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Abstract
Obesity is a multi-factorial disease that is influenced by genetic, epigenetic, and environmental factors. Precision medicine is a practice wherein prevention and treatment strategies take individual variability into account. It involves using a variety of factors including deep phenotyping using clinical, physiologic, and behavioral characteristics, 'omics assays (eg, genomics, epigenomics, transcriptomics, and microbiomics among others), and environmental factors to devise practices that are individualized to subsets of patients. Personalizing the therapeutic modality to the individual can lead to enhanced effectiveness and tolerability. The authors review advances in precision medicine made in the field of bariatrics and discuss future avenues and challenges.
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Affiliation(s)
- Khushboo Gala
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55902, USA. https://twitter.com/KhushbooSGala
| | - Wissam Ghusn
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55902, USA; Department of Internal Medicine, Boston University Medical Center, Harrison Avenue, Boston, MA 02111, USA. https://twitter.com/Wissam_Ghusn
| | - Andres Acosta
- Precision Medicine for Obesity Program, Division of Gastroenterology and Hepatology, Department of Medicine, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55902, USA.
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Bagheri M, Tanriverdi K, Iafrati MD, Mosley JD, Freedman JE, Ferguson JF. Characterization of the plasma metabolome and lipidome in response to sleeve gastrectomy and gastric bypass surgeries reveals molecular patterns of surgical weight loss. Metabolism 2024; 158:155955. [PMID: 38906372 PMCID: PMC11755375 DOI: 10.1016/j.metabol.2024.155955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2024] [Revised: 05/23/2024] [Accepted: 06/13/2024] [Indexed: 06/23/2024]
Abstract
OBJECTIVES Bariatric surgery improves metabolic health, but the underlying mechanisms are not fully understood. We analyzed the effects of two types of bariatric surgery, sleeve gastrectomy (SG) and Roux-en-Y gastric bypass (RYGB), on the plasma metabolome and lipidome. METHODS We characterized the plasma metabolome (1268 metabolites) and lipidome (953 lipids) pre-operatively and at 3 and 12 months post-operatively in 104 obese adults who were previously recruited to a prospective cohort of bariatric surgery. The metabolomic and lipidomic responses to bariatric surgery over time were analyzed using multivariable linear mixed-effects models. RESULTS There were significant changes in multiple metabolites and lipids, including rapid early changes in amino acid and peptide metabolites, including decreases in branched-chain amino acids (BCAAs), aromatic AAs, alanine and aspartate, and increases in glycine, serine, arginine and citrulline. There were also significant decreases in many triglyceride species, with increases in phosphatidylcholines and phosphatidylethanolamines. There were significant changes in metabolites related to energy metabolism that were apparent only after 12 months. We observed differences by bariatric surgery type in the changes in a small number of primary and secondary bile acids, including glycohyocholate and glyco-beta-muricholate. CONCLUSIONS Our findings highlight the comprehensive changes in metabolites and lipids that occur over the 12 months following bariatric surgery. While both SG and RYGB caused profound changes in the metabolome and lipidome, RYGB was characterized by greater increases in bile acids following surgery.
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Affiliation(s)
- Minoo Bagheri
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America
| | - Kahraman Tanriverdi
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America
| | - Mark D Iafrati
- Department of Vascular Surgery, Vanderbilt University Medical Center, United States of America
| | - Jonathan D Mosley
- Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, United States of America; Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America
| | - Jane E Freedman
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America
| | - Jane F Ferguson
- Division of Cardiovascular Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, United States of America.
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Wang L, Li S, Jiang T. Effects of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy on gut microbiota and glucose metabolism in rats with type 2 diabetes. Front Microbiol 2024; 15:1357749. [PMID: 38863754 PMCID: PMC11165999 DOI: 10.3389/fmicb.2024.1357749] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 05/07/2024] [Indexed: 06/13/2024] Open
Abstract
Background Bariatric and metabolic surgery often leads to significant changes in gut microbiota composition, indicating that changes in gut microbiota after bariatric and metabolic surgery might play a role in ameliorating type 2 diabetes (T2D). However, the effects of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) on gut microbiota in T2D remain unclear. Objectives To investigate the effects of SADI-S on gut microbiota and glucose metabolism in T2D rats. Methods Nineteen T2D rats were randomly divided into the SADI-S group (n = 10) and the sham operation with pair-feeding group (sham-PF, n = 9). Fecal samples were collected to analyze the gut microbiota composition with 16S ribosomal DNA gene sequencing. The fasting blood glucose and glycated hemoglobin were measured to evaluate the effects of SADI-S on glucose metabolism. Results The Chao and ACE index results indicated the richness of the gut microbial community. The ACE and Chao index values were significantly lower in the SADI-S group than in the sham-PF group, indicating that indicating that species richness was significantly lower in the SADI-S group than in the sham-PF group (p < 0.05). Shannon and Simpson indices were used to estimate the species diversity of the gut microbiota. Compared with the sham-PF group, the SADI-S group showed significantly lower Shannon index and higher Simpson index values, indicating that the species diversity was significantly lower in the SADI-S group than in the sham-PF group (p < 0.05). At the genus level, SADI-S significantly changed the abundances of 33 bacteria, including the increased anti-inflammatory bacteria (Akkermansia and Bifidobacterium) and decreased pro-inflammatory bacteria (Bacteroides). SADI-S significantly decreased the fasting blood glucose and glycated hemoglobin levels. The blood glucose level of rats was positively correlated with the relative abundances of 12 bacteria, including Bacteroides, and negatively correlated with the relative abundances of seven bacteria, including Bifidobacterium. Conclusion SADI-S significantly altered the gut microbiota composition of T2D rats, including the increased anti-inflammatory bacteria (Akkermansia and Bifidobacterium) and decreased pro-inflammatory bacteria (Bacteroides). The blood glucose level of rats was positively correlated with the abundances of 12 bacteria, including Bacteroides, but negatively correlated with the relative abundance of 7 bacteria, including Bifidobacterium. These alternations in gut microbiota may be the mechanism through which SADI-S improved T2D. More studies should be performed in the future to validate these effects.
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Affiliation(s)
- Lun Wang
- Department of Gastrointestinal Surgery, Affiliated Hospital of Zunyi Medical University, Zunyi, China
| | - Shixing Li
- Department of Bariatric and Metabolic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
| | - Tao Jiang
- Department of Bariatric and Metabolic Surgery, China-Japan Union Hospital of Jilin University, Changchun, China
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Xu J, Yang XW. LC-MS-Based Metabolomics Reveals the Mechanism of Protection of Berberine against Indomethacin-Induced Gastric Injury in Rats. Molecules 2024; 29:1055. [PMID: 38474567 DOI: 10.3390/molecules29051055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2024] [Revised: 02/23/2024] [Accepted: 02/26/2024] [Indexed: 03/14/2024] Open
Abstract
Berberine is a natural isoquinoline alkaloid with low toxicity, which exists in a wide variety of medicinal plants. Berberine has been demonstrated to exhibit potent prevention of indomethacin-induced gastric injury (GI) but the related mechanism remains unclear. In the present study, liquid chromatography-mass spectrometry (LC-MS)-based metabolomics was applied for the first time to investigate the alteration of serum metabolites in the protection of berberine against indomethacin-induced gastric injury in rats. Subsequently, bioinformatics was utilized to analyze the potential metabolic pathway of the anti-GI effect of berberine. The pharmacodynamic data indicated that berberine could ameliorate gastric pathological damage, inhibit the level of proinflammatory factors in serum, and increase the level of antioxidant factors in serum. The LC-MS-based metabolomics analysis conducted in this study demonstrated the presence of 57 differential metabolites in the serum of rats with induced GI caused by indomethacin, which was associated with 29 metabolic pathways. Moreover, the study revealed that berberine showed a significant impact on the differential metabolites, with 45 differential metabolites being reported between the model group and the group treated with berberine. The differential metabolites were associated with 24 metabolic pathways, and berberine administration regulated 14 of the 57 differential metabolites, affecting 14 of the 29 metabolic pathways. The primary metabolic pathways affected were glutathione metabolism and arachidonic acid metabolism. Based on the results, it can be concluded that berberine has a gastroprotective effect on the GI. This study is particularly significant since it is the first to elucidate the mechanism of berberine's action on GI. The results suggest that berberine's action may be related to energy metabolism, oxidative stress, and inflammation regulation. These findings may pave the way for the development of new therapeutic interventions for the prevention and management of NSAID-induced GI disorders.
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Affiliation(s)
- Jing Xu
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
| | - Xiu-Wei Yang
- State Key Laboratory of Natural and Biomimetic Drugs, Department of Natural Medicines, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
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Chen M, Miao G, Huo Z, Peng H, Wen X, Anton S, Zhang D, Hu G, Brock R, Brantley PJ, Zhao J. Longitudinal Profiling of Fasting Plasma Metabolome in Response to Weight-Loss Interventions in Patients with Morbid Obesity. Metabolites 2024; 14:116. [PMID: 38393008 PMCID: PMC10890440 DOI: 10.3390/metabo14020116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2024] [Revised: 02/02/2024] [Accepted: 02/09/2024] [Indexed: 02/25/2024] Open
Abstract
It is well recognized that patients with severe obesity exhibit remarkable heterogeneity in response to different types of weight-loss interventions. Those who undergo Roux-en-Y gastric bypass (RYGB) usually exhibit more favorable glycemic outcomes than those who receive adjustable gastric banding (BAND) or intensive medical intervention (IMI). The molecular mechanisms behind these observations, however, remain largely unknown. To identify the plasma metabolites associated with differential glycemic outcomes induced by weight-loss intervention, we studied 75 patients with severe obesity (25 each in RYGB, BAND, or IMI). Using untargeted metabolomics, we repeatedly measured 364 metabolites in plasma samples at baseline and 1-year after intervention. Linear regression was used to examine whether baseline metabolites or changes in metabolites are associated with differential glycemic outcomes in response to different types of weight-loss intervention, adjusting for sex, baseline age, and BMI as well as weight loss. Network analyses were performed to identify differential metabolic pathways involved in the observed associations. After correction for multiple testing (q < 0.05), 33 (RYGB vs. IMI) and 28 (RYGB vs. BAND) baseline metabolites were associated with changes in fasting plasma glucose (FPG) or glycated hemoglobin (HbA1c). Longitudinal changes in 38 (RYGB vs. IMI) and 38 metabolites (RYGB vs. BAND) were significantly associated with changes in FPG or HbA1c. The identified metabolites are enriched in pathways involved in the biosynthesis of aminoacyl-tRNA and branched-chain amino acids. Weight-loss intervention evokes extensive changes in plasma metabolites, and the altered metabolome may underlie the differential glycemic outcomes in response to different types of weight-loss intervention, independent of weight loss itself.
