjugation of host BAs creates a molecular network that inextricably links gut microtia with their host. In this review we highlight the roles of BAs in mediating this mutualistic relationship with a focus on those events that impact host physiology and metabolism.
Collapse
Affiliation(s)
- James C Poland
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - C Robb Flynn
- Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| |
Collapse
|
|
9
|
Chen W, Yin H, Zhang N, Liu W, Qu Q, Xiao J, Gong F, He X. Improvement of Postprandial Lipid Metabolism After Ileal Transposition in Non-obese Diabetic Rats. Obes Surg 2021; 31:1572-1578. [PMID: 33409975 DOI: 10.1007/s11695-020-05158-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2020] [Revised: 12/03/2020] [Accepted: 12/07/2020] [Indexed: 10/22/2022]
Abstract
BACKGROUND Ileal transposition (IT) could reduce obesity and improve type 2 diabetes mellitus (T2DM). The main aim of our study was to investigate lipid metabolism changes in T2DM rats after IT without a weight reduction effect. METHODS Thirty male diabetic rats were randomly divided into IT, sham IT (SI), and control groups. The levels of plasma cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs), and bile acid were measured. After sacrifice, the white adipose tissue, brown adipose tissue and liver were weighed. RESULTS IT induced significant improvement in glucose and lipid metabolism. There were no significant differences in the levels of cholesterol (P = 0.87), HDL (P = 0.70), LDL (P = 0.96), or TGs (P = 0.97) among the groups before surgery. After IT, the levels of cholesterol (P = 0.019), LDL (P = 0.004), and TGs (P < 0.001) were lower than those in the SI and control groups, while the level of HDL was not significantly different compared to those of the other groups (P = 0.437). Higher bile acid level (P = 0.001), lower white adipose tissue/total body weight ratio (P < 0.001), and lower liver/total body weight ratio (P = 0.003) were found in the IT group. The BAT/total body weight ratio in the IT group was higher than that in the SI or control groups (P = 0.002). CONCLUSIONS IT could improve lipid metabolism in diabetic rats.
Collapse
Affiliation(s)
- Weijie Chen
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing, 100730, People's Republic of China
| | - Haixin Yin
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing, 100730, People's Republic of China
| | - Ning Zhang
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing, 100730, People's Republic of China
| | - Wei Liu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing, 100730, People's Republic of China
| | - Qiang Qu
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing, 100730, People's Republic of China
| | - Jianchun Xiao
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing, 100730, People's Republic of China
| | - Fengying Gong
- Department of Endocrinology, Key Laboratory of Endocrinology of the Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing, 100730, People's Republic of China
| | - Xiaodong He
- Department of General Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Shuaifuyuan 1#, Beijing, 100730, People's Republic of China.
| |
Collapse
|
|
10
|
Cook J, Lehne C, Weiland A, Archid R, Ritze Y, Bauer K, Zipfel S, Penders J, Enck P, Mack I. Gut Microbiota, Probiotics and Psychological States and Behaviors after Bariatric Surgery-A Systematic Review of Their Interrelation. Nutrients 2020; 12:nu12082396. [PMID: 32785153 PMCID: PMC7468806 DOI: 10.3390/nu12082396] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2020] [Revised: 08/01/2020] [Accepted: 08/07/2020] [Indexed: 02/07/2023] Open
Abstract
The gastrointestinal (GI) microbiota plays an important role in health and disease, including brain function and behavior. Bariatric surgery (BS) has been reported to result in various changes in the GI microbiota, therefore demanding the investigation of the impact of GI microbiota on treatment success. The goal of this systematic review was to assess the effects of BS on the microbiota composition in humans and other vertebrates, whether probiotics influence postoperative health, and whether microbiota and psychological and behavioral factors interact. A search was conducted using PubMed and Web of Science to find relevant studies with respect to the GI microbiota and probiotics after BS, and later screened for psychological and behavioral parameters. Studies were classified into groups and subgroups to provide a clear overview of the outcomes. Microbiota changes were further assessed for whether they were specific to BS in humans through the comparison to sham operated controls in other vertebrate studies. Changes in alpha diversity appear not to be specific, whereas dissimilarity in overall microbial community structure, and increases in the abundance of the phylum Proteobacteria and Akkermansia spp. within the phylum Verrucomicrobia after surgery were observed in both human and other vertebrates studies and may be specific to BS in humans. Human probiotic studies differed regarding probiotic strains and dosages, however it appeared that probiotic interventions were not superior to a placebo for quality of life scores or weight loss after BS. The relationship between GI microbiota and psychological diseases in this context is unclear due to insufficient available data.
Collapse
Affiliation(s)
- Jessica Cook
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, 72072 Tübingen, Germany; (J.C.); (C.L.); (A.W.); (K.B.); (S.Z.); (P.E.)
| | - Christine Lehne
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, 72072 Tübingen, Germany; (J.C.); (C.L.); (A.W.); (K.B.); (S.Z.); (P.E.)
| | - Alisa Weiland
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, 72072 Tübingen, Germany; (J.C.); (C.L.); (A.W.); (K.B.); (S.Z.); (P.E.)
| | - Rami Archid
- Department of General, Visceral and Transplant Surgery, University Hospital, 72072 Tübingen, Germany;
| | - Yvonne Ritze
- Institute for Medical Psychology and Behavioral Neurobiology, University Hospital, 72072 Tübingen, Germany;
| | - Kerstin Bauer
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, 72072 Tübingen, Germany; (J.C.); (C.L.); (A.W.); (K.B.); (S.Z.); (P.E.)
| | - Stephan Zipfel
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, 72072 Tübingen, Germany; (J.C.); (C.L.); (A.W.); (K.B.); (S.Z.); (P.E.)
| | - John Penders
- Department of Medical Microbiology, School of Nutrition and Translational Research in Metabolism (NUTRIM) and Care and Public Health Research Institute(Caphri), Maastricht University Medical Centre, 6211 Maastricht, The Netherlands;
| | - Paul Enck
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, 72072 Tübingen, Germany; (J.C.); (C.L.); (A.W.); (K.B.); (S.Z.); (P.E.)
| | - Isabelle Mack
- Department of Psychosomatic Medicine and Psychotherapy, University Medical Hospital, 72072 Tübingen, Germany; (J.C.); (C.L.); (A.W.); (K.B.); (S.Z.); (P.E.)
- Correspondence: ; Tel.: +49-7071-2985614; Fax: +49-7071-294382
| |
Collapse
|
|
11
|
Xie X, Dong J, Lu G, Gao K, Li X, Mao W, Chen F, Tong Z, Li B, Li W. Increased circulating total bile acid levels were associated with organ failure in patients with acute pancreatitis. BMC Gastroenterol 2020; 20:222. [PMID: 32660430 PMCID: PMC7359019 DOI: 10.1186/s12876-020-01243-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 03/27/2020] [Indexed: 12/11/2022] Open
Abstract
Background Recent studies have shown that bile acids (BAs) are closely related to metabolic and inflammatory diseases. Our study aimed to investigate whether circulating total bile acid (TBA) levels were associated with the severity of acute pancreatitis (AP). Methods We retrospectively collected data on patients diagnosed with AP in a tertiary center from 01 January 2014 to 31 December 2016. The highest TBA value during the first 1,2,3,5,7 days after admission was determined as D1, D2, D3, D5, D7 TBAmax. Patients were divided into the high TBA (HTBA) group and the normal TBA (NTBA) group according to whether the TBAmax was ≥10 μmol/L. The prognosis and complications, including death, organ failure (OF) and pancreatic necrosis, were compared between the two groups. Logistic regression analysis and receiving operating characteristic (ROC) curve were used to evaluate the relationship between circulating TBA and organ failure in AP patients. Results Through stratified analysis of each time period, we found that the incidence of OF in the HTBA group was significantly higher than that in the NTBA group, and the AP severity classification in the HTBA group was more serious than that in the NTBA group. In addition, according to the D7 TBAmax values, the pancreatic necrosis rate, percutaneous catheter drainage (PCD) rate and mortality in the HTBA group were higher than those in the NTBA group. Multivariate regression analysis showed that HTBA (odds ratio (OR), 4.894; P = 0.002) was an independent risk factor for AP complicated with OF, which was verified in the grouping based on D7 TBAmax. ROC analysis revealed that a circulating D7 TBAmax cutoff point of 6.450 umol/L had optimal predictive value for the development of OF in AP patients with an area under the curve of the ROC curve (AUCROC) of 0.777. Conclusions The increase of circulating TBA in early stage of AP is independently related to organ failure, which indicates the adverse prognosis of AP patients.
