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Loos CMM, Zhao S, Li L, Li J, Han W, Vanzant ES, McLeod KR. Essential oil supplementation improves insulin sensitivity and modulates the plasma metabolome of hyperinsulinemic horses. Front Vet Sci 2024; 11:1444581. [PMID: 39687851 PMCID: PMC11648227 DOI: 10.3389/fvets.2024.1444581] [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: 06/05/2024] [Accepted: 11/04/2024] [Indexed: 12/18/2024] Open
Abstract
The objective of this study was to investigate the effect of essential oil (EO) supplementation on insulin sensitivity (IS) and the plasma metabolome in insulin dysregulated (ID) horses. Horses were blocked by degree of IS and assigned randomly to treatment: oral daily bolus (50 mL) of either a plant derived EO supplement or carrier (CON). Mares were housed in dry lots with ad libitum access to grass hay and supplemented individually twice daily with a concentrate to meet nutrient requirements for mature horses. Before and after 6 wks of treatment, mares underwent a combined glucose-insulin tolerance test (CGIT) and an oral sugar test (OST) on separate days. Global metabolome analysis was conducted on plasma samples before and after treatment. Although treatment did not affect (p > 0.4) AUC or glucose clearance during CGIT, there was a treatment*covariate interaction (p ≤ 0.08) for insulin concentrations at 75 min (INS75) and positive phase time (PT) with EO decreasing both INS75 (p ≤ 0.002) and PT (p = 0.05) in horses with more severe initial degree of ID. Similarly, EO treatment reduced (p ≤ 0.006) insulinemic response to the OST in horses exhibiting higher pre-treatment responses (treatment*covariate, p = 0.004). There were 702 metabolites identified that were uniquely changed with EO treatment. Pathway analysis and biomarkers showed EO-mediated changes in amino acid, linoleic acid, mesaconic acid, TCA-cyle intermediates and bile acid metabolism. The directional changes in these pathways or biomarkers are consistent with changes in inulin sensitivity in other models. These data show that EO shifted the plasma metabolome and improved insulin sensitivity in horses.
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Affiliation(s)
- Caroline M. M. Loos
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, United States
| | - Shuang Zhao
- The Metabolomics Innovation Centre and Chemistry Department, University of Alberta, Edmonton, AB, Canada
| | - Liang Li
- The Metabolomics Innovation Centre and Chemistry Department, University of Alberta, Edmonton, AB, Canada
| | - Janet Li
- The Metabolomics Innovation Centre and Chemistry Department, University of Alberta, Edmonton, AB, Canada
| | - Wei Han
- The Metabolomics Innovation Centre and Chemistry Department, University of Alberta, Edmonton, AB, Canada
| | - Eric S. Vanzant
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, United States
| | - Kyle R. McLeod
- Department of Animal and Food Sciences, University of Kentucky, Lexington, KY, United States
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Benchoula K, Serpell CJ, Mediani A, Albogami A, Misnan NM, Ismail NH, Parhar IS, Ogawa S, Hwa WE. 1H NMR metabolomics insights into comparative diabesity in male and female zebrafish and the antidiabetic activity of DL-limonene. Sci Rep 2024; 14:3823. [PMID: 38360784 PMCID: PMC10869695 DOI: 10.1038/s41598-023-45608-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2023] [Accepted: 10/21/2023] [Indexed: 02/17/2024] Open
Abstract
Zebrafish have been utilized for many years as a model animal for pharmacological studies on diabetes and obesity. High-fat diet (HFD), streptozotocin and alloxan injection, and glucose immersion have all been used to induce diabetes and obesity in zebrafish. Currently, studies commonly used both male and female zebrafish, which may influence the outcomes since male and female zebrafish are biologically different. This study was designed to investigate the difference between the metabolites of male and female diabetic zebrafish, using limonene - a natural product which has shown several promising results in vitro and in vivo in treating diabetes and obesity-and provide new insights into how endogenous metabolites change following limonene treatment. Using HFD-fed male and female zebrafish, we were able to develop an animal model of T2D and identify several endogenous metabolites that might be used as diagnostic biomarkers for diabetes. The endogenous metabolites in males and females were different, even though both genders had high blood glucose levels and a high BMI. Treatment with limonene prevented high blood glucose levels and improved in diabesity zebrafish by limonene, through reversal of the metabolic changes caused by HFD in both genders. In addition, limonene was able to reverse the elevated expression of AKT during HFD.
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Affiliation(s)
- Khaled Benchoula
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia
| | | | - Ahmed Mediani
- Institute of Systems Biology (INBIOSIS), Universiti Kebangsaan Malaysia, 43600, UKM Bangi, Selangor, Malaysia
| | - Abdulaziz Albogami
- Biology Department, Faculty of Science, Al-Baha University, 65779-7738, Alaqiq, Saudi Arabia
| | - Norazlan Mohmad Misnan
- Institute for Medical Research Malaysia, No.1, Jalan Setia Murni U13/52, Seksyen U13, Setia Alam, 40170, Shah Alam, Selangor Darul Ehsan, Malaysia
| | - Nor Hadiani Ismail
- Atta-ur-Rahman Institute for Natural Products Discovery, UiTM Puncak Alam Campus, 42300, Puncak Alam, Selangor, Malaysia
| | - Ishwar S Parhar
- Monash University (Malaysia) BRIMS, Jeffrey Cheah School of Medicine and Health Sciences, Jalan Lagoon Selatan, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia
| | - Satoshi Ogawa
- Monash University (Malaysia) BRIMS, Jeffrey Cheah School of Medicine and Health Sciences, Jalan Lagoon Selatan, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia
| | - Wong Eng Hwa
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, 1, Jalan Taylors, 47500, Subang Jaya, Selangor, Malaysia.