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Affiliation(s)
- Mingjing Chen
- Department of Epidemiology, College of Public Health & Health Professions, University of Florida, Gainesville, FL 32603, USA
| | - Guanhong Miao
- Department of Epidemiology, College of Public Health & Health Professions, University of Florida, Gainesville, FL 32603, USA
| | - Zhiguang Huo
- Department of Biostatistics, College of Public Health & Health Professions, University of Florida, Gainesville, FL 32603, USA
| | - Hao Peng
- Department of Epidemiology and Biostatistics, School of Public Health, Medical College, Soochow University, Suzhou 215123, China
| | - Xiaoxiao Wen
- Department of Epidemiology, College of Public Health & Health Professions, University of Florida, Gainesville, FL 32603, USA
| | - Stephen Anton
- Department of Aging and Geriatric Research, University of Florida, Gainesville, FL 32603, USA
| | - Dachuan Zhang
- Department of Biostatistics, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
| | - Gang Hu
- Chronic Disease Epidemiology Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
| | - Ricky Brock
- Behavioral Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
| | - Phillip J Brantley
- Behavioral Medicine Laboratory, Pennington Biomedical Research Center, Louisiana State University System, Baton Rouge, LA 70808, USA
| | - Jinying Zhao
- Department of Epidemiology, College of Public Health & Health Professions, University of Florida, Gainesville, FL 32603, USA
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Demicheva E, Dordiuk V, Polanco Espino F, Ushenin K, Aboushanab S, Shevyrin V, Buhler A, Mukhlynina E, Solovyova O, Danilova I, Kovaleva E. Advances in Mass Spectrometry-Based Blood Metabolomics Profiling for Non-Cancer Diseases: A Comprehensive Review. Metabolites 2024; 14:54. [PMID: 38248857 PMCID: PMC10820779 DOI: 10.3390/metabo14010054] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2023] [Revised: 01/05/2024] [Accepted: 01/12/2024] [Indexed: 01/23/2024] Open
Abstract
Blood metabolomics profiling using mass spectrometry has emerged as a powerful approach for investigating non-cancer diseases and understanding their underlying metabolic alterations. Blood, as a readily accessible physiological fluid, contains a diverse repertoire of metabolites derived from various physiological systems. Mass spectrometry offers a universal and precise analytical platform for the comprehensive analysis of blood metabolites, encompassing proteins, lipids, peptides, glycans, and immunoglobulins. In this comprehensive review, we present an overview of the research landscape in mass spectrometry-based blood metabolomics profiling. While the field of metabolomics research is primarily focused on cancer, this review specifically highlights studies related to non-cancer diseases, aiming to bring attention to valuable research that often remains overshadowed. Employing natural language processing methods, we processed 507 articles to provide insights into the application of metabolomic studies for specific diseases and physiological systems. The review encompasses a wide range of non-cancer diseases, with emphasis on cardiovascular disease, reproductive disease, diabetes, inflammation, and immunodeficiency states. By analyzing blood samples, researchers gain valuable insights into the metabolic perturbations associated with these diseases, potentially leading to the identification of novel biomarkers and the development of personalized therapeutic approaches. Furthermore, we provide a comprehensive overview of various mass spectrometry approaches utilized in blood metabolomics research, including GC-MS, LC-MS, and others discussing their advantages and limitations. To enhance the scope, we propose including recent review articles supporting the applicability of GC×GC-MS for metabolomics-based studies. This addition will contribute to a more exhaustive understanding of the available analytical techniques. The Integration of mass spectrometry-based blood profiling into clinical practice holds promise for improving disease diagnosis, treatment monitoring, and patient outcomes. By unraveling the complex metabolic alterations associated with non-cancer diseases, researchers and healthcare professionals can pave the way for precision medicine and personalized therapeutic interventions. Continuous advancements in mass spectrometry technology and data analysis methods will further enhance the potential of blood metabolomics profiling in non-cancer diseases, facilitating its translation from the laboratory to routine clinical application.
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Affiliation(s)
- Ekaterina Demicheva
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (V.D.); (F.P.E.); (K.U.); (A.B.); (E.M.); (O.S.); (I.D.)
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia
| | - Vladislav Dordiuk
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (V.D.); (F.P.E.); (K.U.); (A.B.); (E.M.); (O.S.); (I.D.)
| | - Fernando Polanco Espino
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (V.D.); (F.P.E.); (K.U.); (A.B.); (E.M.); (O.S.); (I.D.)
| | - Konstantin Ushenin
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (V.D.); (F.P.E.); (K.U.); (A.B.); (E.M.); (O.S.); (I.D.)
- Autonomous Non-Profit Organization Artificial Intelligence Research Institute (AIRI), Moscow 105064, Russia
| | - Saied Aboushanab
- Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620002, Russia; (S.A.); (V.S.); (E.K.)
| | - Vadim Shevyrin
- Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620002, Russia; (S.A.); (V.S.); (E.K.)
| | - Aleksey Buhler
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (V.D.); (F.P.E.); (K.U.); (A.B.); (E.M.); (O.S.); (I.D.)
| | - Elena Mukhlynina
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (V.D.); (F.P.E.); (K.U.); (A.B.); (E.M.); (O.S.); (I.D.)
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia
| | - Olga Solovyova
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (V.D.); (F.P.E.); (K.U.); (A.B.); (E.M.); (O.S.); (I.D.)
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia
| | - Irina Danilova
- Institute of Natural Sciences and Mathematics, Ural Federal University, Ekaterinburg 620075, Russia; (V.D.); (F.P.E.); (K.U.); (A.B.); (E.M.); (O.S.); (I.D.)
- Institute of Immunology and Physiology of the Ural Branch of the Russian Academy of Sciences, Ekaterinburg 620049, Russia
| | - Elena Kovaleva
- Institute of Chemical Engineering, Ural Federal University, Ekaterinburg 620002, Russia; (S.A.); (V.S.); (E.K.)
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Li J, Liu X, Shi Y, Xie Y, Yang J, Du Y, Zhang A, Wu J. Differentiation in TCM patterns of chronic obstructive pulmonary disease by comprehensive metabolomic and lipidomic characterization. Front Immunol 2023; 14:1208480. [PMID: 37492573 PMCID: PMC10363632 DOI: 10.3389/fimmu.2023.1208480] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Accepted: 05/22/2023] [Indexed: 07/27/2023] Open
Abstract
Introduction Chronic obstructive pulmonary disease (COPD) is a complex disease involving inflammation, cell senescence, and autoimmunity. Dialectical treatment for COPD with traditional Chinese medicine (TCM) has the advantage of fewer side effects, more effective suppression of inflammation, and improved immune function. However, the biological base of TCM pattern differentiation in COPD remains unclear. Methods Liquid Chromatography-Quadrupole-Orbitrap mass spectrometry (LC-Q-Orbitrap MS/MS) based metabolomics and lipidomics were used to analyze the serum samples from COPD patients of three TCM patterns in Lung Qi Deficiency (n=65), Lung-Kidney Qi Deficiency (n=54), Lung-Spleen Qi Deficiency (n=52), and healthy subjects (n=41). Three cross-comparisons were performed to characterize metabolic markers for different TCM patterns of COPD vs healthy subjects. Results We identified 28, 8, and 16 metabolites with differential abundance between three TCM patterns of COPD vs healthy subjects, respectively, the metabolic markers included cortisol, hypoxanthine, fatty acids, alkyl-/alkenyl-substituted phosphatidylethanolamine, and phosphatidylcholine, etc. Three panels of metabolic biomarkers specific to the above three TCM patterns yielded areas under the receiver operating characteristic curve of 0.992, 0.881, and 0.928, respectively, with sensitivity of 97.1%, 88.6%, and 91.4%, respectively, and specificity of 96.4%, 81.8%, and 83.9%, respectively. Discussion Combining metabolomics and lipidomics can more comprehensively and accurately trace metabolic markers. As a result, the differences in metabolism were proven to underlie different TCM patterns of COPD, which provided evidence to aid our understanding of the biological basis of dialectical treatment, and can also serve as biomarkers for more accurate diagnosis.
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Affiliation(s)
- Jiansheng Li
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Xinguang Liu
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Yanmin Shi
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Yang Xie
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Jianya Yang
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
- Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
| | - Yan Du
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Ang Zhang
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Jinyan Wu
- Co-construction Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases by Henan & Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China
- Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
- Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
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Oteng AB, Liu L. GPCR-mediated effects of fatty acids and bile acids on glucose homeostasis. Front Endocrinol (Lausanne) 2023; 14:1206063. [PMID: 37484954 PMCID: PMC10360933 DOI: 10.3389/fendo.2023.1206063] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Accepted: 06/20/2023] [Indexed: 07/25/2023] Open
Abstract
Fatty acids and glucose are key biomolecules that share several commonalities including serving as energy substrates and as signaling molecules. Fatty acids can be synthesized endogenously from intermediates of glucose catabolism via de-novo lipogenesis. Bile acids are synthesized endogenously in the liver from the biologically important lipid molecule, cholesterol. Evidence abounds that fatty acids and bile acids play direct and indirect roles in systemic glucose homeostasis. The tight control of plasma glucose levels during postprandial and fasted states is principally mediated by two pancreatic hormones, insulin and glucagon. Here, we summarize experimental studies on the endocrine effects of fatty acids and bile acids, with emphasis on their ability to regulate the release of key hormones that regulate glucose metabolism. We categorize the heterogenous family of fatty acids into short chain fatty acids (SCFAs), unsaturated, and saturated fatty acids, and highlight that along with bile acids, these biomolecules regulate glucose homeostasis by serving as endogenous ligands for specific G-protein coupled receptors (GPCRs). Activation of these GPCRs affects the release of incretin hormones by enteroendocrine cells and/or the secretion of insulin, glucagon, and somatostatin by pancreatic islets, all of which regulate systemic glucose homeostasis. We deduce that signaling induced by fatty acids and bile acids is necessary to maintain euglycemia to prevent metabolic diseases such as type-2 diabetes and related metabolic disorders.
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Guf1 overexpression improves pancreatic β cell functions in type 2 diabetes mellitus rats with Roux-en-Y gastric bypass (RYGB) surgery. J Physiol Biochem 2023:10.1007/s13105-023-00952-6. [PMID: 36905457 DOI: 10.1007/s13105-023-00952-6] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/09/2022] [Accepted: 02/20/2023] [Indexed: 03/12/2023]
Abstract
The Roux-en-Y gastric bypass (RYGB) is a one-of-a-kind treatment among contemporary bariatric surgical procedures, and its therapeutic effects for type 2 diabetes mellitus (T2DM) are satisfactory. The present study performed isobaric tags for relative and absolute quantification (iTRAQ) combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis identifying different proteomics between T2DM rats with or without Roux-en-Y gastric bypass (RYGB) surgery, and GTP binding elongation factor GUF1 (Guf1) was first found to be significantly upregulated in rats from the T2DM plus RYGB group. In the cellular lipotoxicity model induced by palmitic acid stimulation of rat pancreatic beta cell line, INS-1, palmitic acid treatment inhibited cell viability, suppressed GSIS, promoted lipid droplet formation, promoted cell apoptosis, and induced mitochondrial membrane potential loss. The effects of palmitic acid on INS-1 cells mentioned above could be partially eliminated by Guf1 overexpression but aggravated by Guf1 knockdown. Last, under palmitic acid treatment, Guf1 overexpression promotes the PI3K/Akt and NF-κB signaling but inhibits the AMPK activation. Guf1 is upregulated in T2DM rats who received RYGB, and Guf1 overexpression improves cell mitochondrial functions, increases cell proliferation, inhibits cell apoptosis, and promotes cell functions in palmitic acid-treated β cells.
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Grzych G, Bernard L, Lestrelin R, Tailleux A, Staels B. [State of the art on the pathophysiology, diagnosis and treatment of non-alcoholic steatohepatitis (NASH)]. ANNALES PHARMACEUTIQUES FRANÇAISES 2023; 81:183-201. [PMID: 36126753 DOI: 10.1016/j.pharma.2022.09.005] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/07/2022] [Accepted: 09/13/2022] [Indexed: 11/15/2022]
Abstract
NAFLD or non-alcoholic fatty liver disease is one of the complications of obesity and diabetes, the prevalence of which is increasing. The causes of the pathology and its development towards its severe form, NASH or non-alcoholic steatohepatitis, are multiple and still poorly understood. Many different pharmacological classes are being tested in clinical trials to treat NASH, but no pharmaceutical treatment is currently on the market. Moreover, the diagnosis of certainty is only possible by liver biopsy and histological analysis, an invasive procedure with high risk for the patient. It is therefore necessary to better understand the natural history of the disease in order to identify therapeutic targets, but also to identify markers for the diagnosis and monitoring of the disease using a blood sample, which will allow an improvement in patient management.
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Affiliation(s)
- G Grzych
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France.
| | - L Bernard
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - R Lestrelin
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - A Tailleux
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
| | - B Staels
- Univ. Lille, Inserm, CHU Lille, Institut Pasteur de Lille, U1011-EGID, Lille, France
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11
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Gao Z, Zhou W, Lv X, Wang X. Metabolomics as a Critical Tool for Studying Clinical Surgery. Crit Rev Anal Chem 2023; 54:2245-2258. [PMID: 36592066 DOI: 10.1080/10408347.2022.2162810] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023]
Abstract
Metabolomics enables the analysis of metabolites within an organism, which offers the closest direct measurement of the physiological activity of the organism, and has advanced efforts to characterize metabolic states, identify biomarkers, and investigate metabolic pathways. A high degree of innovation in analytical techniques has promoted the application of metabolomics, especially in the study of clinical surgery. Metabolomics can be employed as a clinical testing method to maximize therapeutic outcomes, and has been applied in rapid diagnosis of diseases, timely postoperative monitoring, prognostic assessment, and personalized medicine. This review focuses on the use of mass spectrometry and nuclear magnetic resonance-based metabolomics in clinical surgery, including identifying metabolic changes before and after surgery, finding disease-associated biomarkers, and exploring the potential of personalized therapy. Challenges and opportunities of metabolomics in organ transplantation are also discussed, with a particular emphasis on metabolomics in donor organ evaluation and protection, prognostic outcome prediction, as well as postoperative adverse reaction monitoring. In the end, current limitations of metabolomics in clinical surgery and future research directions are presented.