Collapse
Affiliation(s)
- Xiaochun Xie
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People's Republic of China
| | - Jie Dong
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People's Republic of China
| | - Guotao Lu
- Pancreatic Center, Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, 225000, People's Republic of China
| | - Kun Gao
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People's Republic of China
| | - Xiaoyao Li
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People's Republic of China
| | - Wenjian Mao
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, South Medical University, Nanjing, 210002, People's Republic of China
| | - Faxi Chen
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People's Republic of China
| | - Zhihui Tong
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People's Republic of China.
| | - Baiqiang Li
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People's Republic of China.
| | - Weiqin Li
- Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Nanjing Medical University, Nanjing, 210002, People's Republic of China. .,Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, People's Republic of China. .,Surgical Intensive Care Unit (SICU), Department of General Surgery, Jinling Hospital, South Medical University, Nanjing, 210002, People's Republic of China.
| |
Collapse
|
|
12
|
Laessle C, Jin K, Seifert GJ, Timme-Bronsert S, Fichtner-Feigl S, Marjanovic G, Fink JM. Putting the Hindgut Hypothesis to the Test in a Diabetic Zucker Rat Model. Obes Surg 2020; 29:4000-4007. [PMID: 31367988 DOI: 10.1007/s11695-019-04079-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/27/2023]
Abstract
BACKGROUND The hindgut theory hypothesizes a key role of differential hindgut stimulation following metabolic procedures in ameliorating diabetes mellitus. We used two strategies to remove the hindgut from intestinal continuity in order to analyze its impact on diabetes mellitus. METHODS Loop duodeno-jejunostomy (DJOS) with exclusion of one-third of total intestinal length was performed in 3 groups of 9-week-old Zucker diabetic fatty rats. In group 1, no further alteration of the intestinal tract was made. Group 2 received additional ileal exclusion (IE). Group 3 underwent additional resection of 50% of the ileum with side-to-side ileocecal anastomosis (IR). One, 2, and 4 months after surgery, fasting blood glucose levels, oral glucose tolerance tests (OGTT), and glucose-stimulated hormone analyses were conducted, and bile acid blood levels were compared. Body weight was documented weekly. RESULTS In relation to DJOS, glucose control was not impaired in IR or IE. On the contrary, only IR could maintain preOP glucose values until 4 months. There were no significant weight differences between the groups. Confirming effective ileal diversion, bile acid blood levels were significantly higher in the DJOS group compared with both IR and IE (p = 0.0025 and p = 0.0047). Operative interventions had no impact on GLP-1 levels at any time point (ANOVA p > 0.05 for all). Insulin secretion was preserved in all groups. CONCLUSION This data supports the hypothesis that the mechanisms driving amelioration of diabetes mellitus are complex and cannot be reduced to the ileum.
Collapse
Affiliation(s)
- Claudia Laessle
- Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany.
| | - Ke Jin
- Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany
| | - Gabriel J Seifert
- Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany
| | - Sylvia Timme-Bronsert
- Faculty of Medicine, Institute of Pathology, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany
| | - Stefan Fichtner-Feigl
- Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany
| | - Goran Marjanovic
- Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany
| | - Jodok Matthias Fink
- Department of General and Visceral Surgery, Faculty of Medicine, Medical Center - University of Freiburg, Hugstetter Straße 55, 79106, Freiburg, Germany
| |
Collapse
|
|
13
|
Mesenteric arterial dysfunction in the UC Davis Type 2 Diabetes Mellitus rat model is dependent on pre-diabetic versus diabetic status and is sexually dimorphic. Eur J Pharmacol 2020; 879:173089. [PMID: 32320701 DOI: 10.1016/j.ejphar.2020.173089] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/18/2019] [Revised: 03/21/2020] [Accepted: 03/25/2020] [Indexed: 01/27/2023]
Abstract
Previous reports suggest that diabetes may differentially affect the vascular beds of females and males. However, there is insufficient evidence to establish the timeline of the vascular dysfunction in diabetes, specifically in relation to sex. Here, we determined whether mesenteric arterial function is altered in UC Davis Type-2 Diabetes Mellitus (UCD-T2DM) rats and if this occurs as early as the pre-diabetic stage of the disease. Specifically, we investigated whether vascular dysfunction differs between pre-diabetic or diabetic status and if this varies by sex. We measured the responses to endothelium-dependent and -independent vasorelaxant as well as vasoconstrictor agents and explored the potential mechanisms involved in sex-specific development of arterial dysfunction in UCD-T2DM rats. In addition, indices of insulin sensitivity were assessed. We report the reduced insulin sensitivity in pre-diabetic males and diabetic females. Vascular relaxation to acetylcholine was impaired to a greater extent in mesenteric artery from males in the pre-diabetic stage than in their female counterparts. In contrast, the arteries from females with diabetes exhibited a greater impairment to acetylcholine compared with diabetic males. Additionally, the sensitivity of mesenteric artery to contractile agents in females, but not in males, after the onset of diabetes was increased. Our data suggest that the reduced insulin sensitivity through AKT may predispose vessels to injury in the pre-diabetic stage in males. On the other hand, reduced insulin sensitivity as well as enhanced responsiveness to contractile agents may predispose arteries to injury in the diabetic stage in females.
Collapse
|
|
14
|
TGR5 Protects Against Colitis in Mice, but Vertical Sleeve Gastrectomy Increases Colitis Severity. Obes Surg 2020; 29:1593-1601. [PMID: 30623320 DOI: 10.1007/s11695-019-03707-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Bariatric surgery, such as vertical sleeve gastrectomy (VSG), is the most effective long-term treatment for obesity. However, there are conflicting reports on the effect of bariatric surgery on inflammatory bowel disease (IBD). Bariatric surgery increases bile acid concentrations, which can decrease inflammation by signaling through the bile acid receptor, TGR5. TGR5 signaling protects against chemically induced colitis in mice. VSG increases circulating bile acid concentrations to increase TGR5 signaling, which contributes to improved metabolic regulation after VSG. Therefore, we investigated the effect of VSG on chemically induced colitis development and the role of TGR5 in this context. METHODS VSG or sham surgery was performed in high fat diet-fed male Tgr5+/+ and Tgr5-/- littermates. Sham-operated mice were food restricted to match their body weight to VSG-operated mice. Colitis was induced with 2.5% dextran sodium sulfate (DSS) in water post-operatively. Body weight, energy intake, fecal scoring, colon histopathology, colonic markers of inflammation, goblet cell counts, and colonic microRNA-21 levels were assessed. RESULTS VSG decreased body weight independently of genotype. Consistent with previous work, genetic ablation of TGR5 increased the severity of DSS-induced colitis. Notably, despite the effect of VSG to decrease body weight and increase TGR5 signaling, VSG increased the severity of DSS-induced colitis. VSG-induced increases in colitis were associated with increased colonic expression of TNF-α, IL-6, MCP-1, and microRNA-21. CONCLUSIONS While our data demonstrate that TGR5 protects against colitis, they also demonstrate that VSG potentiates chemically induced colitis in mice. These data suggest that individuals undergoing VSG may be at increased risk for developing colitis; however, further study is needed.