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Wang M, Ou Y, Yuan XL, Zhu XF, Niu B, Kang Z, Zhang B, Ahmed A, Xing GQ, Su H. Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors. World J Diabetes 2024; 15:53-71. [PMID: 38313852 PMCID: PMC10835491 DOI: 10.4239/wjd.v15.i1.53] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2023] [Revised: 11/03/2023] [Accepted: 12/13/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND The lack of specific predictors for type-2 diabetes mellitus (T2DM) severely impacts early intervention/prevention efforts. Elevated branched-chain amino acids (BCAAs: Isoleucine, leucine, valine) and aromatic amino acids (AAAs: Tyrosine, tryptophan, phenylalanine)) show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies. However, improvement is needed to support its clinical utility. AIM To evaluate the effects of body mass index (BMI) and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight. METHODS Ninety-seven new-onset T2DM patients (< 12 mo) differing in BMI [normal weight (NW), n = 33, BMI = 22.23 ± 1.60; overweight, n = 42, BMI = 25.9 ± 1.07; obesity (OB), n = 22, BMI = 31.23 ± 2.31] from the First People's Hospital of Yunnan Province, Kunming, China, were studied. One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs. RESULTS Fasting serum AAAs, BCAAs, glutamate, and alanine were greater and high-density lipoprotein (HDL) was lower (P < 0.05, each) in OB-T2DM patients than in NW-T2DM patients, especially in male OB-T2DM patients. Arginine, histidine, leucine, methionine, and lysine were greater in male patients than in female patients. Moreover, histidine, alanine, glutamate, lysine, valine, methionine, leucine, isoleucine, tyrosine, phenylalanine, and tryptophan were significantly correlated with abdominal adiposity, body weight and BMI, whereas isoleucine, leucine and phenylalanine were negatively correlated with HDL. CONCLUSION Heterogeneously elevated amino acids, especially BCAAs/AAAs, across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development. The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals, whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals. This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.
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Affiliation(s)
- Min Wang
- School of Chemical Science and Technology, Yunnan University, Kunming 650091, Yunnan Province, China
| | - Yang Ou
- Department of Endocrinology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Xiang-Lian Yuan
- Department of Endocrinology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Xiu-Fang Zhu
- School of Chemical Science and Technology, Yunnan University, Kunming 650091, Yunnan Province, China
| | - Ben Niu
- Department of Endocrinology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Zhuang Kang
- Department of Endocrinology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
| | - Bing Zhang
- Clinical Laboratory, Nanchong Central Hospital & The Second Clinical Medical College of North Sichuan Medical University, Nanchong 637000, Sichuan Province, China
| | - Anwar Ahmed
- Department of Preventive Medicine and Biostatistics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, United States
| | - Guo-Qiang Xing
- The Affiliated Hospital and Second Clinical Medical College, North Sichuan Medical University, Nanchong 637000, Sichuan Province, China
- Department of Research and Development, Lotus Biotech.com LLC, Gaithersburg, MD 20878, United States
| | - Heng Su
- Department of Endocrinology, The First People’s Hospital of Yunnan Province, Kunming 650032, Yunnan Province, China
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Páez-Franco JC, Maravillas-Montero JL, Mejía-Domínguez NR, Torres-Ruiz J, Tamez-Torres KM, Pérez-Fragoso A, Germán-Acacio JM, Ponce-de-León A, Gómez-Martín D, Ulloa-Aguirre A. Metabolomics analysis identifies glutamic acid and cystine imbalances in COVID-19 patients without comorbid conditions. Implications on redox homeostasis and COVID-19 pathophysiology. PLoS One 2022; 17:e0274910. [PMID: 36126080 PMCID: PMC9488784 DOI: 10.1371/journal.pone.0274910] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Accepted: 09/06/2022] [Indexed: 11/18/2022] Open
Abstract
It is well known that the presence of comorbidities and age-related health issues may hide biochemical and metabolic features triggered by SARS-CoV-2 infection and other diseases associated to hypoxia, as they are by themselves chronic inflammatory conditions that may potentially disturb metabolic homeostasis and thereby negatively impact on COVID-19 progression. To unveil the metabolic abnormalities inherent to hypoxemia caused by COVID-19, we here applied gas chromatography coupled to mass spectrometry to analyze the main metabolic changes exhibited by a population of male patients less than 50 years of age with mild/moderate and severe COVID-19 without pre-existing comorbidities known to predispose to life-threatening complications from this infection. Several differences in serum levels of particular metabolites between normal controls and patients with COVID-19 as well as between mild/moderate and severe COVID-19 were identified. These included increased glutamic acid and reduced glutamine, cystine, threonic acid, and proline levels. In particular, using the entire metabolomic fingerprint obtained, we observed that glutamine/glutamate metabolism was associated with disease severity as patients in the severe COVID-19 group presented the lowest and higher serum levels of these amino acids, respectively. These data highlight the hypoxia-derived metabolic alterations provoked by SARS-CoV-2 infection in the absence of pre-existing co-morbidities as well as the value of amino acid metabolism in determining reactive oxygen species recycling pathways, which when impaired may lead to increased oxidation of proteins and cell damage. They also provide insights on new supportive therapies for COVID-19 and other disorders that involve altered redox homeostasis and lower oxygen levels that may lead to better outcomes of disease severity.