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Affiliation(s)
- Zhenye Gao
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Wenxiu Zhou
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Xiaoyuan Lv
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China
| | - Xin Wang
- School of Pharmacy, Shanghai Jiao Tong University, Shanghai, P. R. China
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12
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Du Y, Wu J, Tian Y, Zhang L, Zhao P, Li J. Serum metabolomics using ultra-high performance liquid chromatography-Q-Exactive tandem mass spectrometry reveals the mechanism of action of exercise training on chronic obstructive pulmonary disease rats. Biomed Chromatogr 2023; 37:e5507. [PMID: 36097398 DOI: 10.1002/bmc.5507] [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: 04/09/2022] [Revised: 08/17/2022] [Accepted: 09/09/2022] [Indexed: 12/15/2022]
Abstract
Exercise training is the cornerstone component of pulmonary rehabilitation, which results in symptom-reducing, psychosocial, and health economic benefits for chronic obstructive pulmonary disease (COPD) patients. However, the potential mechanisms of its action are poorly understood. This study conducted serum metabolomics using ultra-high performance liquid chromatography-Q-Exactive tandem mass spectrometry to determine the metabolic changes in COPD rats, and the effects of exercise training on improvement in COPD were further investigated. Twelve differential metabolites-which are primarily related to tryptophan metabolism, sphingolipid metabolism, glycerophospholipid metabolism, riboflavin metabolism, pantothenate and CoA biosynthesis, and lysine degradation-were identified in relation to COPD. After the intervention of exercise training, the levels of most metabolites were restored, and the changes in five metabolites were statistically significant, which suggested that exercise training provided effective protection against COPD and might play its role by rebalancing disordered metabolism pathways. This work enhanced our comprehension of the protective mechanism of exercise training on COPD.
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Affiliation(s)
- Yan Du
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province and Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China.,Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China.,Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Jing Wu
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province and Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China.,Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
| | - Yange Tian
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province and Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China.,Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China.,Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Lanxi Zhang
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province and Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China.,Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China
| | - Peng Zhao
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province and Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China.,Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China.,Academy of Chinese Medical Sciences, Henan University of Chinese Medicine, Zhengzhou, China
| | - Jiansheng Li
- Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-constructed by Henan Province and Education Ministry of P.R. China, Henan University of Chinese Medicine, Zhengzhou, China.,Henan Key Laboratory of Chinese Medicine for Respiratory Disease, Henan University of Chinese Medicine, Zhengzhou, China.,Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China
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13
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Hierons SJ, Abbas K, Sobczak AIS, Cerone M, Smith TK, Ajjan RA, Stewart AJ. Changes in plasma free fatty acids in obese patients before and after bariatric surgery highlight alterations in lipid metabolism. Sci Rep 2022; 12:15337. [PMID: 36097032 PMCID: PMC9468139 DOI: 10.1038/s41598-022-19657-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2022] [Accepted: 09/01/2022] [Indexed: 11/13/2022] Open
Abstract
Obesity is a complex disease that increases an individual’s risk of developing other diseases and health-related problems. A common feature is dyslipidemia characterized by increased levels of plasma lipids, which include non-esterified fatty acids (NEFAs). The role of NEFAs in obesity-related morbidity is interesting as NEFAs constitute a reservoir of metabolic energy, are principal components of cell membranes and are precursors for signalling molecules. Bariatric surgery promotes sustained weight loss in severely obese patients, reducing the incidence and severity of co-morbidities. In this study we measure changes in circulating NEFA species in plasma samples taken from 25 obese individuals before and 9 months after Roux-en-Y gastric bypass surgery. The mean weight of the cohort reduced by 29.2% from 149.0 ± 25.1 kg pre-surgery to 105.5 ± 19.8 kg post-surgery and the BMI by 28.2% from 51.8 ± 6.3 kg/m2 pre-surgery to 37.2 ± 5.4 kg/m2. Mean glycated haemoglobin (HbA1c) reduced from 6.5 ± 1.3 to 5.5 ± 0.5%, consistent with the intervention leading to improved glycaemic control, particularly in those who were dysglycemic prior to surgery. Total and LDL cholesterol concentrations were markedly reduced following surgery. Concentrations of seven NEFAs were found to decrease 9 months after surgery compared to pre-surgery levels: myristate, palmitoleate, palmitate, linoleate, oleate, stearate and arachidonate. Bariatric surgery led to increased lipogenesis and elongase activity and decreased stearoyl-CoA desaturase 1 activity. This study therefore highlights metabolic changes that take place following gastric bypass surgery in severely obese patients.
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Affiliation(s)
- Stephen J Hierons
- School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK
| | - Kazim Abbas
- Renal Transplant Unit, Manchester Royal Infirmary, Manchester, UK
| | | | - Michela Cerone
- Biomedical Sciences Research Complex, University of St Andrews, St Andrews, KY16 9ST, UK
| | - Terry K Smith
- Biomedical Sciences Research Complex, University of St Andrews, St Andrews, KY16 9ST, UK
| | - Ramzi A Ajjan
- Leeds Institute of Cardiovascular and Metabolic Medicine, University of Leeds, Leeds, UK
| | - Alan J Stewart
- School of Medicine, University of St Andrews, St Andrews, KY16 9TF, UK.
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14
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Bruno J, Verano M, Vanegas SM, Weinshel E, Ren-Fielding C, Lofton H, Fielding G, Schwack B, Chua DL, Wang C, Li H, Alemán JO. Body Weight and Prandial Variation of Plasma Metabolites in Subjects Undergoing Gastric Band-Induced Weight Loss. OBESITY MEDICINE 2022; 33:100434. [PMID: 37216066 PMCID: PMC10195098 DOI: 10.1016/j.obmed.2022.100434] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/24/2023]
Abstract
BACKGROUND Bariatric procedures are safe and effective treatments for obesity, inducing rapid and sustained loss of excess body weight. Laparoscopic adjustable gastric banding (LAGB) is unique among bariatric interventions in that it is a reversible procedure in which normal gastrointestinal anatomy is maintained. Knowledge regarding how LAGB effects change at the metabolite level is limited. OBJECTIVES To delineate the impact of LAGB on fasting and postprandial metabolite responses using targeted metabolomics. SETTING Individuals undergoing LAGB at NYU Langone Medical Center were recruited for a prospective cohort study. METHODS We prospectively analyzed serum samples from 18 subjects at baseline and 2 months after LAGB under fasting conditions and after a 1-hour mixed meal challenge. Plasma samples were analyzed on a reverse-phase liquid chromatography time-of-flight mass spectrometry metabolomics platform. The main outcome measure was their serum metabolite profile. RESULTS We quantitatively detected over 4,000 metabolites and lipids. Metabolite levels were altered in response to surgical and prandial stimuli, and metabolites within the same biochemical class tended to behave similarly in response to either stimulus. Plasma levels of lipid species and ketone bodies were statistically decreased after surgery whereas amino acid levels were affected more by prandial status than surgical condition. CONCLUSIONS Changes in lipid species and ketone bodies postoperatively suggest improvements in the rate and efficiency of fatty acid oxidation and glucose handling after LAGB. Further investigation is necessary to understand how these findings relate to surgical response, including long term weight maintenance, and obesity-related comorbidities such as dysglycemia and cardiovascular disease.
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Affiliation(s)
- Joanne Bruno
- Laboratory of Translational Obesity Research, 435 East 30 St, New York, NY 10016
- Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016
| | - Michael Verano
- Laboratory of Translational Obesity Research, 435 East 30 St, New York, NY 10016
- Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016
| | - Sally M. Vanegas
- Laboratory of Translational Obesity Research, 435 East 30 St, New York, NY 10016
- Department of Population Health and Comprehensive Program in Obesity Research, New York University Grossman School of Medicine, New York, NY 10016
| | - Elizabeth Weinshel
- Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016
| | - Christine Ren-Fielding
- Department of Surgery, New York University Grossman School of Medicine, New York, NY 10016
| | - Holly Lofton
- Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016
- Department of Surgery, New York University Grossman School of Medicine, New York, NY 10016
| | - George Fielding
- Department of Surgery, New York University Grossman School of Medicine, New York, NY 10016
| | - Bradley Schwack
- Department of Surgery, New York University Grossman School of Medicine, New York, NY 10016
| | - Deborah L Chua
- Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016
| | - Chan Wang
- Department of Population Health and Comprehensive Program in Obesity Research, New York University Grossman School of Medicine, New York, NY 10016
| | - Huilin Li
- Department of Population Health and Comprehensive Program in Obesity Research, New York University Grossman School of Medicine, New York, NY 10016
| | - José O. Alemán
- Laboratory of Translational Obesity Research, 435 East 30 St, New York, NY 10016
- Department of Medicine, New York University Grossman School of Medicine, New York, NY 10016
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15
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Abstract
Metabolomics emerged as an important tool to gain insights on how the body responds to therapeutic interventions. Bariatric surgery is the most effective treatment for severe obesity and obesity-related co-morbidities. Our aim was to conduct a systematic review of the available data on metabolomics profiles that characterize patients submitted to different bariatric surgery procedures, which could be useful to predict clinical outcomes including weight loss and type 2 diabetes remission. For that, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - PRISMA guidelines were followed. Data from forty-seven original study reports addressing metabolomics profiles induced by bariatric surgery that met eligibility criteria were compiled and summarized. Amino acids, lipids, energy-related and gut microbiota-related were the metabolite classes most influenced by bariatric surgery. Among these, higher pre-operative levels of specific lipids including phospholipids, long-chain fatty acids and bile acids were associated with post-operative T2D remission. As conclusion, metabolite profiling could become a useful tool to predict long term response to different bariatric surgery procedures, allowing more personalized interventions and improved healthcare resources allocation.
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Affiliation(s)
- Matilde Vaz
- Endocrine & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal
- Department of Anatomy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
| | - Sofia S Pereira
- Endocrine & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal
- Department of Anatomy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal
| | - Mariana P Monteiro
- Endocrine & Metabolic Research, Unit for Multidisciplinary Research in Biomedicine (UMIB), University of Porto, Porto, Portugal.
- Department of Anatomy, School of Medicine and Biomedical Sciences (ICBAS), University of Porto, Porto, Portugal.
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16
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Guo Z, Pan J, Zhu H, Chen ZY. Metabolites of Gut Microbiota and Possible Implication in Development of Diabetes Mellitus. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2022; 70:5945-5960. [PMID: 35549332 DOI: 10.1021/acs.jafc.1c07851] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/15/2023]
Abstract
Diabetes mellitus is characterized by having a disorder of glucose metabolism. The types of diabetes mellitus include type 1 diabetes mellitus, type 2 diabetes mellitus, gestational diabetes mellitus, and other specific types of diabetes mellitus. Many risk factors contribute to diabetes mellitus mainly including genetics, environment, obesity, and diet. In the recent years, gut microbiota has been shown to be linked to the development of diabetes. It has been reported that the gut microbiota composition of diabetic patients is different from that of healthy people. Although the mechanism behind the abnormality remains to be explored, most hypotheses focus on the inflammation response and leaky gut in relation to the changes in production of endotoxins and metabolites derived from the intestinal flora. Consequently, the above-mentioned abnormalities trigger a series of metabolic changes, gradually leading to development of hyperglycemia, insulin resistance, and diabetes. This review is (i) to summarize the differences in gut microbiota between diabetic patients and healthy people, (ii) to discuss the underlying mechanism(s) by which how lipopolysaccharide, diet, and metabolites of the gut microbiota affect diabetes, and (iii) to provide a new insight in the prevention and treatment of diabetes.