Collapse
|
|
15
|
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]
|
|
16
|
Sawczyn T, Zimmermann J, Stygar D, Kukla M, Nabrdalik K, Matysiak N, Mielańczyk Ł, Karcz KW. Ileal Transposition (IT) Surgery Changing the Ultrastructure of the Transposed Segment as well as Jejunum. Histomorphometric and Electron Microscopy Analysis. Obes Surg 2019; 28:1232-1239. [PMID: 29101717 PMCID: PMC5968072 DOI: 10.1007/s11695-017-2992-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Objective Ileal transposition (IT) procedure leads to higher secretion of incretin hormones what is associated with a beneficial metabolic effect. However, IT will also have an influence on the related jejunum and ileum function. The aim of this research was to investigate the morphology of the jejunum and transposed ileum with the use of light and transmission electron microscopy (TEM) in order to determine the local alternations in the intestine resulting from the transposition. Methods Twenty male, 8-week-old, obese Zucker rats underwent IT and six of them sham surgery. To compare both groups, the transection was made at all corresponding ileum positions among both groups of animals. The ileal anastomoses among the rats of sham procedure were subsequently formed accordingly without IT. Three months following the surgery, the tissue samples of jejunum and ileum were harvested. Results A significant increase in villus length, a decrease in the crypt depth, and an increased thickness of mucosa-muscularis-serosa (MMS) as well as cellular hyperplasia, with increased mitochondrial density of the transposed ileum segment, were observed among the group of rats which underwent IT comparing to the ones undergoing sham surgery. In rats undergoing IT, microvillus degeneration in jejunum regions was observed. Conclusions Ileal transposition alters the morphology and ultrastructure of the ileum as well as the jejunum. Given that the microvillus membrane represents an important aspect of the enterocyte functions, a further biochemical and molecular research is necessary in order to assess whether the observed changes are beneficial or not and to explore the phenomenon of gut adaptability after metabolic surgery.
Collapse
Affiliation(s)
- Tomasz Sawczyn
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland.
| | - Julia Zimmermann
- Clinic of General, Visceral, Transplantation and Vascular Surgery, Hospital of the Ludwig Maximilian University, Munich, Germany
| | - Dominika Stygar
- Department of Physiology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Michał Kukla
- Department of Gastroenterology and Hepatology, School of Medicine in Katowice, Medical University of Silesia, Katowice, Poland
| | - Katarzyna Nabrdalik
- Department of Internal Medicine, Diabetology and Nephrology in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Natalia Matysiak
- Department of Histology and Embryology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Łukasz Mielańczyk
- Department of Histology and Embryology, School of Medicine with the Division of Dentistry in Zabrze, Medical University of Silesia, Katowice, Poland
| | - Konrad Wojciech Karcz
- Clinic of General, Visceral, Transplantation and Vascular Surgery, Hospital of the Ludwig Maximilian University, Munich, Germany
| |
Collapse
|
|
17
|
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.
Collapse
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
| |
Collapse
|
|
18
|
Debédat J, Amouyal C, Aron-Wisnewsky J, Clément K. Impact of bariatric surgery on type 2 diabetes: contribution of inflammation and gut microbiome? Semin Immunopathol 2019; 41:461-475. [PMID: 31025085 DOI: 10.1007/s00281-019-00738-3] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2019] [Accepted: 03/15/2019] [Indexed: 02/06/2023]
|
|
19
|
Wang W, Cheng Z, Wang Y, Dai Y, Zhang X, Hu S. Role of Bile Acids in Bariatric Surgery. Front Physiol 2019; 10:374. [PMID: 31001146 PMCID: PMC6454391 DOI: 10.3389/fphys.2019.00374] [Citation(s) in RCA: 45] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/06/2018] [Accepted: 03/18/2019] [Indexed: 12/11/2022] Open
Abstract
Bariatric surgery has been proved to be effective and sustainable in the long-term weight-loss and remission of metabolic disorders. However, the underlying mechanisms are still far from fully elucidated. After bariatric surgery, the gastrointestinal tract is manipulated, either anatomically or functionally, leading to changed bile acid metabolism. Accumulating evidence has shown that bile acids play a role in metabolic regulation as signaling molecules other than digestive juice. And most of the metabolism-beneficial effects are mediated through nuclear receptor FXR and membrane receptor TGR5, as well as reciprocal influence on gut microbiota. Bile diversion procedure is also performed on animals to recapitulate the benefits of bariatric surgery. It appears that bile acid alteration is an important component of bariatric surgery, and represents a promising target for the management of metabolic disorders.
Collapse
Affiliation(s)
- Wenting Wang
- Department of Obstetrics and Gynecology, The Second Hospital of Shandong University, Jinan, China
| | - Zhiqiang Cheng
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Yanlei Wang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Yong Dai
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Xiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| | - Sanyuan Hu
- Department of General Surgery, Qilu Hospital of Shandong University, Jinan, China
| |
Collapse
|
|
20
|
Abstract
Bile acids have important roles in the regulation of lipid, glucose and energy metabolism. Metabolic diseases linked to obesity, including type 2 diabetes mellitus and non-alcoholic fatty liver disease, are associated with dysregulation of bile acid homeostasis. Here, the basic chemistry and regulation of bile acids as well as their metabolic effects will be reviewed. Changes in circulating bile acids associated with obesity and related diseases will be reviewed. Finally, pharmaceutical manipulation of bile acid homeostasis as therapy for metabolic diseases will be outlined.
Collapse
Affiliation(s)
- Emma Rose McGlone
- Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| | - Stephen R Bloom
- Division of Diabetes, Endocrinology and Metabolism, Imperial College London, London, UK
| |
Collapse
|
|
21
|
Abstract
The obese brain is stressed and inflamed. This is mainly at the level of neurons and glial cells in the hypothalamus: a brain region where the adipokine leptin acts to control feeding and body weight. Relieving hypothalamic neuronal endoplasmic reticulum (ER) stress with the natural small molecule drugs celastrol or withaferin-A reverses the leptin resistance commensurate with obesity, producing a degree of weight loss found only with bariatric surgery. Here, recent evidence from rodent models of vertical sleeve gastrectomy (VSG) is brought to the fore which suggests that this particular bariatric surgical procedure may work in a similar fashion to celastrol and withaferin-A alongside remedying hypothalamic inflammation and gliosis. Thus, restoring and preserving healthy hypothalamic neuronal and glial cell function, be it by pharmacological or surgical means, ensures a negative energy balance in an environment constructed to promote a one - possibly through re-establishing communication between adipose tissue and the brain.
Collapse
Affiliation(s)
- Florian Seyfried
- Department of General, Visceral, Vascular and Pediatric Surgery, University Hospital Wuerzburg, Wuerzburg, 97080 Bavaria, Germany
| | - Mohammed K Hankir
- Department of Experimental Surgery, University Hospital Wuerzburg, Wuerzburg, 97080 Bavaria, Germany
| |
Collapse
|
|
22
|
Zhu H, Wang H, Zheng Z, Ye B, Ruan X, Zheng X, Li G. Ileal transposition rapidly improves glucose tolerance and gradually improves insulin resistance in non-obese type 2 diabetic rats. Gastroenterol Rep (Oxf) 2018; 6:291-297. [PMID: 30430018 PMCID: PMC6225830 DOI: 10.1093/gastro/goy027] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2018] [Revised: 03/04/2018] [Accepted: 06/26/2018] [Indexed: 02/06/2023] Open
Abstract
Background Many studies have confirmed that ileal transposition can improve type 2 diabetes mellitus (T2DM), accompanied by increased glucagon-like peptide-1 (GLP-1). We performed the experiment on diabetic rats to evaluate the effects and mechanisms of ileal transposition on the glycemic metabolism. Methods Twenty Goto-Kakizaki (GK) rats were randomly divided into the ileal transposition group (IT group) and the sham operation group (Sham group). Weight, food intake, fasting plasma glucose (FPG), fasting insulin (F-ins), oral glucose tolerance test (OGTT) and GLP-1 were determined at baseline and 1, 4, 8, 16 and 24 weeks post-operatively. The homeostasis model assessment-insulin resistance (HOMA-IR) index and the area under the curve (AUC) during OGTT were measured. Histological determination of the GLP-1 receptor (GLP-1R) was performed on the pancreas and ileum 24 weeks post-operatively. Results In comparison with the Sham group, the IT group showed a higher GLP-1 level and lower AUC at 4, 8, 16 and 24 weeks post-operatively (all P < 0.05) and a lower FPG, F-ins levels and HOMA-IR at 8, 16 and 24 weeks post-operatively (all P < 0.05). Compared with baseline levels, the plasma GLP-1, AUC and FPG levels decreased significantly at each post-operative time point in the IT group (all P < 0.05), but not in the Sham group (all P > 0.05); F-ins and HOMA-IR significantly decreased at 8, 16 and 24 weeks post-operatively in the IT group (all P < 0.05). GLP-1R expression in the IT group was significantly higher than that of the Sham group in both the pancreas and the ileum at 24 weeks post-operatively (P < 0.05). Conclusions Ileal transposition ameliorated glucose metabolism without reduction in weight or food intake in GK rats, which may be induced by the increased GLP-1 expression. However, the delayed improvement of insulin resistance, accompanied by decreased plasma insulin levels, might not directly result from the increased GLP-1.