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Affiliation(s)
- José C. Páez-Franco
- Red de Apoyo a la Investigación (RAI), Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - José L. Maravillas-Montero
- Red de Apoyo a la Investigación (RAI), Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Nancy R. Mejía-Domínguez
- Red de Apoyo a la Investigación (RAI), Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Jiram Torres-Ruiz
- Emergency Medicine Department, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Karla M. Tamez-Torres
- Department of Infectology and Microbiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Alfredo Pérez-Fragoso
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Juan Manuel Germán-Acacio
- Red de Apoyo a la Investigación (RAI), Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Alfredo Ponce-de-León
- Department of Infectology and Microbiology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Diana Gómez-Martín
- Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
| | - Alfredo Ulloa-Aguirre
- Red de Apoyo a la Investigación (RAI), Universidad Nacional Autónoma de México e Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán, Mexico City, Mexico
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Zhang Q, Liu X, Gao M, Li X, Wang Y, Chang Y, Zhang X, Huo Z, Zhang L, Shan J, Zhang F, Zhu B, Yao W. The study of human serum metabolome on the health effects of glyphosate and early warning of potential damage. CHEMOSPHERE 2022; 298:134308. [PMID: 35302001 DOI: 10.1016/j.chemosphere.2022.134308] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Revised: 02/22/2022] [Accepted: 03/11/2022] [Indexed: 06/14/2023]
Abstract
Glyphosate is one of the most widely used herbicide with high efficiency, low toxicity and broad-spectrum. In recent decades, increasing evidence suggests that glyphosate may cause adverse health effects on human beings. However, until now, there is little data on the human metabolic changes. Since occupational workers are under greater health risks than ordinary people, the understanding regarding the health effects of glyphosate on occupational workers is very important for the early warning of potential damage. In this study, serum metabolic alterations in workers from three chemical factories were analyzed by gas chromatography-mass spectrometry (GC-MS) to assess the potential health risks caused by glyphosate at the molecular level. It was found that the levels of 27 metabolites changed significantly in the exposed group compared to the controls. The altered metabolic pathways, including amino acid metabolism, energy metabolism (glycolysis and TCA cycle) and glutathione metabolism (oxidative stress), etc., indicated a series of changes occur in health profile of the human body after glyphosate exposure, and the suboptimal health status of human may further evolve into various diseases, such as Parkinson's disease, renal and liver dysfunction, hepatocellular carcinoma, and colorectal cancer. Subsequently, 4 biomarkers (i.e., benzoic acid, 2-ketoisocaproic acid, alpha-ketoglutarate, and monoolein) were identified as potential biomarkers related to glyphosate exposure based on the partial correlation analyses, linear regression analyses, and FDR correction. Receiver-operating curve (ROC) analyses manifested that these potential biomarkers and their combinational pattern had good performance and potential clinical value to assess the potential health risk associated with glyphosate exposure while retaining high accuracy. Our findings provided new insights on mechanisms of health effects probably induced by glyphosate, and may be valuable for the health risk assessment of glyphosate exposure.
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Affiliation(s)
- QiuLan Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Xin Liu
- Department of Occupational Disease, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, 210009, China
| | - MengTing Gao
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - Xin Li
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - YiFei Wang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - YueYue Chang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - XueMeng Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - ZongLi Huo
- Department of Occupational Disease, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, 210009, China
| | - Li Zhang
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China
| | - JinJun Shan
- Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatics, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
| | - Feng Zhang
- Department of Occupational Disease, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, 210009, China.
| | - BaoLi Zhu
- Department of Occupational Disease, Jiangsu Provincial Center for Disease Prevention and Control, Nanjing, 210009, China.
| | - WeiFeng Yao
- School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing, 210023, China; Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, Nanjing University of Chinese Medicine, Nanjing, 210023, China.
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Effects of Fibroblast Growth Factor 21 on Lactate Uptake and Usage in Mice with Diabetes-Associated Cognitive Decline. Mol Neurobiol 2022; 59:5656-5672. [PMID: 35761156 DOI: 10.1007/s12035-022-02926-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Accepted: 06/11/2022] [Indexed: 10/17/2022]
Abstract
Fibroblast growth factor 21 (FGF21) is an endocrine hormone that exerts beneficial effects on glucose and lipid metabolic homeostasis. However, the impact of FGF21 on type 1 diabetes-associated cognitive decline (DACD) and its mechanisms of action remain unclear. In this study, we aimed to evaluate the effects of FGF21 on lactate uptake and usage in a mouse model of streptozotocin-induced DACD. Six-week-old male C57BL/6 mice were divided into the control, diabetic, and FGF21 (which received 2 mg/kg recombinant human FGF21) groups. At the end of the treatment period, learning and memory performance, nuclear magnetic resonance-based metabonomics, and expressions of various hippocampal protein were analyzed to determine the efficacy of FGF21. The results showed that compared to the control mice, the diabetic mice had reduced long-term memory performance after the hyperglycemic insult; decreased hippocampal levels of lactate dehydrogenase-B (LDH-B) activity, bioenergy metabolites, and monocarboxylate transporter 2 (MCT2); and increased lactate levels. Impaired phosphoinositide 3-kinase (PI3K) signaling was also observed in the diabetic mice. However, FGF21 treatment improved LDH-B activity, β-nicotinamide adenine dinucleotide, and ATP levels, and increased MCT2 expression and PI3K signaling pathway, which in turn improved the learning and memory defects. These findings demonstrated that the effects of FGF21 on DACD were associated with its ability to improve LDH-B-mediated lactate usage and MCT2-dependent lactate uptake. Further, these beneficial effects of FGF21 in the hippocampus were mediated by the PI3K signaling pathways.