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Affiliation(s)
- Zinan Guo
- School of Food Science and Engineering, South China Food Safety Research Center, Foshan University, Foshan 528011, Guangdong, China
- School of Life Sciences, The Chinese University of Hong Kong, Shatin 999077, Hong Kong, China
| | - Jingjin Pan
- School of Food Science and Engineering, South China Food Safety Research Center, Foshan University, Foshan 528011, Guangdong, China
| | - Hanyue Zhu
- School of Food Science and Engineering, South China Food Safety Research Center, Foshan University, Foshan 528011, Guangdong, China
| | - Zhen-Yu Chen
- School of Life Sciences, The Chinese University of Hong Kong, Shatin 999077, Hong Kong, China
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17
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Metabolomics in Bariatric and Metabolic Surgery Research and the Potential of Deep Learning in Bridging the Gap. Metabolites 2022; 12:metabo12050458. [PMID: 35629961 PMCID: PMC9143741 DOI: 10.3390/metabo12050458] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2022] [Revised: 05/15/2022] [Accepted: 05/16/2022] [Indexed: 02/01/2023] Open
Abstract
During the past several years, there has been a shift in terminology from bariatric surgery alone to bariatric and metabolic surgery (BMS). More than a change in name, this signifies a paradigm shift that incorporates the metabolic effects of operations performed for weight loss and the amelioration of related medical problems. Metabolomics is a relatively novel concept in the field of bariatrics, with some consistent changes in metabolite concentrations before and after weight loss. However, the abundance of metabolites is not easy to handle. This is where artificial intelligence, and more specifically deep learning, would aid in revealing hidden relationships and would help the clinician in the decision-making process of patient selection in an individualized way.
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18
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Roux-En-Y Gastric Bypass (RYGB) Surgery during High Liquid Sucrose Diet Leads to Gut Microbiota-Related Systematic Alterations. Int J Mol Sci 2022; 23:ijms23031126. [PMID: 35163046 PMCID: PMC8835548 DOI: 10.3390/ijms23031126] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2021] [Revised: 01/13/2022] [Accepted: 01/17/2022] [Indexed: 12/17/2022] Open
Abstract
Roux-en-Y gastric bypass (RYGB) surgery has been proven successful in weight loss and improvement of co-morbidities associated with obesity. Chronic complications such as malabsorption of micronutrients in up to 50% of patients underline the need for additional therapeutic approaches. We investigated systemic RYGB surgery effects in a liquid sucrose diet-induced rat obesity model. After consuming a diet supplemented with high liquid sucrose for eight weeks, rats underwent RYGB or control sham surgery. RYGB, sham pair-fed, and sham ad libitum-fed groups further continued on the diet after recovery. Notable alterations were revealed in microbiota composition, inflammatory markers, feces, liver, and plasma metabolites, as well as in brain neuronal activity post-surgery. Higher fecal 4-aminobutyrate (GABA) correlated with higher Bacteroidota and Enterococcus abundances in RYGB animals, pointing towards the altered enteric nervous system (ENS) and gut signaling. Favorable C-reactive protein (CRP), serine, glycine, and 3-hydroxybutyrate plasma profiles in RYGB rats were suggestive of reverted obesity risk. The impact of liquid sucrose diet and caloric restriction mainly manifested in fatty acid changes in the liver. Our multi-modal approach reveals complex systemic changes after RYGB surgery and points towards potential therapeutic targets in the gut-brain system to mimic the surgery mode of action.
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19
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Wang L, Wang Z, Yu Y, Ren Z, Jia Y, Wang J, Li S, Jiang T. Metabolomics analysis of stool in rats with type 2 diabetes mellitus after single-anastomosis duodenal-ileal bypass with sleeve gastrectomy. Front Endocrinol (Lausanne) 2022; 13:1013959. [PMID: 36204098 PMCID: PMC9530139 DOI: 10.3389/fendo.2022.1013959] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 08/29/2022] [Indexed: 11/13/2022] Open
Abstract
BACKGROUND Single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) is one of the most effective bariatric procedures in the treatment of type 2 diabetes mellitus (T2DM). However, the mechanisms by which SADI-S improves T2DM are not well-known. OBJECTIVE To explore the effects of SADI-S on metabolites in the stool of rats with T2DM. METHODS Twenty rats were fed on high-fat diet and administered with a low-dose (30mg/kg) of streptozotocin to establish T2DM models. The rats were then randomly assigned to the SADI-S group (n=10) and sham operation group (n=9). Stool samples were collected from all rats at 8 weeks after surgery and stored at -80 °C. Metabolomics analysis was performed to identify differential metabolites through ultra- performance liquid chromatography-mass spectrometry. RESULTS At 8-week after surgery, rats of the SADI-S group showed significantly decreased fasting blood glucose, glucose tolerance test 2-hour, glycated haemoglobin, and body weight compared with those of the sham group. A total of 245 differential metabolites were identified between the two groups. Among them, 16 metabolites such as branched-chain amino acids (valine), aromatic amino acid (phenylalanine), bile acid (cholic acid, lithocholic acid, and β-muricholic acid), short-chain fatty acid (isobutyric acid), and phospholipid [lysoPE(17:0), lysoPE(20:3) and lysoPS(16:0)] were associated to the T2DM remission after SADI-S. CONCLUSION SADI-S improves T2DM in rats by regulating phenylalanine biosynthesis, valine, phenylalanine, alanine, glutamate, proline, bile acid, and phospholipid metabolism pathways.
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20
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Metabolomics in Bariatric Surgery: Towards Identification of Mechanisms and Biomarkers of Metabolic Outcomes. Obes Surg 2021; 31:4564-4574. [PMID: 34318371 DOI: 10.1007/s11695-021-05566-9] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2021] [Revised: 06/17/2021] [Accepted: 06/24/2021] [Indexed: 12/27/2022]
Abstract
Bariatric surgery has been widely performed for the treatment of obesity and type 2 diabetes. Efforts have been made to investigate the mechanisms underlying the metabolic effects achieved by bariatric surgery and to identify candidates who will benefit from this surgery. Metabolomics, which includes comprehensive profiling of metabolites in biological samples, has been utilized for various disease entities to discover pathophysiological metabolic pathways and biomarkers predicting disease progression or prognosis. Over the last decade, metabolomic studies on patients undergoing bariatric surgery have identified significant biomarkers related to metabolic effects. This review describes the significance, progress, and challenges for the future of metabolomics in the area of bariatric surgery.
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21
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Tu Y, Bao Y, Zhang P. Metabolic surgery in China: present and future. J Mol Cell Biol 2021; 13:mjab039. [PMID: 34240190 PMCID: PMC8697345 DOI: 10.1093/jmcb/mjab039] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Revised: 05/27/2021] [Accepted: 06/14/2021] [Indexed: 11/24/2022] Open
Abstract
Obesity and its related complications comprise a serious public health problem worldwide, and obesity is increasing in China. Metabolic surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic complications. The pathogenesis of obesity is complex and not yet fully understood. Here, we review the current efficacy and safety of metabolic surgery, as well as recent progress in mechanistic studies and surgical procedures in China. The exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.
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Affiliation(s)
- Yinfang Tu
- Department of Endocrinology and Metabolism, Shanghai
Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes
Institute, Shanghai Clinical Center of Diabetes, Shanghai Key Laboratory of
Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic
Disease, Shanghai 200233, China
| | - Yuqian Bao
- Department of Endocrinology and Metabolism, Shanghai
Jiao Tong University Affiliated Sixth People’s HospitalShanghai Diabetes
Institute, Shanghai Clinical Center of Diabetes, Shanghai Key Laboratory of
Diabetes Mellitus, Shanghai Key Clinical Center for Metabolic
Disease, Shanghai 200233, China
- Department of Endocrinology and Metabolism, Jinshan
District Central Hospital of Shanghai Sixth People's
Hospital, Shanghai 201599, China
| | - Pin Zhang
- Department of Bariatric and Metabolic Surgery,
Shanghai Jiao Tong University Affiliated Sixth People’s
Hospital, Shanghai 200233, China
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22
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Jääskeläinen T, Kärkkäinen O, Jokkala J, Klåvus A, Heinonen S, Auriola S, Lehtonen M, Hanhineva K, Laivuori H. A non-targeted LC-MS metabolic profiling of pregnancy: longitudinal evidence from healthy and pre-eclamptic pregnancies. Metabolomics 2021; 17:20. [PMID: 33515103 PMCID: PMC7846510 DOI: 10.1007/s11306-020-01752-5] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/26/2020] [Accepted: 11/25/2020] [Indexed: 12/25/2022]
Abstract
INTRODUCTION Maternal metabolism changes substantially during pregnancy. However, few studies have used metabolomics technologies to characterize changes across gestation. OBJECTIVES AND METHODS We applied liquid chromatography-mass spectrometry (LC-MS) based non-targeted metabolomics to determine whether the metabolic profile of serum differs throughout the pregnancy between pre-eclamptic and healthy women in the FINNPEC (Finnish Genetics of Preeclampsia Consortium) Study. Serum samples were available from early and late pregnancy. RESULTS Progression of pregnancy had large-scale effects to the serum metabolite profile. Altogether 50 identified metabolites increased and 49 metabolites decreased when samples of early pregnancy were compared to samples of late pregnancy. The metabolic signatures of pregnancy were largely shared in pre-eclamptic and healthy women, only urea, monoacylglyceride 18:1 and glycerophosphocholine were identified to be increased in the pre-eclamptic women when compared to healthy controls. CONCLUSIONS Our study highlights the need of large-scale longitudinal metabolomic studies in non-complicated pregnancies before more detailed understanding of metabolism in adverse outcomes could be provided. Our findings are one of the first steps for a broader metabolic understanding of the physiological changes caused by pregnancy per se.
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Affiliation(s)
- Tiina Jääskeläinen
- Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland.
- Department of Food and Nutrition, University of Helsinki, Helsinki, Finland.
| | - Olli Kärkkäinen
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Jenna Jokkala
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Anton Klåvus
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Seppo Heinonen
- Obstetrics and Gynecology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
| | - Seppo Auriola
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Marko Lehtonen
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland
| | - Kati Hanhineva
- Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
- Department of Biochemistry, Food Chemistry and Food Development Unit, University of Turku, Turku, Finland
| | - Hannele Laivuori
- Medical and Clinical Genetics, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- Institute for Molecular Medicine Finland (FIMM), Helsinki Institute of Life Science, University of Helsinki, Helsinki, Finland
- Department of Obstetrics and Gynecology, Faculty of Medicine and Health Technology, Tampere University Hospital and University of Tampere, Tampere, Finland
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23
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Eriksen F, Carlsson ER, Munk JK, Madsbad S, Fenger M. Fractionated free fatty acids and their relation to diabetes status after Roux-en-Y gastric bypass: A cohort study. Physiol Rep 2021; 9:e14708. [PMID: 33463892 PMCID: PMC7814490 DOI: 10.14814/phy2.14708] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2020] [Revised: 12/11/2020] [Accepted: 12/12/2020] [Indexed: 01/15/2023] Open
Abstract
Bariatric surgery is associated with near-immediate remission of type 2 diabetes and recently suggested as a treatment for type 2 diabetes. Specifically, Roux-en-Y gastric bypass has been a focus of much research, but still, the mechanisms of action are only partly elucidated. We aim to investigate whether some mechanisms might be mediated by free fatty acids (FFAs). We measured eight fractionated FFAs before and up to 2 years after Roux-en-Y gastric bypass surgery in 207 patients, divided into three groups. One non-diabetic group, one diabetic group with post-operative remission and one diabetic group with persistent diabetes after surgery. Pre- and postoperative levels of fractionated FFAs were compared within and between groups. The sum of the measured FFAs were lower in the group with persistent diabetes, compared to the other groups. The pre-surgery level of linoleic acid in the group with persistent diabetes was significantly lower compared to the other two groups. The levels of fractionated FFAs decreased from pre-surgery to three months after surgery, except for oleic acid and arachidonic acid and for Docosahexaenoic acid (DHA) in the non-diabetic group. The FFAs with decreasing levels from pre-surgery to three months post-surgery are all precursors to oleic acid, arachidonic acid, and DHA, respectively, which may imply a drift, indicating that they need to be sustained at an acceptable level for optimal metabolic function. The fact that the sum of the measured FFAs is lower in the group with persistent diabetes may suggest that this group and the group with diabetes remission represent two distinct types of type 2 diabetes. It is proposed that linoleic acid could be used as a biomarker to determine the plausibility for type 2 diabetes remission after Roux-en-Y gastric bypass surgery.