Collapse
Affiliation(s)
- Hengliang Zhu
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China.,Department of Gastrointestinal Surgery, The Seventh Affiliated Hospital, Sun Yat-sen University, Shenzhen, Guangdong, China
| | - Huaiming Wang
- Department of Colorectal Surgery, The Sixth Affiliated Hospital, Sun Yat-sen University, Guangzhou, Guangdong, China
| | - Zhihai Zheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Bailiang Ye
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaojiao Ruan
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xiaofeng Zheng
- Department of Gastrointestinal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Guoxin Li
- Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| |
Collapse
|
|
23
|
Wei M, Shao Y, Liu QR, Wu QZ, Zhang X, Zhong MW, Liu SZ, Zhang GY, Hu SY. Bile acid profiles within the enterohepatic circulation in a diabetic rat model after bariatric surgeries. Am J Physiol Gastrointest Liver Physiol 2018; 314:G537-G546. [PMID: 29351394 DOI: 10.1152/ajpgi.00311.2017] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Bile acids (BAs), which are synthesized in the liver and cycled in the enterohepatic circulation, have been recognized as signaling molecules by activating their receptors in the intestine and liver. Serum taurine-conjugated BAs have been shown to be elevated after bariatric surgeries although the postoperative BA profiles within the enterohepatic circulation have not been investigated. Clarification of these profiles could help explain the mechanisms by which bariatric surgery leads to BA profile alterations and subsequent metabolic effects. We performed duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham procedures in an obese diabetic rat model induced by high-fat diet and streptozotocin. The weight loss and antidiabetic effects were evaluated postsurgery. BA profiles in the systemic serum and within the enterohepatic circulation were analyzed, together with the expression of related BA transporters and enzymes at week 12 after surgery. Compared with sham, SG induced sustained weight loss, and both DJB and SG significantly improved glucose tolerance and insulin sensitivity with enhanced glucagon-like peptide 1 secretion. Similar to changes in the serum, BAs, especially taurine-conjugated species, were also elevated in the enterohepatic circulation (bile and portal vein) after DJB and SG. In addition, the expression of key BA transporters and conjugational enzymes was elevated postoperatively, whereas the enzymes responsible for BA synthesis were decreased. In conclusion, DJB and SG elevated BA levels in the systemic serum and enterohepatic circulation, especially taurine-conjugated species, which likely indicates increased ileal reabsorption and hepatic conjugation rather than synthesis. NEW & NOTEWORTHY Bile acids (BAs) have been implicated as potential mediators of the weight-independent effects of bariatric surgery. For the first time, we discovered that duodenal-jejunal bypass and sleeve gastrectomy elevated BAs, particularly the taurine-conjugated species in the enterohepatic circulation, likely through the promotion of ileal reabsorption and hepatic conjugation rather than BA synthesis. These findings will improve our understanding of BA metabolism after bariatric surgery and their subsequent metabolic effects.
Collapse
Affiliation(s)
- Meng Wei
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Yi Shao
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Qiao-Ran Liu
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Qun-Zheng Wu
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Xiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Ming-Wei Zhong
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Shao-Zhuang Liu
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - Guang-Yong Zhang
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| | - San-Yuan Hu
- Department of General Surgery, Qilu Hospital of Shandong University , Jinan , People's Republic of China
| |
Collapse
|
|
24
|
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.
Collapse
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.
| |
Collapse
|
|
25
|
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.
Collapse
|
|
26
|
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.
Collapse
|
|
27
|
Guo Y, Huang ZP, Liu CQ, Qi L, Sheng Y, Zou DJ. Modulation of the gut microbiome: a systematic review of the effect of bariatric surgery. Eur J Endocrinol 2018; 178:43-56. [PMID: 28916564 DOI: 10.1530/eje-17-0403] [Citation(s) in RCA: 128] [Impact Index Per Article: 18.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2017] [Revised: 08/14/2017] [Accepted: 09/15/2017] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Bariatric surgery is recommended for patients with obesity and type 2 diabetes. Recent evidence suggested a strong connection between gut microbiota and bariatric surgery. DESIGN Systematic review. METHODS The PubMed and OVID EMBASE were used, and articles concerning bariatric surgery and gut microbiota were screened. The main outcome measures were alterations of gut microbiota after bariatric surgery and correlations between gut microbiota and host metabolism. We applied the system of evidence level to evaluate the alteration of microbiota. Modulation of short-chain fatty acid and gut genetic content was also investigated. RESULTS Totally 12 animal experiments and 9 clinical studies were included. Based on strong evidence, 4 phyla (Bacteroidetes, Fusobacteria, Verrucomicrobia and Proteobacteria) increased after surgery; within the phylum Firmicutes, Lactobacillales and Enterococcus increased; and within the phylum Proteobacteria, Gammaproteobacteria, Enterobacteriales Enterobacteriaceae and several genera and species increased. Decreased microbial groups were Firmicutes, Clostridiales, Clostridiaceae, Blautia and Dorea. However, the change in microbial diversity is still under debate. Faecalibacterium prausnitzii, Lactobacillus and Coprococcus comes are implicated in many of the outcomes, including body composition and glucose homeostasis. CONCLUSIONS There is strong evidence to support a considerable alteration of the gut microbiome after bariatric surgery. Deeper investigations are required to confirm the mechanisms that link the gut microbiome and metabolic alterations in human metabolism.