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Hosseinkhani S, Arjmand B, Dilmaghani-Marand A, Mohammadi Fateh S, Dehghanbanadaki H, Najjar N, Alavi-Moghadam S, Ghodssi-Ghassemabadi R, Nasli-Esfahani E, Farzadfar F, Larijani B, Razi F. Targeted metabolomics analysis of amino acids and acylcarnitines as risk markers for diabetes by LC-MS/MS technique. Sci Rep 2022; 12:8418. [PMID: 35589736 PMCID: PMC9119932 DOI: 10.1038/s41598-022-11970-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2021] [Accepted: 04/27/2022] [Indexed: 11/29/2022] Open
Abstract
Diabetes is a common chronic disease affecting millions of people worldwide. It underlies various complications and imposes many costs on individuals and society. Discovering early diagnostic biomarkers takes excellent insight into preventive plans and the best use of interventions. Therefore, in the present study, we aimed to evaluate the association between the level of amino acids and acylcarnitines and diabetes to develop diabetes predictive models. Using the targeted LC-MS/MS technique, we analyzed fasting plasma samples of 206 cases and 206 controls that were matched by age, sex, and BMI. The association between metabolites and diabetes was evaluated using univariate and multivariate regression analysis with adjustment for systolic and diastolic blood pressure and lipid profile. To deal with multiple comparisons, factor analysis was used. Participants' average age and BMI were 61.6 years, 28.9 kg/m2, and 55% were female. After adjustment, Factor 3 (tyrosine, valine, leucine, methionine, tryptophan, phenylalanine), 5 (C3DC, C5, C5OH, C5:1), 6 (C14OH, C16OH, C18OH, C18:1OH), 8 (C2, C4OH, C8:1), 10 (alanine, proline) and 11 (glutamic acid, C18:2OH) were positively associated with diabetes. Inline, factor 9 (C4DC, serine, glycine, threonine) and 12 (citrulline, ornithine) showed a reverse trend. Some amino acids and acylcarnitines were found as potential risk markers for diabetes incidents that reflected the disturbances in the several metabolic pathways among the diabetic population and could be targeted to prevent, diagnose, and treat diabetes.
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Affiliation(s)
- Shaghayegh Hosseinkhani
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran, Iran
| | - Arezou Dilmaghani-Marand
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sahar Mohammadi Fateh
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Hojat Dehghanbanadaki
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Niloufar Najjar
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Alavi-Moghadam
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Ensieh Nasli-Esfahani
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farshad Farzadfar
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farideh Razi
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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8
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Ban Q, Sun X, Jiang Y, Cheng J, Guo M. Effect of synbiotic yogurt fortified with monk fruit extract on hepatic lipid biomarkers and metabolism in rats with type 2 diabetes. J Dairy Sci 2022; 105:3758-3769. [PMID: 35248379 DOI: 10.3168/jds.2021-21204] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2021] [Accepted: 01/14/2022] [Indexed: 01/03/2024]
Abstract
Monk fruit extract (MFE) is widely used as a sweetener in foods. In this study, the effects of the consumption of MFE-sweetened synbiotic yogurt on the lipid biomarkers and metabolism in the livers of type 2 diabetic rats were evaluated. The results revealed that the MFE-sweetened symbiotic yogurt affected the phosphatidylcholines, phosphatidylethanolamines, phosphatidylglycerol, lysophosphatidic acids, lysophosphatidylcholines, lysophosphatidylethanolamines, lysophosphatidylglycerols, lysophosphatidylinositols, lysophosphatidylserines, and fatty acid-hydroxy fatty acids biomarkers in the livers of type 2 diabetic rats. In addition, the consumption of the MFE-sweetened synbiotic yogurt significantly altered 12 hepatic metabolites, which are involved in phenylalanine metabolism, sphingolipid metabolism, bile secretion, and glyoxylate and dicarboxylate metabolism in the liver. Furthermore, a multiomics (metabolomic and transcriptomic) association study revealed that there was a significant correlation between the MFE-sweetened synbiotic yogurt and the metabolites and genes involved in fatty acid biosynthesis, bile secretion, and glyoxylate and dicarboxylate metabolism. The findings of this study will provide new insights on exploring the function of sweeteners for improving type 2 diabetes mellitus liver lipid biomarkers.
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Affiliation(s)
- Qingfeng Ban
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China; Key Laboratory of Dairy Science of Ministry of Education, Northeast Agricultural University, Harbin 150030, China
| | - Xiaomeng Sun
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China
| | - Yunqing Jiang
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China
| | - Jianjun Cheng
- College of Food Science, Northeast Agricultural University, Harbin, 150030, China.
| | - Mingruo Guo
- Department of Nutrition and Food Sciences, College of Agriculture and Life Sciences, University of Vermont, Burlington 05405.
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Benchoula K, Vohra MS, Parhar IS, Hwa WE. Metabolomics based biomarker identification of anti-diabetes and anti-obesity properties of Malaysian herbs. Metabolomics 2022; 18:12. [PMID: 35092490 DOI: 10.1007/s11306-022-01870-2] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/12/2020] [Accepted: 01/13/2022] [Indexed: 11/30/2022]
Abstract
BACKGROUND Today, obesity affects over one-third of the global population and is hugely considered the Industrial Revolution's side effect. This multi-factorial disease is continuously spreading across developing countries, including the Middle East and Southeast Asia region, where Malaysia and Darussalam Brunei are the most affected. The sedentary lifestyle and availability of surplus foods have dramatically increased the number of individuals with type 2 diabetes in these countries. Thus, an adequate medical strategy must be developed urgently to address and remedy these diseases. Natural sources have been attracting attention, especially in Malaysia, where most land areas are under plant cover. Metabolomics, as a prophylactic technique, has been used extensively in Malaysia to investigate the potential use and benefits of herbs to combat obesity and diabetes. AIM OF REVIEW This review aims to explain the application of the metabolomics approach in the study of anti-diabetes and anti-obesity activity of Malaysian herbs to identify the stand-up point for future advancement in using these herbs as a primary source for drug exploration. KEY SCIENTIFIC CONCEPTS OF REVIEW This review provides an overview of using metabolomics technique in studying the anti-diabetes and anti-obesity activity of Malaysian herbs. Specific emphasis is given to the changed metabolites in both in vivo and in vitro treatment of Malaysia herbs that might be future drugs for treating diabetes and obesity.