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Affiliation(s)
- Freja Eriksen
- Department of Clinical BiochemistryCopenhagen University Hospital HvidovreHvidovreDenmark
| | - Elin R. Carlsson
- Department of Clinical BiochemistryCopenhagen University Hospital HvidovreHvidovreDenmark
- Department of Clinical BiochemistryNordsjaellands HospitalUniversity of CopenhagenHillerodDenmark
| | - Jens K. Munk
- Department of Clinical BiochemistryCopenhagen University Hospital HvidovreHvidovreDenmark
| | - Sten Madsbad
- Department of EndocrinologyCopenhagen University Hospital HvidovreHvidovreDenmark
| | - Mogens Fenger
- Department of Clinical BiochemistryCopenhagen University Hospital HvidovreHvidovreDenmark
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Huang W, Zhong A, Xu H, Xu C, Wang A, Wang F, Li X, Liu Y, Zou J, Zhu H, Zheng X, Yi H, Guan J, Yin S. Metabolomics Analysis on Obesity-Related Obstructive Sleep Apnea After Weight Loss Management: A Preliminary Study. Front Endocrinol (Lausanne) 2021; 12:761547. [PMID: 35046891 PMCID: PMC8761762 DOI: 10.3389/fendo.2021.761547] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Accepted: 12/09/2021] [Indexed: 12/17/2022] Open
Abstract
OBJECTIVE Roux-en-Y gastric bypass (RYGB) surgery is an effective type of weight loss management and may improve obesity-related obstructive sleep apnea (OSA). Obese subjects who meet the criteria for surgery with OSA were enrolled. We investigated the metabolomic effects of RYGB on OSA. METHODS Clinical data, serum measurements including indices of glycolipid metabolism, and polysomnography (PSG) measurements were collected at baseline and 6 months after RYGB surgery. Metabolomic analysis was performed using ultra-performance liquid chromatography-mass spectrometry. RESULTS A group of 37 patients with obesity, type 2 diabetes (T2DM) and suspected OSA were enrolled of which 27 were OSA subjects. After RYGB surgery, metabolic outcomes and sleep parameters were all significantly improved. The OSA remission group had lower valine, isoleucine, and C24:1(cis-15) levels, and higher trimethylamine N-oxide, hippurate, and indole-3-propionic acid levels after RYGB surgery. A combination of preoperative indices (age, apnea-hypopnea index (AHI), fasting C-peptide level, and hippurate level) predicted the RYGB effect size in obese patients with T2DM and OSA, with an area under receiver operating characteristic curve of 0.947, specificity of 82.4%, and sensitivity of 100%. CONCLUSIONS RYGB surgery may significantly improve the metabolic status of patients with obesity, T2DM and OSA. A combination of preoperative indices (age, AHI, fasting C peptide level, and hippurate level) may be useful for predicting the effect size of RYGB in obese patients with T2DM and OSA. The mechanisms underlying OSA remission need to be explored.
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Affiliation(s)
- Weijun Huang
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Anyuan Zhong
- Department of Respiratory Diseases, The Second Affiliated Hospital of Soochow University, Suzhou, China
| | - Huajun Xu
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- *Correspondence: Hongliang Yi, ; Xiaojiao Zheng, ; Huajun Xu,
| | - Chong Xu
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Anzhao Wang
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Fan Wang
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Xinyi Li
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Yupu Liu
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Jianyin Zou
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Huaming Zhu
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Xiaojiao Zheng
- Center for Translational Medicine and Shanghai Key Laboratory of Diabetes Mellitus and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- *Correspondence: Hongliang Yi, ; Xiaojiao Zheng, ; Huajun Xu,
| | - Hongliang Yi
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
- *Correspondence: Hongliang Yi, ; Xiaojiao Zheng, ; Huajun Xu,
| | - Jian Guan
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
| | - Shankai Yin
- Department of Otorhinolaryngology Head and Neck Surgery and Otolaryngology Institute of Shanghai Jiao Tong University and Shanghai Key Laboratory of Sleep Disordered Breathing, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China
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Yoshida N, Kitahama S, Yamashita T, Hirono Y, Tabata T, Saito Y, Shinohara R, Nakashima H, Emoto T, Hirota Y, Takahashi T, Ogawa W, Hirata K. Metabolic alterations in plasma after laparoscopic sleeve gastrectomy. J Diabetes Investig 2021; 12:123-129. [PMID: 32563200 PMCID: PMC7779268 DOI: 10.1111/jdi.13328] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2020] [Revised: 05/30/2020] [Accepted: 06/14/2020] [Indexed: 02/06/2023] Open
Abstract
Laparoscopic sleeve gastrectomy (LSG) is an important therapeutic option for morbidly obese patients. Although LSG promotes sufficient weight loss, how LSG changes plasma metabolites remains unclear. We assessed changes in plasma metabolite levels after LSG. We collected plasma samples from 15 morbidly obese Japanese patients before and 3 months after LSG. A total of 48 metabolites were quantified using capillary electrophoresis time-of-flight mass spectrometry-based metabolomic profiling. Branched chain amino acids, several essential amino acids, choline, 2-hydroxybutyric acid, 2-oxoisovaleric acid and hypoxanthine were significantly decreased after LSG. Tricarboxylic acid cycle metabolites, including citric acid, succinic acid and malic acid, were significantly elevated after LSG. This is the first report to show dynamic alterations in plasma metabolite concentrations, as assessed using capillary electrophoresis time-of-flight mass spectrometry, in morbidly obese patients after LSG. Our results might show how LSG helps improve obesity, in part through metabolic status changes, and propose novel therapeutic targets to ameliorate obesity.
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Affiliation(s)
- Naofumi Yoshida
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Seiichi Kitahama
- Department of Bariatric and Metabolic SurgeryCenter for Obesity, Diabetes and EndocrinologyChibune General HospitalOsakaJapan
| | - Tomoya Yamashita
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Yasuko Hirono
- Department of Bariatric and Metabolic SurgeryCenter for Obesity, Diabetes and EndocrinologyChibune General HospitalOsakaJapan
| | - Tokiko Tabata
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Yoshihiro Saito
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | | | | | - Takuo Emoto
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Yushi Hirota
- Division of Diabetes and EndocrinologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Tetsuya Takahashi
- Division of Diabetes and EndocrinologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
- Department of Diabetes and EndocrinologyCenter for Obesity, Diabetes and EndocrinologyChibune General HospitalOsakaJapan
| | - Wataru Ogawa
- Division of Diabetes and EndocrinologyDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
| | - Ken‐ichi Hirata
- Division of Cardiovascular MedicineDepartment of Internal MedicineKobe University Graduate School of MedicineKobeJapan
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Herzog K, Berggren J, Al Majdoub M, Balderas Arroyo C, Lindqvist A, Hedenbro J, Groop L, Wierup N, Spégel P. Metabolic Effects of Gastric Bypass Surgery: Is It All About Calories? Diabetes 2020; 69:2027-2035. [PMID: 32527768 DOI: 10.2337/db20-0131] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/07/2020] [Accepted: 06/08/2020] [Indexed: 11/13/2022]
Abstract
Bariatric surgery is an efficient method to induce weight loss and also, frequently, remission of type 2 diabetes (T2D). Unpaired studies have shown bariatric surgery and dietary interventions to differentially affect multiple hormonal and metabolic parameters, suggesting that bariatric surgery causes T2D remission at least partially via unique mechanisms. In the current study, plasma metabolite profiling was conducted in patients with (n = 10) and without T2D (n = 9) subjected to Roux-en-Y gastric bypass surgery (RYGB). Mixed-meal tests were conducted at baseline, after the presurgical very-low-calorie diet (VLCD) intervention, immediately after RYGB, and after a 6-week recovery period. Thereby, we could compare fasted and postprandial metabolic consequences of RYGB and VLCD in the same patients. VLCD yielded a pronounced increase in fasting acylcarnitine levels, whereas RYGB, both immediately and after a recovery period, resulted in a smaller but opposite effect. Furthermore, we observed profound changes in lipid metabolism following VLCD but not in response to RYGB. Most changes previously associated with RYGB were found to be consequences of the presurgical dietary intervention. Overall, our results question previous findings of unique metabolic effects of RYGB and suggest that the effect of RYGB on the metabolite profile is mainly attributed to caloric restriction.
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Affiliation(s)
- Katharina Herzog
- Department of Chemistry, Centre for Analysis and Synthesis, Lund University, Lund, Sweden
| | - Johan Berggren
- Department of Surgery and Urology, Kalmar Hospital, Kalmar, Sweden
- Neuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University Diabetes Centre, Malmö, Sweden
| | - Mahmoud Al Majdoub
- Unit of Molecular Metabolism, Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden
| | | | - Andreas Lindqvist
- Neuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University Diabetes Centre, Malmö, Sweden
| | - Jan Hedenbro
- Neuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University Diabetes Centre, Malmö, Sweden
| | - Leif Groop
- Diabetes and Endocrinology, Department of Clinical Sciences, Lund University Diabetes Centre, Malmö, Sweden
| | - Nils Wierup
- Neuroendocrine Cell Biology, Department of Experimental Medical Science, Lund University Diabetes Centre, Malmö, Sweden
| | - Peter Spégel
- Department of Chemistry, Centre for Analysis and Synthesis, Lund University, Lund, Sweden
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27
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Yu D, Shu XO, Howard EF, Long J, English WJ, Flynn CR. Fecal metagenomics and metabolomics reveal gut microbial changes after bariatric surgery. Surg Obes Relat Dis 2020; 16:1772-1782. [PMID: 32747219 DOI: 10.1016/j.soard.2020.06.032] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/06/2020] [Accepted: 06/13/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Evidence from longitudinal patient studies regarding gut microbial changes after bariatric surgery is limited. OBJECTIVE To examine intraindividual changes in fecal microbiome and metabolites among patients undergoing Roux-en-Y gastric bypass or vertical sleeve gastrectomy. SETTING Observational study. METHODS Twenty patients were enrolled and provided stool samples before and 1 week, 1 month, and/or 3 months after surgery. Shallow shotgun metagenomics and untargeted fecal metabolomics were performed. Zero-inflated generalized additive models and linear mixed models were applied to identify fecal microbiome and metabolites changes, with adjustment for potential confounders and correction for multiple testing. RESULTS We enrolled 16 women and 4 men, including 16 white and 4 black participants (median age = 45 years; presurgery body mass index = 47.7 kg/m2). Ten patients had Roux-en-Y gastric bypass, 10 had vertical sleeve gastrectomy, and 14 patients provided postsurgery stool samples. Of 47 samples, median sequencing depth was 6.3 million reads and 1073 metabolites were identified. Microbiome alpha-diversity increased after surgery, especially at 3 months. Significant genus-level changes included increases in Odoribacter, Streptococcus, Anaerotruncus, Alistipes, Klebsiella, and Bifidobacterium, while decreases in Bacteroides, Coprocosccus, Dorea, and Faecalibacterium. Large increases in Streptococcus, Akkermansia, and Prevotella were observed at 3 months. Beta-diversity and fecal metabolites were also changed, including reduced caffeine metabolites, indoles, and butyrate. CONCLUSIONS Despite small sample size and missing repeated samples in some participants, our pilot study showed significant postsurgery changes in fecal microbiome and metabolites among bariatric surgery patients. Future large-scale, longitudinal studies are warranted to investigate gut microbial changes and their associations with metabolic outcomes after bariatric surgery.