Collapse
Affiliation(s)
- Yan Guo
- Department of Endocrinology, Changhai Hospital, Shanghai, China
| | - Zhi-Ping Huang
- Third Department of Hepatic Surgery, Shanghai Eastern Hepatobiliary Surgery Hospital, Shanghai, China
- Department of General Surgery, Shangai Changhai Hospital, Shanghai, China
| | - Chao-Qian Liu
- Department of General Surgery, Shangai Changhai Hospital, Shanghai, China
| | - Lin Qi
- Department of Orthopaedics, the Second Xiangya Hospital, Central South University, Changsha, Hunan, China
| | - Yuan Sheng
- Department of General Surgery, Shangai Changhai Hospital, Shanghai, China
| | - Da-Jin Zou
- Department of Endocrinology, Changhai Hospital, Shanghai, China
| |
Collapse
|
|
28
|
Wu Q, Zhang X, Zhong M, Han H, Liu S, Liu T, Wei M, Guo W, Xie H, Hu S, Zhang G. Effects of Bariatric Surgery on Serum Bile Acid Composition and Conjugation in a Diabetic Rat Model. Obes Surg 2017; 26:2384-92. [PMID: 26843082 DOI: 10.1007/s11695-016-2087-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
BACKGROUND Serum bile acids (BAs) are elevated following bariatric surgery and have emerged as a potential glucose-lowering beneficial factor. The change of BA components and its underlying mechanisms may be of great significance during bariatric surgery. The aim of this study is to investigate the effects of different bariatric procedures on serum BA composition and explore the potential mechanisms using a diabetic rat model. METHODS Duodenal-jejunal bypass (DJB), sleeve gastrectomy (SG), and sham operation were performed in diabetic rats induced by high-fat diet (HFD) and streptozotocin (STZ). Body weight, food intake, oral glucose tolerance test (OGTT), and insulin tolerance test (ITT) were measured at indicated time points. Serum BAs composition and the expression of cholesterol 7α hydroxylase (CYP7A1), bile acid: CoA synthase (BACS) and bile acid-CoA: amino acid N-acyltransferase (BAAT) at both transcriptional and protein levels in the liver were evaluated at 12 weeks postoperatively. RESULTS Compared with sham group, DJB and SG both achieved rapid and sustained improvements in glucose tolerance and insulin sensitivity. They also resulted in increased serum BAs, especially the taurine-conjugated BAs by elevated conjugation. No obvious difference was detected between DJB and SG except that SG achieved decreased weight gain and food intake. CONCLUSIONS The preferentially elevated serum taurine-conjugated BAs were similar after different bariatric surgeries, and the enhanced conjugation of BAs in the liver might account for the changed serum BAs profiles.
Collapse
Affiliation(s)
- Qunzheng Wu
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Xiang Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Mingwei Zhong
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Haifeng Han
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Shaozhuang Liu
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Teng Liu
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Meng Wei
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Wei Guo
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Haibin Xie
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Sanyuan Hu
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China
| | - Guangyong Zhang
- Department of General Surgery, Qilu Hospital of Shandong University, 107# Wenhua Xi Road, Jinan, 250012, Shandong, People's Republic of China.
| |
Collapse
|
|
29
|
McGavigan AK, Garibay D, Henseler ZM, Chen J, Bettaieb A, Haj FG, Ley RE, Chouinard ML, Cummings BP. TGR5 contributes to glucoregulatory improvements after vertical sleeve gastrectomy in mice. Gut 2017; 66:226-234. [PMID: 26511794 PMCID: PMC5512436 DOI: 10.1136/gutjnl-2015-309871] [Citation(s) in RCA: 159] [Impact Index Per Article: 19.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/30/2015] [Revised: 09/29/2015] [Accepted: 09/30/2015] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Vertical sleeve gastrectomy (VSG) produces high rates of type 2 diabetes remission; however, the mechanisms responsible remain incompletely defined. VSG increases circulating bile acid concentrations and bile acid signalling through TGR5 improves glucose homeostasis. Therefore, we investigated the role of TGR5 signalling in mediating the glucoregulatory benefits of VSG. DESIGN VSG or sham surgery was performed in high-fat-fed male Tgr5+/+ (wild type) and Tgr5-/- (knockout) littermates. Sham-operated mice were fed ad libitum or food restricted to match their body weight to VSG-operated mice. Body weight, food intake, energy expenditure, insulin signalling and circulating bile acid profiles were measured and oral glucose tolerance testing, islet immunohistochemistry and gut microbial profiling were performed. RESULTS VSG decreased food intake and body weight, increased energy expenditure and circulating bile acid concentrations, improved fasting glycaemia, glucose tolerance and glucose-stimulated insulin secretion, enhanced nutrient-stimulated glucagon-like peptide 1 secretion and produced favourable shifts in gut microbial populations in both genotypes. However, the body weight-independent improvements in fasting glycaemia, glucose tolerance, hepatic insulin signalling, hepatic inflammation and islet morphology after VSG were attenuated in Tgr5-/- relative to Tgr5+/+ mice. Furthermore, VSG produced metabolically favourable alterations in circulating bile acid profiles that were blunted in Tgr5-/- relative to Tgr5+/+ mice. TGR5-dependent regulation of hepatic Cyp8b1 expression may have contributed to TGR5-mediated shifts in the circulating bile acid pool after VSG. CONCLUSIONS These results suggest that TGR5 contributes to the glucoregulatory benefits of VSG surgery by promoting metabolically favourable shifts in the circulating bile acid pool.
Collapse
Affiliation(s)
- Anne K McGavigan
- Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Darline Garibay
- Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Zachariah M Henseler
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA
- Department of Microbiology, Cornell University, Ithaca, New York, USA
| | - Jack Chen
- Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| | - Ahmed Bettaieb
- Department of Nutrition, University of California, Davis, Davis, California, USA
| | - Fawaz G Haj
- Department of Nutrition, University of California, Davis, Davis, California, USA
| | - Ruth E Ley
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, New York, USA
- Department of Microbiology, Cornell University, Ithaca, New York, USA
| | - Michael L Chouinard
- Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Indianapolis, Indiana, USA
| | - Bethany P Cummings
- Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, New York, USA
| |
Collapse
|
|
30
|
Duodenal endoluminal barrier sleeve alters gut microbiota of ZDF rats. Int J Obes (Lond) 2016; 41:381-389. [PMID: 27924082 PMCID: PMC5340580 DOI: 10.1038/ijo.2016.224] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2016] [Revised: 10/13/2016] [Accepted: 10/30/2016] [Indexed: 12/13/2022]
Abstract
BACKGROUND/OBJECTIVES The combination of energy dense diets and reduced energy expenditure in modern society has escalated the prevalence of obesity and obesity-related comorbidities. Among these disease states, type-2 diabetics (T2D) are disproportionately associated with obesity, suggesting a shared etiology. In conjunction with defects in hormonal and inflammatory states, obesity and T2D are also characterized by dysbiosis. METHODS We have recently described the beneficial effects of duodenal nutrient exclusion, as induced by the duodenal endoluminal sleeve (DES); including body weight loss, prevented fat mass accumulation, and improved glucose tolerance in the ZDF rat, a rodent model of obesity and type-2 diabetes (T2D). To assess the relative role of DES on hindgut microbiota in the context of these metabolic changes, we analyzed cecal samples from rats implanted with a duodenal endoluminal sleeve (DES), or a sham control of this procedure. A group of pair-fed (pf) sham controls was also included to account for changes induced by reduced body weight and food intake. RESULTS Analysis of hindgut microbiota following DES in the ZDF rat elucidated discrete changes in several microbial populations including a reduction in Paraprevotella family members of the Clostridiales order along with an increase in Akkermansia muciniphila and species of the Allobaculum and Bifidobacterium genera. CONCLUSIONS Altogether, these observations suggest that like Roux-en Y gastric bypass (RYGB) and Metformin, regulation of gut microbiota may be a contributing factor to the therapeutic effects of DES.
Collapse
|
|
31
|
Kim T, Holleman CL, Ptacek T, Morrow CD, Habegger KM. Duodenal endoluminal barrier sleeve alters gut microbiota of ZDF rats. Parasite Immunol 2016; 39. [PMID: 27924082 DOI: 10.1111/pim.12404] [Citation(s) in RCA: 43] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2016] [Accepted: 11/24/2016] [Indexed: 12/31/2022]
Abstract
BACKGROUND/OBJECTIVES The combination of energy dense diets and reduced energy expenditure in modern society has escalated the prevalence of obesity and obesity-related comorbidities. Among these disease states, type-2 diabetics (T2D) are disproportionately associated with obesity, suggesting a shared etiology. In conjunction with defects in hormonal and inflammatory states, obesity and T2D are also characterized by dysbiosis. METHODS We have recently described the beneficial effects of duodenal nutrient exclusion, as induced by the duodenal endoluminal sleeve (DES); including body weight loss, prevented fat mass accumulation, and improved glucose tolerance in the ZDF rat, a rodent model of obesity and type-2 diabetes (T2D). To assess the relative role of DES on hindgut microbiota in the context of these metabolic changes, we analyzed cecal samples from rats implanted with a duodenal endoluminal sleeve (DES), or a sham control of this procedure. A group of pair-fed (pf) sham controls was also included to account for changes induced by reduced body weight and food intake. RESULTS Analysis of hindgut microbiota following DES in the ZDF rat elucidated discrete changes in several microbial populations including a reduction in Paraprevotella family members of the Clostridiales order along with an increase in Akkermansia muciniphila and species of the Allobaculum and Bifidobacterium genera. CONCLUSIONS Altogether, these observations suggest that like Roux-en Y gastric bypass (RYGB) and Metformin, regulation of gut microbiota may be a contributing factor to the therapeutic effects of DES.