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Affiliation(s)
- Khaled Benchoula
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia
| | - Muhammad Sufyan Vohra
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia
| | - Ishwar S Parhar
- Jeffrey Cheah School of Medicine & Health Sciences, Monash University (Malaysia), BRIMS, Jalan Lagoon Selatan, Bandar Sunway, 47500, Subang Jaya, Selangor, Malaysia
| | - Wong Eng Hwa
- School of Medicine, Faculty of Health and Medical Sciences, Taylor's University, Subang Jaya, Malaysia.
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10
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He Y, Zhang H, Yang Y, Yu X, Zhang X, Xing Q, Zhang G. Using Metabolomics in Diabetes Management with Traditional Chinese Medicine: A Review. THE AMERICAN JOURNAL OF CHINESE MEDICINE 2022; 49:1813-1837. [PMID: 34961417 DOI: 10.1142/s0192415x21500865] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
The incidence of diabetes worldwide continues to rise, placing a huge economic and medical burden on human society. More than 90% of diabetic cases are type 2 diabetes (T2D). At present, the pathogenesis of T2D is not yet fully understood. Metabolomics uses high-resolution analytical techniques (typically NMR and MS) to help identify biomarkers associated with the risk of T2D and reveal potential pathogenesis. Many metabolites such as branched-chain amino acids (BCAAs), aromatic amino acids, glycine, 2-hydroxybutyric acid (2-HB), lysophosphatidylcholine (LPC) (18:2), and trehalose have proven to be biomarkers of T2D. Insulin resistance (IR) induced by BCAA in T2D mice is related to the activation of mammalian target of rapamycin (mTOR) and phosphorylation of insulin receptor substrate-1 (IRS1). Incomplete LCFA [Formula: see text]-oxidation promote acylcarnitine byproduct accumulation and stimulates proinflammatory NF[Formula: see text]B-related pathways to inhibit insulin action. Traditional Chinese Medicine (TCM) presents unique advantages in the treatment of T2D. Multiple metabolites and metabolic pathways have been identified in the treatment of TCM, providing valuable biomarkers and novel targets for drug therapy and pharmacological mechanism. Therefore, this paper reviews the modern achievements of metabolomics in T2D research and the progress of TCM management in recent years, in order to provide valuable information for related research.
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Affiliation(s)
- Yanling He
- Graduate School of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050091, P. R. China
| | - Hefang Zhang
- Graduate School of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050091, P. R. China.,Department of Endocrinology, First Affiliated Hospital of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050011, P. R. China
| | - Yufei Yang
- Graduate School of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050091, P. R. China
| | - Xianghui Yu
- Department of Endocrinology, First Affiliated Hospital of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050011, P. R. China
| | - Xiao Zhang
- Graduate School of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050091, P. R. China
| | - Qiaolin Xing
- Graduate School of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050091, P. R. China
| | - Gengliang Zhang
- Graduate School of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050091, P. R. China.,Department of Endocrinology, First Affiliated Hospital of Hebei University of Traditional, Chinese Medicine, Shijiazhuang 050011, P. R. China
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11
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Dong M, Yi Q, Shen D, Yan J, Jiang H, Xie J, Zhao L, Gao H. A combined metabolomics and molecular biology approach to reveal hepatic injury and underlying mechanisms after chronic l-lactate exposure in mice. Comput Struct Biotechnol J 2022; 20:3935-3945. [PMID: 35950184 PMCID: PMC9352416 DOI: 10.1016/j.csbj.2022.07.034] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/14/2022] [Revised: 07/20/2022] [Accepted: 07/20/2022] [Indexed: 11/30/2022] Open
Affiliation(s)
- Minjian Dong
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Qingqing Yi
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Danjie Shen
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Jiapin Yan
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Haowei Jiang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Jiaojiao Xie
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Liangcai Zhao
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
- Corresponding authors at: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
| | - Hongchang Gao
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
- Oujiang Laboratory (Zhejiang Lab for Regenerative Medicine, Vision and Brain Health), Key Laboratory of Alzheimer's Disease of Zhejiang Province, Wenzhou Medical University, Wenzhou 325035, China
- Corresponding authors at: School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, China.