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Affiliation(s)
- Danxia Yu
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee.
| | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Eric F Howard
- Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Jirong Long
- Division of Epidemiology, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Wayne J English
- Division of General Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
| | - Charles R Flynn
- Division of General Surgery, Department of Surgery, Vanderbilt University Medical Center, Nashville, Tennessee
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28
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Zhang CX, Wang XY, Lin ZZ, Wang HD, Qian YX, Li WW, Yang WZ, Guo DA. Highly selective monitoring of in-source fragmentation sapogenin product ions in positive mode enabling group-target ginsenosides profiling and simultaneous identification of seven Panax herbal medicines. J Chromatogr A 2020; 1618:460850. [DOI: 10.1016/j.chroma.2020.460850] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2019] [Revised: 12/28/2019] [Accepted: 01/02/2020] [Indexed: 01/17/2023]
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Yan K, Chen W, Zhu H, Lin G, Sun W, Liu X, Pan H, Wang L, Yang H, Liu M, Gong F. The Changes of Serum Metabolites in Diabetic GK Rats after Ileal Transposition Surgery. Obes Surg 2020; 29:882-890. [PMID: 30397878 DOI: 10.1007/s11695-018-3582-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Ileal transposition (IT) surgery could improve metabolism. Metabolomics has been applied comprehensively in analyzing the global dynamic alterations of metabolites. In the present study, we aimed to investigate serum metabolite alterations in diabetic Goto-Kakizaki (GK) rats after IT surgery. METHODS Male GK rats were subjected to IT and Sham-IT surgery. Six weeks later, body weight, food intake, fat mass, and serum biochemical parameters were measured. The serum metabolomic fingerprint was analyzed using ultra-performance liquid chromatography-mass spectrometry (LC-MS)-based, non-targeted metabolomic approach. The differential metabolites were identified using principal component analysis and orthogonal partial least squares discriminant analysis. Metabolic pathway analysis was performed using HMDB and KEGG databases. RESULTS The body weight, food intake, fat mass, serum levels of glucose and insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) of IT rats were significantly decreased when compared with Sham-IT rats (all P < 0.05). In the metabolomics analysis, ten serum differential metabolites were identified. Compared with Sham-IT rats, serum LysoPC(O-18:0) and PG(20:4/20:0) of IT rats were decreased, while genistein 4'-O-glucuronide, 5,6:8,9-Diepoxyergost-22-ene-3,7beta-diol, PI(16:0/18:2(9Z,12Z)), docosapentaenoic acid, 3-Oxo-4,6-choladienoic acid, 3-Oxocholic acid, and TG were increased. Pathway analysis highlighted the following pathways: ether lipid metabolism, alpha linolenic acid and linolenic acid metabolism, incretin synthesis and secretion, free fatty acid receptors, and biosynthesis of unsaturated fatty acids. CONCLUSIONS IT surgery could significantly decrease body weight and fat mass and improve glucose metabolism in diabetic GK rats. These beneficial effects might be related to the changes of serum metabolites which involved in lipid metabolism, bile acids, and incretin.
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Affiliation(s)
- Kemin Yan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Weijie Chen
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Huijuan Zhu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Guole Lin
- Department of Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Wei Sun
- Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/School of Basic Medicine, Peking Union Medical College, Beijing, 100730, China
| | - Xiaoyan Liu
- Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences/School of Basic Medicine, Peking Union Medical College, Beijing, 100730, China
| | - Hui Pan
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Linjie Wang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Hongbo Yang
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Meijuan Liu
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China
| | - Fengying Gong
- Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, 100730, China.
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Haange SB, Jehmlich N, Krügel U, Hintschich C, Wehrmann D, Hankir M, Seyfried F, Froment J, Hübschmann T, Müller S, Wissenbach DK, Kang K, Buettner C, Panagiotou G, Noll M, Rolle-Kampczyk U, Fenske W, von Bergen M. Gastric bypass surgery in a rat model alters the community structure and functional composition of the intestinal microbiota independently of weight loss. MICROBIOME 2020; 8:13. [PMID: 32033593 PMCID: PMC7007695 DOI: 10.1186/s40168-020-0788-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2019] [Accepted: 01/13/2020] [Indexed: 05/02/2023]
Abstract
BACKGROUND Roux-en-Y gastric bypass (RYGB) surgery is a last-resort treatment to induce substantial and sustained weight loss in cases of severe obesity. This anatomical rearrangement affects the intestinal microbiota, but so far, little information is available on how it interferes with microbial functionality and microbial-host interactions independently of weight loss. METHODS A rat model was employed where the RYGB-surgery cohort is compared to sham-operated controls which were kept at a matched body weight by food restriction. We investigated the microbial taxonomy and functional activity using 16S rRNA amplicon gene sequencing, metaproteomics, and metabolomics on samples collected from theileum, the cecum, and the colon, and separately analysed the lumen and mucus-associated microbiota. RESULTS Altered gut architecture in RYGB increased the relative occurrence of Actinobacteria, especially Bifidobacteriaceae and Proteobacteria, while in general, Firmicutes were decreased although Streptococcaceae and Clostridium perfringens were observed at relative higher abundances independent of weight loss. A decrease of conjugated and secondary bile acids was observed in the RYGB-gut lumen. The arginine biosynthesis pathway in the microbiota was altered, as indicated by the changes in the abundance of upstream metabolites and enzymes, resulting in lower levels of arginine and higher levels of aspartate in the colon after RYGB. CONCLUSION The anatomical rearrangement in RYGB affects microbiota composition and functionality as well as changes in amino acid and bile acid metabolism independently of weight loss. The shift in the taxonomic structure of the microbiota after RYGB may be mediated by the resulting change in the composition of the bile acid pool in the gut and by changes in the composition of nutrients in the gut. Video abstract.
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Affiliation(s)
- Sven-Bastiaan Haange
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
- Institute of Biochemistry, Faculty of Life Sciences, University of Leipzig, Leipzig, Germany
| | - Nico Jehmlich
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
| | - Ute Krügel
- Rudolf Boehm Institute of Pharmacology and Toxicology, Medical Faculty, University of Leipzig, Leipzig, Germany
| | - Constantin Hintschich
- Neuroendocrine Regulation of Energy Homeostasis Group, IFB Adiposity Diseases, Leipzig, Germany
| | - Dorothee Wehrmann
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
| | - Mohammed Hankir
- Neuroendocrine Regulation of Energy Homeostasis Group, IFB Adiposity Diseases, Leipzig, Germany
- Current address: Department of Experimental Surgery, Wuerzburg University Hospital, Wuerzburg, Germany
| | - Florian Seyfried
- Department of General, Visceral, Vascular and Pediatric Surgery, Wuerzburg University Hospital, Wuerzburg, Germany
| | - Jean Froment
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
| | - Thomas Hübschmann
- Department of Environmental Microbiology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
| | - Susann Müller
- Department of Environmental Microbiology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
| | - Dirk K. Wissenbach
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
- Current address: Institute of Forensic Medicine, Jena University Hospital, Jena, Germany
| | - Kang Kang
- Leibniz Institute for Natural Product Research and Infection Biology, Hans Knoll Institute, Jena, Germany
| | - Christian Buettner
- Institute for Bioanalysis, Faculty of Applied Sciences, Coburg University of Applied Sciences and Arts, Coburg, Germany
| | - Gianni Panagiotou
- Systems Biology and Bioinformatics Group, School of Biological Sciences, The University of Hong Kong, Hong Kong SAR, China
- Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China
| | - Matthias Noll
- Institute for Bioanalysis, Faculty of Applied Sciences, Coburg University of Applied Sciences and Arts, Coburg, Germany
| | - Ulrike Rolle-Kampczyk
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
| | - Wiebke Fenske
- Neuroendocrine Regulation of Energy Homeostasis Group, IFB Adiposity Diseases, Leipzig, Germany
| | - Martin von Bergen
- Department of Molecular Systems Biology, Helmholtz Centre for Environmental Research-UFZ, Leipzig, Germany
- Institute of Biochemistry, Faculty of Life Sciences, University of Leipzig, Leipzig, Germany
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Metabolomics analysis of Xanthoceras sorbifolia husks protection of rats against Alzheimer's disease using liquid chromatography mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2019; 1126-1127:121739. [DOI: 10.1016/j.jchromb.2019.121739] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/18/2019] [Revised: 07/25/2019] [Accepted: 07/29/2019] [Indexed: 11/29/2022]
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Shah RV, Hwang SJ, Yeri A, Tanriverdi K, Pico AR, Yao C, Murthy V, Ho J, Vitseva O, Demarco D, Shah S, Iafrati MD, Levy D, Freedman JE. Proteins Altered by Surgical Weight Loss Highlight Biomarkers of Insulin Resistance in the Community. Arterioscler Thromb Vasc Biol 2019; 39:107-115. [PMID: 30580566 PMCID: PMC6309981 DOI: 10.1161/atvbaha.118.311928] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Objective- Mechanisms of early and late improvements in cardiovascular risk after bariatric surgery and applicability to larger, at-risk populations remain unclear. We aimed to identify proteins altered after bariatric surgery and their relations to metabolic syndrome and diabetes mellitus. Approach and Results- We identified 19 proteins altered in 32 nonfasting plasma samples from a study of patients undergoing bariatric surgery who were evaluated preoperatively (visit 1) versus both early (visit 2; ≈3 months) and late (visit 3; ≈12 months) postoperative follow-up using predefined protein panels (Olink). Using in silico methods and publicly available gene expression repositories, we found that genes encoding 8 out of 19 proteins had highest expression in liver relative to other assayed tissues, with the top biological and disease processes, including major obesity-related vascular diseases. Of 19 candidate proteins in the surgical cohort, 6 were previously measured in >3000 FHS (Framingham Heart Study) participants (IGFBP [insulin-like growth factor binding protein]-1, IGFBP-2, P-selectin, CD163, LDL (low-density lipoprotein)-receptor, and PAI [plasminogen activator inhibitor]-1). A higher concentration of IGFBP-2 at baseline was associated with a lower risk of incident metabolic syndrome (odds ratio per log-normal unit, 0.45; 95% CI, 0.32-0.64; P=7.7×10-6) and diabetes mellitus (odds ratio, 0.63; 95% CI, 0.49-0.79; P=0.0001) after multivariable adjustment. Conclusions- Using a directed protein quantification platform (Olink), we identified known and novel proteins altered after surgical weight loss, including IGFBP-2. Future efforts in well-defined obesity intervention settings may further define and validate novel targets for the prevention of vascular disease in obesity.
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Affiliation(s)
- Ravi V. Shah
- Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Shih-Jen Hwang
- Framingham Heart Study of the National Heart, Lung, and Blood Institute, Framingham, MA, and the Population Sciences Branch of the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD
| | - Ashish Yeri
- Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | | | - Alexander R. Pico
- Gladstone Institutes, Data Science and Biotechnology, San Francisco, CA
| | - Chen Yao
- Framingham Heart Study of the National Heart, Lung, and Blood Institute, Framingham, MA, and the Population Sciences Branch of the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD
| | - Venkatesh Murthy
- Department of Medicine and Radiology, University of Michigan at Ann Arbor, Ann Arbor, MI
| | - Jennifer Ho
- Cardiology Division, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA
| | - Olga Vitseva
- University of Massachusetts at Worcester, Worcester, MA
| | | | - Sajani Shah
- Department of Surgery, Tufts University, Boston, MA
| | | | - Daniel Levy
- Framingham Heart Study of the National Heart, Lung, and Blood Institute, Framingham, MA, and the Population Sciences Branch of the National Heart, Lung, and Blood Institute of the National Institutes of Health, Bethesda, MD
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Wewer Albrechtsen NJ, Geyer PE, Doll S, Treit PV, Bojsen-Møller KN, Martinussen C, Jørgensen NB, Torekov SS, Meier F, Niu L, Santos A, Keilhauer EC, Holst JJ, Madsbad S, Mann M. Plasma Proteome Profiling Reveals Dynamics of Inflammatory and Lipid Homeostasis Markers after Roux-En-Y Gastric Bypass Surgery. Cell Syst 2018; 7:601-612.e3. [DOI: 10.1016/j.cels.2018.10.012] [Citation(s) in RCA: 68] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2018] [Revised: 09/10/2018] [Accepted: 10/25/2018] [Indexed: 12/16/2022]
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Fiamoncini J, Fernandes Barbosa C, Arnoni Junior JR, Araújo Junior JC, Taglieri C, Szego T, Gelhaus B, Possolo de Souza H, Daniel H, Martins de Lima T. Roux-en-Y Gastric Bypass Surgery Induces Distinct but Frequently Transient Effects on Acylcarnitine, Bile Acid and Phospholipid Levels. Metabolites 2018; 8:metabo8040083. [PMID: 30477108 PMCID: PMC6316856 DOI: 10.3390/metabo8040083] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 11/08/2018] [Accepted: 11/17/2018] [Indexed: 02/07/2023] Open
Abstract
Roux-en-Y gastric bypass (RYGB) is an effective method to achieve sustained weight loss, but the mechanisms responsible for RYGB effects have not yet been fully characterized. In this study, we profiled the concentrations of 143 lipid metabolites in dry blood spots (DBS) of RYGB patients. DBS from obese patients (BMI range 35⁻44 kg/m²) were collected 7 days before, 15 and 90 days after the surgery. LC-MS/MS was used to quantify acylcarnitines, phosphatidylcholines, sphingomyelins and bile acids. RYGB caused a rapid increase in acylcarnitine levels that proved to be only transient, contrasting with the sustained decrease in phosphatidylcholines and increase of sphingomyelins and bile acids. A PLS-DA analysis revealed a 3-component model (R² = 0.9, Q² = 0.74) with key metabolites responsible for the overall metabolite differences. These included the BCAA-derived acylcarnitines and sphingomyelins with 16 and 18 carbons. We found important correlations between the levels of BCAA-derived acylcarnitines and specific sphingomyelins with plasma cholesterol and triacylglycerol concentrations. Along with the marked weight loss and clinical improvements, RYGB induced specific alterations in plasma acylcarnitines, bile acid and phospholipid levels. This calls for more studies on RYGB effects aiming to elucidate the metabolic adaptations that follow this procedure.