Collapse
Affiliation(s)
- T Kim
- Comprehensive Diabetes Center and Department of Medicine-Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA
| | - C L Holleman
- Comprehensive Diabetes Center and Department of Medicine-Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA
| | - T Ptacek
- Center for Clinical and Translational Sciences, University of Alabama at Birmingham, Birmingham, AL, USA.,Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - C D Morrow
- Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL, USA.,Department of Cell Developmental and Integrative Biology, University of Alabama at Birmingham, Birmingham, AL, USA
| | - K M Habegger
- Comprehensive Diabetes Center and Department of Medicine-Endocrinology, Diabetes and Metabolism, University of Alabama at Birmingham, Birmingham, AL, USA
| |
Collapse
|
|
32
|
Kaska L, Sledzinski T, Chomiczewska A, Dettlaff-Pokora A, Swierczynski J. Improved glucose metabolism following bariatric surgery is associated with increased circulating bile acid concentrations and remodeling of the gut microbiome. World J Gastroenterol 2016; 22:8698-8719. [PMID: 27818587 PMCID: PMC5075546 DOI: 10.3748/wjg.v22.i39.8698] [Citation(s) in RCA: 75] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2016] [Revised: 08/23/2016] [Accepted: 09/14/2016] [Indexed: 02/06/2023] Open
Abstract
Clinical studies have indicated that circulating bile acid (BA) concentrations increase following bariatric surgery, especially following malabsorptive procedures such as Roux-en-Y gastric bypasses (RYGB). Moreover, total circulating BA concentrations in patients following RYGB are positively correlated with serum glucagon-like peptide-1 concentrations and inversely correlated with postprandial glucose concentrations. Overall, these data suggest that the increased circulating BA concentrations following bariatric surgery - independently of calorie restriction and body-weight loss - could contribute, at least in part, to improvements in insulin sensitivity, incretin hormone secretion, and postprandial glycemia, leading to the remission of type-2 diabetes (T2DM). In humans, the primary and secondary BA pool size is dependent on the rate of biosynthesis and the enterohepatic circulation of BAs, as well as on the gut microbiota, which play a crucial role in BA biotransformation. Moreover, BAs and gut microbiota are closely integrated and affect each other. Thus, the alterations in bile flow that result from anatomical changes caused by bariatric surgery and changes in gut microbiome may influence circulating BA concentrations and could subsequently contribute to T2DM remission following RYGB. Research data coming largely from animal and cell culture models suggest that BAs can contribute, via nuclear farnezoid X receptor (FXR) and membrane G-protein-receptor (TGR-5), to beneficial effects on glucose metabolism. It is therefore likely that FXR, TGR-5, and BAs play a similar role in glucose metabolism following bariatric surgery in humans. The objective of this review is to discuss in detail the results of published studies that show how bariatric surgery affects glucose metabolism and subsequently T2DM remission.
Collapse
|
|
33
|
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.
Collapse
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
| |
Collapse
|
|
34
|
Duodenal-jejunal bypass changes the composition of the gut microbiota. Surg Today 2016; 47:137-140. [PMID: 27412617 DOI: 10.1007/s00595-016-1373-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Accepted: 04/19/2016] [Indexed: 01/14/2023]
|
|
35
|
Expedited Biliopancreatic Juice Flow to the Distal Gut Benefits the Diabetes Control After Duodenal-Jejunal Bypass. Obes Surg 2016; 25:1802-9. [PMID: 25726319 DOI: 10.1007/s11695-015-1633-7] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
BACKGROUND Serum bile acids (BAs) are elevated after metabolic surgeries including Roux-en-Y gastric bypass (RYGB), ileal transposition (IT), and duodenal-jejunal bypass (DJB). Recently, BAs have emerged as a kind of signaling molecules, which can not only promote glucagon-like peptide-1 (GLP-1) secretion but can also regulate multiple enzymes involved in glucose metabolism. The aim of this study was to investigate whether expedited biliopancreatic juice flow to the distal gut contributes to the increased serum GLP-1 and BAs and benefits the diabetes control after DJB. METHODS DJB, long alimentary limb DJB (LDJB), duodenal-jejunal anastomosis (DJA), and sham operation were performed in diabetic rats induced by high-fat diet (HFD) and low dose of streptozotocin (STZ). Body weight, food intake, oral glucose tolerance, insulin tolerance, glucose-stimulated insulin and GLP-1 secretion, fasting serum total bile acids (TBAs), and lipid profiles were measured at indicated time points. RESULTS Compared with sham operation, DJA, DJB, and LDJB all achieved rapid and dramatic improvements in glucose tolerance and insulin sensitivity independently of food restriction and weight loss. DJB and LDJB-operated rats exhibited even better glucose tolerance, higher fasting serum TBAs, and higher glucose-stimulated GLP-1 secretion than the DJA group postoperatively. No difference was detected in insulin sensitivity and glucose-stimulated insulin secretion between DJA, DJB, and LDJB groups. CONCLUSIONS Expedited biliopancreatic juice flow to the distal gut was associated with augmented GLP-1 secretion and increased fasting serum TBA concentration, which may partly explain the metabolic benefits of DJB.
Collapse
|
|
36
|
Zietek T, Rath E. Inflammation Meets Metabolic Disease: Gut Feeling Mediated by GLP-1. Front Immunol 2016; 7:154. [PMID: 27148273 PMCID: PMC4840214 DOI: 10.3389/fimmu.2016.00154] [Citation(s) in RCA: 90] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2016] [Accepted: 04/08/2016] [Indexed: 12/14/2022] Open
Abstract
Chronic diseases, such as obesity and diabetes, cardiovascular, and inflammatory bowel diseases (IBD) share common features in their pathology. Metabolic disorders exhibit strong inflammatory underpinnings and vice versa, inflammation is associated with metabolic alterations. Next to cytokines and cellular stress pathways, such as the unfolded protein response (UPR), alterations in the enteroendocrine system are intersections of various pathologies. Enteroendocrine cells (EEC) have been studied extensively for their ability to regulate gastrointestinal motility, secretion, and insulin release by release of peptide hormones. In particular, the L-cell-derived incretin hormone glucagon-like peptide 1 (GLP-1) has gained enormous attention due to its insulinotropic action and relevance in the treatment of type 2 diabetes (T2D). Yet, accumulating data indicate a critical role for EEC and in particular for GLP-1 in metabolic adaptation and in orchestrating immune responses beyond blood glucose control. EEC sense the lamina propria and luminal environment, including the microbiota via receptors and transporters. Subsequently, mediating signals by secreting hormones and cytokines, EEC can be considered as integrators of metabolic and inflammatory signaling. This review focuses on L cell and GLP-1 functions in the context of metabolic and inflammatory diseases. The effects of incretin-based therapies on metabolism and immune system are discussed and the interrelation and common features of metabolic and immune-mediated disorders are highlighted. Moreover, it presents data on the impact of inflammation, in particular of IBD on EEC and discusses the potential role of the microbiota as link between nutrients, metabolism, immunity, and disease.
Collapse
Affiliation(s)
- Tamara Zietek
- Department of Nutritional Physiology, Technische Universität München , Freising , Germany
| | - Eva Rath
- Chair of Nutrition and Immunology, Technische Universität München , Freising , Germany
| |
Collapse
|
|
37
|
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.