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12
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Lv H, Zhang F, Liang C, Liu X, Ma Y, Li J, Ye Y, Si S, Liu Y, Heng H, Geng H. Decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus. Front Endocrinol (Lausanne) 2022; 13:1031798. [PMID: 36329881 PMCID: PMC9623307 DOI: 10.3389/fendo.2022.1031798] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 09/29/2022] [Indexed: 11/13/2022] Open
Abstract
The discovery of a large number of small pulmonary nodules and early diagnosis of lung cancer in the diabetic patients prompt us to re-examine the relationship between diabetes and the occurrence and development of lung cancer. The aim of this study was to explore the underlying metabolites changes in diabetes with NSCLC or benign nodule patients, and further to investigate the association of serum IGF-1 level and differentially expressed metabolites (DEMs). An untargeted metabolomics method was used to detect the changes of metabolism in diabetic patients with NSCLC on the platform of HR-MS. Serum level of IGF-1 was measured by ELISA. The patients were divided to three groups, DM, DLB (nodule), and DLC (cancer). we have identified numerous DEMs, which include amino acid, choline, and fatty acid derivatives. Further analysis of the involved metabolic pathways suggested that linoleate metabolism, tryptophan metabolism, histidine metabolism, putative anti-Inflammatory metabolites formation from EPA, and arachidonic acid metabolism were considered to be the most significant metabolic pathways between groups. Networks analysis suggested that a series of metabolites were associated with serum IGF-1among the three groups, which can be divided into 6 categories. Nine metabolites have been identified as the main DEMs among the DLC, DLB, and DM groups. In conclusion, metabolomics is a powerful and promising tool for the cancer risk evaluation in diabetic patients. Our results suggest that decreased IGF-1 level is associated with restrained amino acid metabolism in NSCLC with diabetes mellitus.
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Affiliation(s)
- Hehe Lv
- Department of Endocrinology, Graduate School of Bengbu Medical College, Bengbu, China
| | - Fan Zhang
- Department of Endocrinology, Xuzhou Central Hospital, Affiliated Clinical Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Can Liang
- Department of Medical Examination Center, Xuzhou Central hospital, Xuzhou, China
| | - Xuekui Liu
- Department of Endocrinology, Xuzhou Central Hospital, Affiliated Clinical Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yamei Ma
- Department of Endocrinology, Graduate School of Bengbu Medical College, Bengbu, China
| | - Jiayi Li
- Department of Endocrinology, Graduate School of Bengbu Medical College, Bengbu, China
| | - Yan Ye
- Department of Endocrinology, Xuzhou Central Hospital, Affiliated Clinical Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Shanwen Si
- Department of Endocrinology, Xuzhou Central Hospital, Affiliated Clinical Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
| | - Yaran Liu
- Institute of Medical Artificial Intelligence, Binzhou Medical College, Yantai, China
- *Correspondence: Houfa Geng, ; Hao Heng, ; Yaran Liu,
| | - Hao Heng
- Department of Endocrinology, Xuzhou Central Hospital, Affiliated Clinical Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- *Correspondence: Houfa Geng, ; Hao Heng, ; Yaran Liu,
| | - Houfa Geng
- Department of Endocrinology, Graduate School of Bengbu Medical College, Bengbu, China
- Department of Endocrinology, Xuzhou Central Hospital, Affiliated Clinical Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, China
- *Correspondence: Houfa Geng, ; Hao Heng, ; Yaran Liu,
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Hosseinkhani S, Aazami H, Hashemi E, Dehghanbanadaki H, Adibi-Motlagh B, Razi F. The trend in application of omics in type 2 diabetes researches; A bibliometric study. Diabetes Metab Syndr 2021; 15:102250. [PMID: 34419857 DOI: 10.1016/j.dsx.2021.102250] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/07/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 12/22/2022]
Abstract
AIMS Due to the importance of omics approaches in diabetes diagnosis, we were assumed to study the scientific activities on omics and type 2 diabetes worldwide. METHOD Bibliometric approach was utilized to evaluate the documents on proteomics, lipidomics, and metabolomics in patients with type 2 diabetes in the Scopus database from the beginning to 2020. The articles were screened by two reviewers and the number of publications and citations on omics and type 2 diabetes, top-ranked journals, top-cited articles, country co-contributions, co-authorships, author keywords, and terms were analyzed. RESULTS The scientific publications in this field consisted of 551 original articles, of which the USA shares the most percent, followed by China and Germany. The frequent keywords showed that the following hotspots were of interest: "Metabolomics, proteomics, and lipidomics as biomarkers for diabetes", "Omics and diabetic nephropathy", "The application of omics in obesity, insulin resistance, and type 2 diabetes". CONCLUSION This study showed an increasing trend in applying omics in type 2 diabetes researches and determined the leading producers in this field. Besides, the research hotspots and the main subjects of documents were provided for future research and policy decision-making.
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Affiliation(s)
- Shaghayegh Hosseinkhani
- Department of Clinical Biochemistry, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Hossein Aazami
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; Scientometrics Department, FarIdea Company, Tehran, Iran
| | - Ehsan Hashemi
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran; National Research Center for Transgenic Mouse, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran
| | - Hojat Dehghanbanadaki
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Behzad Adibi-Motlagh
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Farideh Razi
- Diabetes Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran.
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Wang Q, Dai X, Xiang X, Xu Z, Su S, Wei D, Zheng T, Shang EX, Qian D, Duan JA. A natural product of acteoside ameliorate kidney injury in diabetes db/db mice and HK-2 cells via regulating NADPH/oxidase-TGF-β/Smad signaling pathway. Phytother Res 2021; 35:5227-5240. [PMID: 34236110 DOI: 10.1002/ptr.7196] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2020] [Revised: 04/10/2021] [Accepted: 04/26/2021] [Indexed: 11/06/2022]
Abstract
This study was designed to investigate the protective effects and mechanisms of acteoside on DKD in diabetes male db/db mice and high glucose-induced HK-2 cells. The diabetes db/db mice were divided randomly into model group, metformin group, irbesartan group, and acteoside group. We observed the natural product of acteoside exhibiting a significant effect in renal protection through analyzing of biochemical indicators and endogenous metabolites, histopathological observations, and western blotting. HK-2 cells subjected to high glucose were used in invitro experiments. The molecular mechanisms of them were investigated by RT-PCR and western blot. Acteoside prevents high glucose-induced HK-2 cells and diabetes db/db mice by inhibiting NADPH/oxidase-TGF-β/Smad signaling pathway. Acteoside regulated the disturbed metabolic pathway of lipid metabolism, glyoxylate and dicarboxylate metabolism, and arachidonic acid metabolism. We discovered the natural product of acteoside exhibiting a significant effect in renal protection. This study paved the way for further exploration of pathogenesis, early diagnosis, and development of a new therapeutic agent for DKD.