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Affiliation(s)
- Jarlei Fiamoncini
- Department of Food Science and Experimental Nutrition, School of Pharmaceutical Sciences, University of São Paulo, 05508-060 São Paulo, Brazil.
- Nutrition and Food Sciences, Technische Universität München, 85354 Freising-Weihenstephan, Germany.
| | | | | | | | | | - Tiago Szego
- Instituto CIGO, 05508-060 São Paulo, Brazil.
| | - Barbara Gelhaus
- Nutrition and Food Sciences, Technische Universität München, 85354 Freising-Weihenstephan, Germany.
| | - Heraldo Possolo de Souza
- Laboratório de Emergências Clínicas (LIM 51), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, 05508-060 São Paulo, Brazil.
| | - Hannelore Daniel
- Nutrition and Food Sciences, Technische Universität München, 85354 Freising-Weihenstephan, Germany.
| | - Thais Martins de Lima
- Laboratório de Emergências Clínicas (LIM 51), Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, 05508-060 São Paulo, Brazil.
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Tomášová P, Bugáňová M, Pelantová H, Holubová M, Šedivá B, Železná B, Haluzík M, Maletínská L, Kuneš J, Kuzma M. Metabolomics Based on MS in Mice with Diet-Induced Obesity and Type 2 Diabetes Mellitus: the Effect of Vildagliptin, Metformin, and Their Combination. Appl Biochem Biotechnol 2018; 188:165-184. [DOI: 10.1007/s12010-018-2899-8] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2018] [Accepted: 09/26/2018] [Indexed: 12/26/2022]
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Brial F, Le Lay A, Dumas ME, Gauguier D. Implication of gut microbiota metabolites in cardiovascular and metabolic diseases. Cell Mol Life Sci 2018; 75:3977-3990. [PMID: 30101405 PMCID: PMC6182343 DOI: 10.1007/s00018-018-2901-1] [Citation(s) in RCA: 124] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2018] [Revised: 07/31/2018] [Accepted: 08/08/2018] [Indexed: 12/18/2022]
Abstract
Evidence from the literature keeps highlighting the impact of mutualistic bacterial communities of the gut microbiota on human health. The gut microbita is a complex ecosystem of symbiotic bacteria which contributes to mammalian host biology by processing, otherwise, indigestible nutrients, supplying essential metabolites, and contributing to modulate its immune system. Advances in sequencing technologies have enabled structural analysis of the human gut microbiota and allowed detection of changes in gut bacterial composition in several common diseases, including cardiometabolic disorders. Biological signals sent by the gut microbiota to the host, including microbial metabolites and pro-inflammatory molecules, mediate microbiome-host genome cross-talk. This rapidly expanding line of research can identify disease-causing and disease-predictive microbial metabolite biomarkers, which can be translated into novel biodiagnostic tests, dietary supplements, and nutritional interventions for personalized therapeutic developments in common diseases. Here, we review results from the most significant studies dealing with the association of products from the gut microbial metabolism with cardiometabolic disorders. We underline the importance of these postbiotic biomarkers in the diagnosis and treatment of human disorders.
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Affiliation(s)
- Francois Brial
- Sorbonne University, University Paris Descartes, INSERM UMR_S1138, Cordeliers Research Centre, 15 rue de l'Ecole de Médecine, 75006, Paris, France
| | - Aurélie Le Lay
- Sorbonne University, University Paris Descartes, INSERM UMR_S1138, Cordeliers Research Centre, 15 rue de l'Ecole de Médecine, 75006, Paris, France
| | - Marc-Emmanuel Dumas
- Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, London, UK
- McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, QC, H3A 0G1, Canada
| | - Dominique Gauguier
- Sorbonne University, University Paris Descartes, INSERM UMR_S1138, Cordeliers Research Centre, 15 rue de l'Ecole de Médecine, 75006, Paris, France.
- Section of Biomolecular Medicine, Division of Computational and Systems Medicine, Department of Surgery and Cancer, Faculty of Medicine, Imperial College London, Sir Alexander Fleming Building, London, UK.
- McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, QC, H3A 0G1, Canada.
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Wijayatunga NN, Sams VG, Dawson JA, Mancini ML, Mancini GJ, Moustaid‐Moussa N. Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity. Diabetes Metab Res Rev 2018; 34:e3045. [PMID: 30003682 PMCID: PMC6238211 DOI: 10.1002/dmrr.3045] [Citation(s) in RCA: 41] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2017] [Revised: 06/24/2018] [Accepted: 07/04/2018] [Indexed: 12/11/2022]
Abstract
AIM Bariatric surgery induces significant weight loss, increases insulin sensitivity, and reduces mortality, but the underlying mechanisms are not clear. It was hypothesized that Roux-en-Y gastric bypass (RYGB) surgery improves metabolic profile along with weight loss. The objective of this pilot study was to evaluate changes in serum metabolites and fatty acids (FA) at 2 weeks and 6 months after RYGB. MATERIALS AND METHODS Serum samples were collected pre-surgery, at 2 weeks and 6 months post-surgery from 20 patients undergoing RYGB surgery. Serum non-esterified free FA (NEFA) were measured. Serum metabolites and FA were measured using nuclear magnetic resonance spectroscopy and improved direct fatty acid methyl ester synthesis and the gas chromatography/mass spectrometry method, respectively, in subjects who completed follow-up at 6 months (n = 8). RESULTS Mean (standard deviation) percent total weight loss was 6.70% (1.7) and 24.91% (6.63) at 2 weeks (n = 15) and 6 months (n = 8) post-surgery, respectively. NEFA were significantly reduced at 6 months post-surgery (P = 0.001, n = 8). Serum branched chain amino acids, 2-aminobutyrate, butyrate, 2-hydroxybutyrate, 3-hydroxybutyrate, acetone, 2-methylglutarate, and 2-oxoisocaproate were significantly reduced, while serum alanine, glycine, pyruvate, and taurine were significantly elevated at 6 months post-surgery compared with pre-surgery (n = 8, P < 0.05). Also, serum FA C10:0, C13:0, C14:0, C15:0, and C18:0 increased significantly (n = 8, P < 0.05) by 6 months post-surgery. CONCLUSIONS Changes in serum metabolites and FA at 6 months post-RYGB surgery in this pilot study with limited number of participants are suggestive of metabolic improvement; larger studies are warranted for confirmation.
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Affiliation(s)
| | - Valerie G. Sams
- Department of SurgeryUniversity of Tennessee Medical Center KnoxvilleTNUSA
| | - John A. Dawson
- Department of Nutritional SciencesTexas Tech UniversityLubbockTXUSA
- Obesity Research ClusterTexas Tech UniversityLubbockTXUSA
- Center for Biotechnology and GenomicsTexas Tech UniversityLubbockTXUSA
| | - Matthew L. Mancini
- Department of SurgeryUniversity of Tennessee Medical Center KnoxvilleTNUSA
| | - Gregory J. Mancini
- Department of SurgeryUniversity of Tennessee Medical Center KnoxvilleTNUSA
| | - Naima Moustaid‐Moussa
- Department of Nutritional SciencesTexas Tech UniversityLubbockTXUSA
- Obesity Research ClusterTexas Tech UniversityLubbockTXUSA
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38
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Cameron SJ, Takáts Z. Mass spectrometry approaches to metabolic profiling of microbial communities within the human gastrointestinal tract. Methods 2018; 149:13-24. [DOI: 10.1016/j.ymeth.2018.04.027] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/01/2018] [Revised: 04/05/2018] [Accepted: 04/22/2018] [Indexed: 12/14/2022] Open
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Metabotypes of response to bariatric surgery independent of the magnitude of weight loss. PLoS One 2018; 13:e0198214. [PMID: 29856816 PMCID: PMC5983508 DOI: 10.1371/journal.pone.0198214] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/25/2017] [Accepted: 05/15/2018] [Indexed: 12/18/2022] Open
Abstract
Objective Bariatric surgery is considered the most efficient treatment for morbid obesity and its related diseases. However, its role as a metabolic modifier is not well understood. We aimed to determine biosignatures of response to bariatric surgery and elucidate short-term metabolic adaptations. Methods We used a LC- and FIA-ESI-MS/MS approach to quantify acylcarnitines, (lyso)phosphatidylcholines, sphingomyelins, amino acids, biogenic amines and hexoses in serum samples of subjects with morbid obesity (n = 39) before and 1, 3 and 6 months after bariatric surgery. K-means cluster analysis allowed to distinguish metabotypes of response to bariatric surgery. Results For the first time, global metabolic changes following bariatric surgery independent of the baseline health status of the subjects have been revealed. We identify two metabolic phenotypes (metabotypes) at the interval 6 months-baseline after surgery, which presented differences in the levels of compounds of urea metabolism, gluconeogenic precursors and (lyso)phospholipid particles. Clinically, metabotypes were different in terms of the degree of improvement in insulin resistance, cholesterol, low-density lipoproteins and uric acid independent of the magnitude of weight loss. Conclusions This study opens new perspectives and new hypotheses on the metabolic benefits of bariatric surgery and understanding of the biology of obesity and its associated diseases.
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40
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A high throughput metabolomics method and its application in female serum samples in a normal menstrual cycle based on liquid chromatography-mass spectrometry. Talanta 2018; 185:483-490. [PMID: 29759231 DOI: 10.1016/j.talanta.2018.03.087] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Revised: 03/20/2018] [Accepted: 03/25/2018] [Indexed: 12/21/2022]
Abstract
Periodical changes of steroid hormones have a great impact on the homeostasis of the female. However, there are few studies concerning the metabolome changes during the cycle. To study the periodic metabolic changes, a female cohort was enrolled with time-series serum samples collected during a menstrual cycle. To meet the requirement of the large-scale sample analysis, a high throughput metabolomics method was established by using an efficient sample preparation on a 96 well filter plate and a rapid LC condition in 12 min, which reduces about 70% of the samples preprocessing time and 60% analysis time. Evaluation of metabolite coverage and separation performances reflected that the method was robust for the large-scale metabolomics study. Using this method, we found that 12.6% of total detected ions including lipids, amino acids, citric acid, and so on were significantly changed during a menstrual cycle. Some metabolites were found periodically changed, which is similar to hormones (estrone and progesterone) during the cycle. These results show the novel high throughput method can be applied in large-scale metabolomics studies.
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41
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“Gear mechanism” of bariatric interventions revealed by untargeted metabolomics. J Pharm Biomed Anal 2018; 151:219-226. [DOI: 10.1016/j.jpba.2018.01.016] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2017] [Revised: 12/30/2017] [Accepted: 01/08/2018] [Indexed: 02/06/2023]
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42
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Samczuk P, Ciborowski M, Kretowski A. Application of Metabolomics to Study Effects of Bariatric Surgery. J Diabetes Res 2018; 2018:6270875. [PMID: 29713650 PMCID: PMC5866882 DOI: 10.1155/2018/6270875] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/12/2017] [Revised: 12/30/2017] [Accepted: 01/28/2018] [Indexed: 02/06/2023] Open
Abstract
Bariatric surgery was born in the 1950s at the University of Minnesota. From this time, it continues to evolve and, by the same token, gives new or better possibilities to treat not only obesity but also associated comorbidities. Metabolomics is also a relatively young science discipline, and similarly, it shows great potential for the comprehensive study of the dynamic alterations of the metabolome. It has been widely used in medicine, biology studies, biomarker discovery, and prognostic evaluations. Currently, several dozen metabolomics studies were performed to study the effects of bariatric surgery. LC-MS and NMR are the most frequently used techniques to study main effects of RYGB or SG. Research has yield many interesting results involving not only clinical parameters but also molecular modulations. Detected changes pertain to amino acid, lipids, carbohydrates, or gut microbiota alterations. It proves that including bariatric surgery to metabolic surgery is warranted. However, many molecular modulations after those procedures remain unexplained. Therefore, application of metabolomics to study this field seems to be a proper solution. New findings can suggest new directions of surgery technics modifications, contribute to broadening knowledge about obesity and diseases related to it, and perhaps develop nonsurgical methods of treatment in the future.