Collapse
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
| |
Collapse
|
|
38
|
Duodenal-Jejunal Bypass Preferentially Elevates Serum Taurine-Conjugated Bile Acids and Alters Gut Microbiota in a Diabetic Rat Model. Obes Surg 2015; 26:1890-9. [DOI: 10.1007/s11695-015-2031-x] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
|
|
39
|
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.
Collapse
|
|
40
|
Bile diversion to the distal small intestine has comparable metabolic benefits to bariatric surgery. Nat Commun 2015. [PMID: 26197299 PMCID: PMC4518285 DOI: 10.1038/ncomms8715] [Citation(s) in RCA: 152] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Roux-en-Y gastric bypass (RYGB) is highly effective in reversing obesity and associated diabetes. Recent observations in humans suggest a contributing role of increased circulating bile acids in mediating such effects. Here we use a diet-induced obesity (DIO) mouse model and compare metabolic remission when bile flow is diverted through a gallbladder anastomosis to jejunum, ileum or duodenum (sham control). We find that only bile diversion to the ileum results in physiologic changes similar to RYGB, including sustained improvements in weight, glucose tolerance and hepatic steatosis despite differential effects on hepatic gene expression. Circulating free fatty acids and triglycerides decrease while bile acids increase, particularly conjugated tauro-β-muricholic acid, an FXR antagonist. Activity of the hepatic FXR/FGF15 signalling axis is reduced and associated with altered gut microbiota. Thus bile diversion, independent of surgical rearrangement of the gastrointestinal tract, imparts significant weight loss accompanied by improved glucose and lipid homeostasis that are hallmarks of RYGB.
Collapse
|
|
41
|
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.
Collapse
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
| |
Collapse
|
|
42
|
Kowal JM, Haanes KA, Christensen NM, Novak I. Bile acid effects are mediated by ATP release and purinergic signalling in exocrine pancreatic cells. Cell Commun Signal 2015; 13:28. [PMID: 26050734 PMCID: PMC4459444 DOI: 10.1186/s12964-015-0107-9] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2015] [Accepted: 05/26/2015] [Indexed: 02/06/2023] Open
Abstract
Background In many cells, bile acids (BAs) have a multitude of effects, some of which may be mediated by specific receptors such the TGR5 or FXR receptors. In pancreas systemic BAs, as well as intra-ductal BAs from bile reflux, can affect pancreatic secretion. Extracellular ATP and purinergic signalling are other important regulators of similar secretory mechanisms in pancreas. The aim of our study was to elucidate whether there is interplay between ATP and BA signalling. Results Here we show that CDCA (chenodeoxycholic acid) caused fast and concentration-dependent ATP release from acini (AR42J) and duct cells (Capan-1). Taurine and glycine conjugated forms of CDCA had smaller effects on ATP release in Capan-1 cells. In duct monolayers, CDCA stimulated ATP release mainly from the luminal membrane; the releasing mechanisms involved both vesicular and non-vesicular secretion pathways. Duct cells were not depleted of intracellular ATP with CDCA, but acinar cells lost some ATP, as detected by several methods including ATP sensor AT1.03YEMK. In duct cells, CDCA caused reversible increase in the intracellular Ca2+ concentration [Ca2 +]i, which could be significantly inhibited by antagonists of purinergic receptors. The TGR5 receptor, expressed on the luminal side of pancreatic ducts, was not involved in ATP release and Ca2+ signals, but could stimulate Na+/Ca2+ exchange in some conditions. Conclusions CDCA evokes significant ATP release that can stimulate purinergic receptors, which in turn increase [Ca2+]i. The TGR5 receptor is not involved in these processes but can play a protective role at high intracellular Ca2+ conditions. We propose that purinergic signalling could be taken into consideration in other cells/organs, and thereby potentially explain some of the multifaceted effects of BAs. Electronic supplementary material The online version of this article (doi:10.1186/s12964-015-0107-9) contains supplementary material, which is available to authorized users.
Collapse
Affiliation(s)
- Justyna M Kowal
- Department of Biology, Section for Cell Biology and Physiology, August Krogh Building, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark.
| | - Kristian A Haanes
- Department of Biology, Section for Cell Biology and Physiology, August Krogh Building, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark. .,Present address: Department of Clinical Experimental Research, Glostrup Research Institute, Copenhagen University Hospital, Glostrup, Denmark.
| | - Nynne M Christensen
- Department of Biology, Section for Cell Biology and Physiology, August Krogh Building, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark.
| | - Ivana Novak
- Department of Biology, Section for Cell Biology and Physiology, August Krogh Building, University of Copenhagen, Universitetsparken 13, DK-2100, Copenhagen, Denmark.
| |
Collapse
|
|
43
|
Verbeek J, Lannoo M, Pirinen E, Ryu D, Spincemaille P, Vander Elst I, Windmolders P, Thevissen K, Cammue BPA, van Pelt J, Fransis S, Van Eyken P, Ceuterick-De Groote C, Van Veldhoven PP, Bedossa P, Nevens F, Auwerx J, Cassiman D. Roux-en-y gastric bypass attenuates hepatic mitochondrial dysfunction in mice with non-alcoholic steatohepatitis. Gut 2015; 64:673-83. [PMID: 24917551 DOI: 10.1136/gutjnl-2014-306748] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
OBJECTIVE No therapy for non-alcoholic steatohepatitis (NASH) has been approved so far. Roux-en-y gastric bypass (RYGB) is emerging as a therapeutic option, although its effect on NASH and related hepatic molecular pathways is unclear from human studies. We studied the effect of RYGB on pre-existent NASH and hepatic mitochondrial dysfunction-a key player in NASH pathogenesis-in a novel diet-induced mouse model nicely mimicking human disease. DESIGN C57BL/6J mice were fed a high-fat high-sucrose diet (HF-HSD). RESULTS HF-HSD led to early obesity, insulin resistance and hypercholesterolaemia. HF-HSD consistently induced NASH (steatosis, hepatocyte ballooning and inflammation) with fibrosis already after 12-week feeding. NASH was accompanied by hepatic mitochondrial dysfunction, characterised by decreased mitochondrial respiratory chain (MRC) complex I and IV activity, ATP depletion, ultrastructural abnormalities, together with higher 4-hydroxynonenal (HNE) levels, increased uncoupling protein 2 (UCP2) and tumour necrosis factor-α (TNF-α) mRNA and free cholesterol accumulation. In our model of NASH and acquired mitochondrial dysfunction, RYGB induced sustained weight loss, improved insulin resistance and inhibited progression of NASH, with a marked reversal of fibrosis. In parallel, RYGB preserved hepatic MRC complex I activity, restored ATP levels, limited HNE production and decreased TNF-α mRNA. CONCLUSIONS Progression of NASH and NASH-related hepatic mitochondrial dysfunction can be prevented by RYGB. RYGB preserves respiratory chain complex activity, thereby restoring energy output, probably by limiting the amount of oxidative stress and TNF-α. These data suggest that modulation of hepatic mitochondrial function contributes to the favourable effect of RYBG on established NASH.