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Affiliation(s)
- Qinwen Wang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xinxin Dai
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Xiang Xiang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhuo Xu
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Shulan Su
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Dandan Wei
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Tianyao Zheng
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Er-Xin Shang
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Dawei Qian
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jin-Ao Duan
- Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, and National and Local Collaborative Engineering Center of Chinese Medicinal Resources Industrialization and Formulae Innovative Medicine, and Key Laboratory of Chinese Medicinal Resources Recycling Utilization, State Administration of Traditional Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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15
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Jiang X, Chen X, Wang T, Li Y, Pan A, Wu J. Perfluorinated polymer modified vertical silicon nanowires as ultra low noise laser desorption ionization substrate for salivary metabolites profiling. Talanta 2021; 225:122022. [DOI: 10.1016/j.talanta.2020.122022] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/30/2020] [Revised: 12/07/2020] [Accepted: 12/13/2020] [Indexed: 12/12/2022]
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16
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Chambers A, Bury JJ, Minett T, Richardson CD, Brayne C, Ince PG, Shaw PJ, Garwood CJ, Heath PR, Simpson JE, Matthews FE, Wharton SB. Advanced Glycation End Product Formation in Human Cerebral Cortex Increases With Alzheimer-Type Neuropathologic Changes but Is Not Independently Associated With Dementia in a Population-Derived Aging Brain Cohort. J Neuropathol Exp Neurol 2021; 79:950-958. [PMID: 32766675 DOI: 10.1093/jnen/nlaa064] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2020] [Revised: 05/12/2020] [Accepted: 06/09/2020] [Indexed: 12/11/2022] Open
Abstract
Diabetes mellitus is a risk factor for dementia, and nonenzymatic glycosylation of macromolecules results in formation of advanced glycation end-products (AGEs). We determined the variation in AGE formation in brains from the Cognitive Function and Ageing Study population-representative neuropathology cohort. AGEs were measured on temporal neocortex by enzyme-linked immunosorbent assay (ELISA) and cell-type specific expression on neurons, astrocytes and endothelium was detected by immunohistochemistry and assessed semiquantitatively. Fifteen percent of the cohort had self-reported diabetes, which was not significantly associated with dementia status at death or neuropathology measures. AGEs were expressed on neurons, astrocytes and endothelium and overall expression showed a positively skewed distribution in the population. AGE measures were not significantly associated with dementia. AGE measured by ELISA increased with Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neurofibrillary tangle score (p = 0.03) and Thal Aβ phase (p = 0.04), while AGE expression on neurons (and astrocytes), detected immunohistochemically, increased with increasing Braak tangle stage (p < 0.001), CERAD tangle score (p = 0.002), and neuritic plaques (p = 0.01). Measures of AGE did not show significant associations with cerebral amyloid angiopathy, microinfarcts or neuroinflammation. In conclusion, AGE expression increases with Alzheimer's neuropathology, particular later stages but is not independently associated with dementia. AGE formation is likely to be important for impaired brain cell function in aging and Alzheimer's.
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Affiliation(s)
- Annabelle Chambers
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Joanna J Bury
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Thais Minett
- Institute of Public Health, University of Cambridge, Cambridge, UK
| | - Connor D Richardson
- Population Health Sciences Institute, University of Newcastle, Newcastle, UK
| | - Carol Brayne
- Institute of Public Health, University of Cambridge, Cambridge, UK
| | - Paul G Ince
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Pamela J Shaw
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Claire J Garwood
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Paul R Heath
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Julie E Simpson
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
| | - Fiona E Matthews
- Population Health Sciences Institute, University of Newcastle, Newcastle, UK
| | - Stephen B Wharton
- Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield, UK
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Bury JJ, Chambers A, Heath PR, Ince PG, Shaw PJ, Matthews FE, Brayne C, Simpson JE, Wharton SB. Type 2 diabetes mellitus-associated transcriptome alterations in cortical neurones and associated neurovascular unit cells in the ageing brain. Acta Neuropathol Commun 2021; 9:5. [PMID: 33407907 PMCID: PMC7788898 DOI: 10.1186/s40478-020-01109-y] [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] [Subscribe] [Scholar Register] [Received: 11/13/2020] [Accepted: 12/15/2020] [Indexed: 12/15/2022] Open
Abstract
Type 2 diabetes mellitus (T2D), characterised by peripheral insulin resistance, is a risk factor for dementia. In addition to its contribution to small and large vessel disease, T2D may directly damage cells of the brain neurovascular unit. In this study, we investigated the transcriptomic changes in cortical neurones, and associated astrocytes and endothelial cells of the neurovascular unit, in the ageing brain. Neurone, astrocyte, and endothelial cell-enriched mRNA, obtained by immuno-laser capture microdissection of temporal cortex (Brodmann area 21/22) from 6 cases with self-reported T2D in the Cognitive Function and Ageing Study neuropathology cohort, and an equal number of age and sex-matched controls, was assessed by microarray analysis. Integrated Molecular Pathway Level Analysis was performed using the Kyoto Encyclopaedia of Genes and Genomes database on significantly differentially expressed genes, defined as P < 0.05 and fold-change ± 1.2. Hub genes identified from Weighted Gene Co-expression Network Analysis were validated in neurones using the NanoString nCounter platform. The expression and cellular localisation of proteins encoded by selected candidate genes were confirmed by immunohistochemistry. 912, 2202, and 1227 genes were significantly differentially expressed between cases with self-reported T2D and controls in neurones, astrocytes, and endothelial cells respectively. Changes in cortical neurones included alterations in insulin and other signalling pathways, cell cycle, cellular senescence, inflammatory mediators, and components of the mitochondrial respiratory electron transport chain. Impaired insulin signalling was shared by neurovascular unit cells with, additionally, apoptotic pathway changes in astrocytes and dysregulation of advanced glycation end-product signalling in endothelial cells. Transcriptomic analysis identified changes in key cellular pathways associated with T2D that may contribute to neuronal damage and dysfunction. These effects on brain cells potentially contribute to a diabetic dementia, and may provide novel approaches for therapeutic intervention.