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Affiliation(s)
- Paulina Samczuk
- Clinical Research Centre, Medical University of Białystok, Białystok, Poland
| | - Michal Ciborowski
- Clinical Research Centre, Medical University of Białystok, Białystok, Poland
| | - Adam Kretowski
- Clinical Research Centre, Medical University of Białystok, Białystok, Poland
- Department of Endocrinology, Diabetology and Internal Medicine, Medical University of Białystok, Białystok, Poland
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43
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Sridharan GV, D'Alessandro M, Bale SS, Bhagat V, Gagnon H, Asara JM, Uygun K, Yarmush ML, Saeidi N. Multi-omic network-based interrogation of rat liver metabolism following gastric bypass surgery featuring SWATH proteomics. TECHNOLOGY 2017; 5:139-184. [PMID: 29780857 PMCID: PMC5956888 DOI: 10.1142/s233954781750008x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
Morbidly obese patients often elect for Roux-en-Y gastric bypass (RYGB), a form of bariatric surgery that triggers a remarkable 30% reduction in excess body weight and reversal of insulin resistance for those who are type II diabetic. A more complete understanding of the underlying molecular mechanisms that drive the complex metabolic reprogramming post-RYGB could lead to innovative non-invasive therapeutics that mimic the beneficial effects of the surgery, namely weight loss, achievement of glycemic control, or reversal of non-alcoholic steatohepatitis (NASH). To facilitate these discoveries, we hereby demonstrate the first multi-omic interrogation of a rodent RYGB model to reveal tissue-specific pathway modules implicated in the control of body weight regulation and energy homeostasis. In this study, we focus on and evaluate liver metabolism three months following RYGB in rats using both SWATH proteomics, a burgeoning label free approach using high resolution mass spectrometry to quantify protein levels in biological samples, as well as MRM metabolomics. The SWATH analysis enabled the quantification of 1378 proteins in liver tissue extracts, of which we report the significant down-regulation of Thrsp and Acot13 in RYGB as putative targets of lipid metabolism for weight loss. Furthermore, we develop a computational graph-based metabolic network module detection algorithm for the discovery of non-canonical pathways, or sub-networks, enriched with significantly elevated or depleted metabolites and proteins in RYGB-treated rat livers. The analysis revealed a network connection between the depleted protein Baat and the depleted metabolite taurine, corroborating the clinical observation that taurine-conjugated bile acid levels are perturbed post-RYGB.
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Affiliation(s)
- Gautham Vivek Sridharan
- Center for Engineering in Medicine, Harvard Medical School - Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA
| | - Matthew D'Alessandro
- Center for Engineering in Medicine, Harvard Medical School - Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA
| | - Shyam Sundhar Bale
- Center for Engineering in Medicine, Harvard Medical School - Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA
| | - Vicky Bhagat
- Warren Alpert Medical School of Brown University, 222 Richmond St., Providence, RI 02903, USA
| | - Hugo Gagnon
- Phenoswitch Bioscience, 3001 12e Avenue N, Sherbrooke, QC J1H 5N4, Canada
| | - John M Asara
- Beth Israel Deaconness Medical Center, 3 Blackfan Circle Rm 425, Boston, MA 02115, USA
| | - Korkut Uygun
- Center for Engineering in Medicine, Harvard Medical School - Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA
| | - Martin L Yarmush
- Center for Engineering in Medicine, Harvard Medical School - Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA
| | - Nima Saeidi
- Center for Engineering in Medicine, Harvard Medical School - Massachusetts General Hospital, 51 Blossom Street, Boston, MA 02114, USA
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de Mello VD, Lankinen MA, Lindström J, Puupponen-Pimiä R, Laaksonen DE, Pihlajamäki J, Lehtonen M, Uusitupa M, Tuomilehto J, Kolehmainen M, Törrönen R, Hanhineva K. Fasting serum hippuric acid is elevated after bilberry (Vaccinium myrtillus) consumption and associates with improvement of fasting glucose levels and insulin secretion in persons at high risk of developing type 2 diabetes. Mol Nutr Food Res 2017; 61. [PMID: 28556578 DOI: 10.1002/mnfr.201700019] [Citation(s) in RCA: 54] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2017] [Revised: 04/20/2017] [Accepted: 05/08/2017] [Indexed: 01/23/2023]
Abstract
SCOPE Urinary hippuric acid has been proposed as a biomarker for fruit, vegetable, and polyphenol consumption. We assessed how serum hippuric acid changes after a bilberry-enriched diet (BB; high anthocyanin intake) and another berry diet including strawberries, raspberries, and cloudberries (SRC; lower anthocyanin intake) and how these changes associate with insulin and glucose metabolism. METHODS AND RESULTS Hippuric acid was measured with LC-QTOF-MS metabolite profiling analysis from fasting serum samples at baseline and after an 8-week intervention in 47 individuals with features of the metabolic syndrome who were randomized to either a BB diet (n = 15), an SRC diet (n = 20) or a control diet (n = 12). Fasting serum hippuric acid increased significantly (3.5-fold, p = 0.001) only in the BB group and correlated with changes in fasting plasma glucose concentration (r = -0.54, p < 0.05) and insulin secretion (r = 0.59, p < 0.05). These associations were confirmed in the Finnish Diabetes Prevention Study (n = 198). CONCLUSION Fasting serum hippuric acid is increased after consumption of anthocyanin-rich bilberries, and may contribute to the beneficial effect of bilberry consumption through its associations with better glycemic control and β-cell function.
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Affiliation(s)
- Vanessa Df de Mello
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Maria A Lankinen
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Jaana Lindström
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland
| | | | - David E Laaksonen
- Institute of Clinical Medicine, Internal Medicine, Kuopio University Hospital, Finland
| | - Jussi Pihlajamäki
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Clinical Nutrition and Obesity Center, Kuopio University Hospital, Finland
| | - Marko Lehtonen
- School of Pharmacy, University of Eastern Finland, Kuopio, Finland.,LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland
| | - Matti Uusitupa
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,Research Unit, Kuopio University Hospital, Kuopio, Finland
| | - Jaakko Tuomilehto
- Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland.,Center for Vascular Prevention, Danube-University Krems, Austria.,Saudi Diabetes Research Group, King Abdulaziz University, Jeddah, Saudi Arabia
| | - Marjukka Kolehmainen
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Riitta Törrönen
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland
| | - Kati Hanhineva
- Institute of Public Health and Clinical Nutrition, Department of Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.,LC-MS Metabolomics Center, Biocenter Kuopio, Kuopio, Finland
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An in-source multiple collision-neutral loss filtering based nontargeted metabolomics approach for the comprehensive analysis of malonyl-ginsenosides from Panax ginseng , P. quinquefolius , and P. notoginseng. Anal Chim Acta 2017; 952:59-70. [DOI: 10.1016/j.aca.2016.11.032] [Citation(s) in RCA: 66] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/02/2016] [Revised: 11/10/2016] [Accepted: 11/13/2016] [Indexed: 11/22/2022]
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46
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Wang L, Ye H, Sun D, Meng T, Cao L, Wu M, Zhao M, Wang Y, Chen B, Xu X, Wang G, Hao H. Metabolic Pathway Extension Approach for Metabolomic Biomarker Identification. Anal Chem 2016; 89:1229-1237. [PMID: 27983783 DOI: 10.1021/acs.analchem.6b03757] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Discovery of metabolomic biomarkers represents an important task in disease diagnosis and therapy. Although the development of various analytical tools and online libraries facilitates the identification of biomarkers, the fast and reliable identification of new biomarkers that are not included in databases still represents a major bottleneck in the field of metabolomics. Here, we developed a metabolic pathway extension (MPE) approach to the fast characterization of metabolomic biomarkers. This approach was proposed based on a core concept that the whole metabolome is built from a limited number of initial metabolites via various kinds and multiple steps of metabolic reactions, and thus, theoretically, the whole metabolome might be mapped from the initial metabolites and metabolic reactions. Carnitine was used as an example of initial metabolites to validate this concept and the usefulness of MPE approach. The intragastric dosing of carnitine to mice induced a significant alternation of a total of 97 metabolites. Mass differences between each pair of metabolites were calculated and then matched with those of typical metabolic pathways automatically by an in-house developed program. Diagnostic ions and neutral losses were used for validating the matches. With this approach, 93 out of a total of 97 metabolites were putatively identified, while only half of them could be traced from the currently available online database. The MPE approach was further validated by applying to the identification of carnitine-associated biomarkers in a typical mice model of fasting, and extended to the development of bile acids submetabolome. Our study indicates that the MPE approach is highly useful for rapid and reliable identification of metabolically and structurally associated biomarkers.
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Affiliation(s)
- Lin Wang
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Hui Ye
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Di Sun
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Tuo Meng
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Lijuan Cao
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Mengqiu Wu
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Min Zhao
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Yun Wang
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Baoqiang Chen
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Xiaowei Xu
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Guangji Wang
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
| | - Haiping Hao
- Key Lab of Drug Metabolism and Pharmacokinetics, State Key Laboratory of Natural Medicines, China Pharmaceutical University , Tongjiaxiang #24, Nanjing 21009, China
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Zhao L, Ni Y, Yu H, Zhang P, Zhao A, Bao Y, Liu J, Chen T, Xie G, Panee J, Chen W, Rajani C, Wei R, Su M, Jia W, Jia W. Serum stearic acid/palmitic acid ratio as a potential predictor of diabetes remission after Roux-en-Y gastric bypass in obesity. FASEB J 2016; 31:1449-1460. [PMID: 28007782 DOI: 10.1096/fj.201600927r] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2016] [Accepted: 12/12/2016] [Indexed: 12/18/2022]
Abstract
Endogenous fatty acid metabolism that results in elongation and desaturation lipid products is thought to play a role in the development of type 2 diabetes mellitus (T2DM). In this study, we evaluated the potential of estimated elongase and desaturase activities for use as predictive markers for T2DM remission after Roux-en-Y gastric bypass (RYGB). The results of a targeted metabolomics approach from 2 independent studies were used to calculate 24 serum FA concentration ratios (product/precursor). Gene expression data from an open public data set was also analyzed. In a longitudinal study of 38 obese diabetic patients with RYGB, we found higher baseline stearic acid/palmitic acid (S/P) ratio. This ratio reflects an elovl6-encoded elongase enzyme activity that has been found to be associated with greater possibility for diabetes remission after RYGB [odds ratio, 2.16 (95% CI 1.10-4.26)], after adjustment for age, gender, body mass index, diabetes duration, glycosylated hemoglobin A1c, and fasting C-peptide. Our results were validated by examination of postsurgical elovl6 gene expression in morbidly obese patients. The association of S/P with the metabolic status of obese individuals was further validated in a cross-sectional cohort of 381 participants. In summary, higher baseline S/P was associated with greater probability of diabetes remission after RYGB and may serve as a diagnostic marker in preoperative patient assessment. - Zhao, L., Ni, Y., Yu, H., Zhang, P., Zhao, A., Bao, Y., Liu, J., Chen, T., Xie, G., Panee, J., Chen, W., Rajani, C., Wei, R., Su, M., Jia, W., Jia, W. Serum stearic acid/palmitic acid ratio as a potential predictor of diabetes remission after Roux-en-Y gastric bypass in obesity.
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Affiliation(s)
- Linjing Zhao
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,College of Chemistry and Chemical Engineering, Shanghai University of Engineering Science, Shanghai, China
| | - Yan Ni
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Haoyong Yu
- Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Pin Zhang
- Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; and
| | - Aihua Zhao
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Yuqian Bao
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China.,Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Jiajian Liu
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Tianlu Chen
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Guoxiang Xie
- University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Jun Panee
- Department of Cell and Molecular Biology, John A. Burns School of Medicine, University of Hawaii, Manoa, Hawaii, USA
| | - Wenlian Chen
- University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Cynthia Rajani
- University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Runmin Wei
- University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Mingming Su
- University of Hawaii Cancer Center, Honolulu, Hawaii, USA
| | - Weiping Jia
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; .,Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China
| | - Wei Jia
- Shanghai Key Laboratory of Diabetes Mellitus and Center for Translational Medicine, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, China; .,University of Hawaii Cancer Center, Honolulu, Hawaii, USA
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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.
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