Collapse
Affiliation(s)
- Jef Verbeek
- Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Matthias Lannoo
- Department of Abdominal Surgery, University Hospitals KU Leuven, Leuven, Belgium
| | - Eija Pirinen
- Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland Departments of Biotechnology and Molecular Medicine, A.I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, Kuopio, Finland
| | - Dongryeol Ryu
- Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | | | - Ingrid Vander Elst
- Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Petra Windmolders
- Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Karin Thevissen
- Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Leuven, Belgium
| | - Bruno P A Cammue
- Centre of Microbial and Plant Genetics (CMPG), KU Leuven, Leuven, Belgium Department of Plant Systems Biology, Vlaams Instituut voor Biotechnologie (VIB), Ghent, Belgium
| | - Jos van Pelt
- Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Sabine Fransis
- Department of Pathology, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Peter Van Eyken
- Department of Pathology, Ziekenhuis Oost-Limburg, Genk, Belgium
| | - Chantal Ceuterick-De Groote
- Laboratory of Ultrastructural Neuropathology, Institute Born-Bunge (IBB), University of Antwerp, Antwerp, Belgium
| | - Paul P Van Veldhoven
- Laboratory of Lipid Biochemistry and Protein Interactions, KU Leuven, Leuven, Belgium
| | - Pierre Bedossa
- Department of Pathology, Hopital Beaujon, Clichy, France
| | - Frederik Nevens
- Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium
| | - Johan Auwerx
- Laboratory for Integrative and Systems Physiology, Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland
| | - David Cassiman
- Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium Metabolic Center, University Hospitals KU Leuven, Leuven, Belgium
| |
Collapse
|
|
44
|
Bile acids, obesity, and the metabolic syndrome. Best Pract Res Clin Gastroenterol 2014; 28:573-83. [PMID: 25194176 PMCID: PMC4159616 DOI: 10.1016/j.bpg.2014.07.004] [Citation(s) in RCA: 136] [Impact Index Per Article: 12.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/14/2014] [Revised: 06/30/2014] [Accepted: 07/05/2014] [Indexed: 01/31/2023]
Abstract
Bile acids are increasingly recognized as key regulators of systemic metabolism. While bile acids have long been known to play important and direct roles in nutrient absorption, bile acids also serve as signalling molecules. Bile acid interactions with the nuclear hormone receptor farnesoid X receptor (FXR) and the membrane receptor G-protein-coupled bile acid receptor 5 (TGR5) can regulate incretin hormone and fibroblast growth factor 19 (FGF19) secretion, cholesterol metabolism, and systemic energy expenditure. Bile acid levels and distribution are altered in type 2 diabetes and increased following bariatric procedures, in parallel with reduced body weight and improved insulin sensitivity and glycaemic control. Thus, modulation of bile acid levels and signalling, using bile acid binding resins, TGR5 agonists, and FXR agonists, may serve as a potent therapeutic approach for the treatment of obesity, type 2 diabetes, and other components of the metabolic syndrome in humans.
Collapse
|
|
45
|
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.
Collapse
|
|
46
|
Mid to distal small bowel resection with the preservation of the terminal ileum improves glucose homeostasis in diabetic rats by activating the hindgut-dependent mechanism. J Gastrointest Surg 2014; 18:1186-93. [PMID: 24687254 DOI: 10.1007/s11605-014-2507-3] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/17/2013] [Accepted: 03/16/2014] [Indexed: 01/31/2023]
Abstract
BACKGROUND The aim of this study was to develop a novel surgical model to test the "hindgut hypothesis" and thereby study the role of the gut in glucose homeostasis and the mechanism of action of bariatric surgery. METHOD Sprague-Dawley rats were given a high-fat and high-sugar diet and treated with 25 mg/kg streptozotocin (STZ). The fat-sugar-fed/STZ-treated rats were randomized into mid to distal small bowel resection with the preservation of the terminal ileum (DBRPI) and sham operation (which had a formal celiotomy with bowel manipulation only) groups. Rats were observed for 12 weeks after the operation. The main outcome measures were weight, food intake, non-fasting glucose, an oral glucose tolerance test (OGTT), an insulin tolerance test (ITT), the levels of fasting and glucose-induced insulin, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), serum bile acids, and lipid profile. RESULT The DBRPI and sham groups exhibited no difference in weight and food intake after surgery. When compared to the sham controls, the DBRPI group displayed an improvement in non-fasting glucose, oral glucose tolerance, and insulin tolerance at 4 and 12 weeks postresection. DBRPI elicited an increased serum insulin, PYY and GLP-1 levels at 12 weeks postoperation; furthermore, DBRPI resulted in higher serum levels of triglyceride, total bile acids, total bilirubin, and direct bilirubin levels and lower free fatty acid level at 12 weeks. CONCLUSIONS This study provides strong evidences for the key role of hindgut in the amelioration of diabetes after bariatric surgery. Moreover, these findings confirm that DBRPI is a simple and effective surgical model for testing the "hindgut hypothesis" and focused study of biliary enterohepatic recycling in the context of bariatric operations.
Collapse
|
|
47
|
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.
Collapse
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
| | | |
Collapse
|
|
48
|
Duan J, Zhou J, Tan C, Yuan L. Distal small bowel resection with the preservation of the terminal ileum: a novel model to study the role of the gut in glucose homeostasis. Obes Surg 2014; 24:435-6. [PMID: 24390776 DOI: 10.1007/s11695-013-1168-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
Affiliation(s)
- Jinyuan Duan
- Department of Geriatric Surgery, The Second Xiangya Hospital, Central South University, No.139 Middle Renmin Road, Changsha, Hunan, 410011, People's Republic of China,
| | | | | | | |
Collapse
|
|
49
|
Ramzy AR, Nausheen S, Chelikani PK. Ileal transposition surgery produces ileal length-dependent changes in food intake, body weight, gut hormones and glucose metabolism in rats. Int J Obes (Lond) 2013; 38:379-87. [PMID: 24166069 DOI: 10.1038/ijo.2013.201] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2013] [Revised: 09/23/2013] [Accepted: 10/06/2013] [Indexed: 01/02/2023]
Abstract
BACKGROUND Enhanced stimulation of the lower gut is hypothesized to play a key role in the weight loss and resolution of diabetes following bariatric surgeries. Ileal transposition (IT) permits study of the effects of direct lower gut stimulation on body weight, glucose homeostasis and other metabolic adaptations without the confounds of gastric restriction or foregut exclusion. However, the underlying mechanisms and the length of the ileum sufficient to produce metabolic benefits following IT surgery remain largely unknown. OBJECTIVE To determine the effects of transposing varying lengths of the ileum to upper jejunum on food intake, body weight, glucose tolerance and lower gut hormones, and the expression of key markers of glucose and lipid metabolism in skeletal muscle and adipose tissue in rats. METHODS Adult male Sprague-Dawley rats (n=9/group) were subjected to IT surgery with translocation of 5, 10 or 20 cm of the ileal segment to proximal jejunum or sham manipulations. Daily food intake and body weight were recorded, and an intraperitoneal glucose tolerance test was performed. Blood samples were assayed for hormones and tissue samples for mRNA (RT-qPCR) and/or protein abundance (immunoblotting) of regulatory metabolic markers. RESULTS We demonstrate that IT surgery exerts ileal length-dependent effects on multiple parameters including: (1) decreased food intake and weight gain, (2) improved glucose tolerance, (3) increased tissue expression and plasma concentrations of glucagon-like peptide-1 (GLP-1) and peptide YY (PYY), and decreased leptin concentrations and (4) upregulation of key markers of glucose metabolism (glucose transporter-4 (GLUT-4), insulin receptor substrate 1 (IRS-1), adenosine monophosphate-activated protein kinase (AMPK), hexokinase (HK) and phosphofructokinase (PFK)) together with a downregulation of lipogenic markers (fatty acid synthase (FAS)) in muscle and adipose tissue. CONCLUSIONS Together, our data demonstrate that the reduction in food intake and weight gain, increase in lower gut hormones, glycemic improvements and associated changes in tissue metabolic markers following IT surgery are dependent on the length of the transposed ileum.
Collapse
Affiliation(s)
- A R Ramzy
- Department of Production Animal Health, Faculty of Veterinary Medicine, Alberta, Calgary, Canada
| | - S Nausheen
- Department of Production Animal Health, Faculty of Veterinary Medicine, Alberta, Calgary, Canada
| | - P K Chelikani
- 1] Department of Production Animal Health, Faculty of Veterinary Medicine, Alberta, Calgary, Canada [2] Gastrointestinal Research Group, Calvin, Phoebe and Joan Snyder Institute for Chronic Diseases, University of Calgary, Alberta, Calgary, Canada
| |
Collapse
|