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Affiliation(s)
- Joanna J Bury
- Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK
| | - Annabelle Chambers
- Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK
| | - Paul R Heath
- Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK
| | - Paul G Ince
- Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK
| | - Pamela J Shaw
- Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK
| | - Fiona E Matthews
- Population Health Sciences Institute, Newcastle University, Newcastle upon Tyne, UK
| | - Carol Brayne
- Institute of Public Health, University of Cambridge, Cambridge, UK
| | - Julie E Simpson
- Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK
| | - Stephen B Wharton
- Sheffield Institute for Translational Neuroscience, University of Sheffield, 385a Glossop Road, Sheffield, S10 2HQ, UK.
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Hasanpour M, Iranshahy M, Iranshahi M. The application of metabolomics in investigating anti-diabetic activity of medicinal plants. Biomed Pharmacother 2020; 128:110263. [DOI: 10.1016/j.biopha.2020.110263] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2020] [Revised: 05/08/2020] [Accepted: 05/10/2020] [Indexed: 12/21/2022] Open
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Aspirin Modifies Inflammatory Mediators and Metabolomic Profiles and Contributes to the Suppression of Obesity-Associated Breast Cancer Cell Growth. Int J Mol Sci 2020; 21:ijms21134652. [PMID: 32629916 PMCID: PMC7369784 DOI: 10.3390/ijms21134652] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/23/2020] [Revised: 06/24/2020] [Accepted: 06/29/2020] [Indexed: 02/06/2023] Open
Abstract
Breast cancer is the most common cancer among women. Adiposity generally accompanies immune cell infiltration and cytokine secretion, which is ideal for tumor development. Aspirin is a chemopreventive agent against several types of cancer. The aim of this study was to investigate whether aspirin inhibits the growth of 4T1 breast cancer cells by inhibiting the inflammatory response and regulating the metabolomic profile of 3T3-L1 adipocytes. 3T3-L1 adipocyte-conditioned medium (Ad-CM) was used to mimic the obese adipose tissue microenvironment in 4T1 cells. The results revealed that aspirin inhibited macrophage chemoattractant protein (MCP-1), interleukin (IL-6), IL-1β, and plasminogen activator inhibitor (PAI-1) production in 3T3-L1 adipocytes stimulated by tumor necrosis factor-alpha (TNF-α) and lipopolysaccharide (LPS). In the obesity-associated model, Ad-CM significantly promoted 4T1 cell growth and migration, which were attenuated after aspirin treatment. The results of metabolic analyses using Ad-CM showed that amino acid metabolites and oxidative stress were increased in mature 3T3-L1 adipocytes compared to those in fibroblasts. Aspirin treatment modified metabolites involved in suppressing lipogenesis, oxidative stress, and neoplastic formation. In the relative fatty acid quantitation analysis of Ad-CM, aspirin diminished fatty acid contents of C16:1, C18:1, C18:2, C20:4, and C24:1. This study is the first to show that aspirin modifies the metabolomics and fatty acid composition of 3T3-L1 adipocytes and inhibits obesity-associated inflammation that contributes to obesity-related breast cancer cell growth and migration.
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Wei T, Shu Q, Ning J, Wang S, Li C, Zhao L, Zheng H, Gao H. The Protective Effect of Basic Fibroblast Growth Factor on Diabetic Nephropathy Through Remodeling Metabolic Phenotype and Suppressing Oxidative Stress in Mice. Front Pharmacol 2020; 11:66. [PMID: 32153399 PMCID: PMC7046551 DOI: 10.3389/fphar.2020.00066] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 01/22/2020] [Indexed: 12/11/2022] Open
Abstract
Diabetic nephropathy is a common complication in diabetes, but still lack of effective therapeutic strategies. This study aimed to investigate the therapeutic effect of basic fibroblast growth factor (bFGF) in db/db mice with diabetic nephropathy and explore its possible metabolic mechanisms using a nuclear magnetic resonance-based metabolomic approach. We found that bFGF treatment significantly alleviate urinary albumin to creatinine ratio and renal fibrosis in db/db mice, suggesting a potential renal protective effect. Metabolomics results reveal that bFGF remodeled metabolic phenotypes of the kidney and urine in db/db mice, mainly involving energy metabolism, methylamine metabolism, osmoregulation, and oxidative stress. Furthermore, the results show that bFGF-induced reductions of oxidative stress and apoptosis in db/db mice might be mediated by NOX-ROS-Nrf2 signaling. Therefore, our study suggests that the protective effect of bFGF on diabetic nephropathy could be mediated by remodeling metabolic phenotype and suppressing oxidative stress.
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Affiliation(s)
- Tingting Wei
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China.,Laboratory Animal Centre, Wenzhou Medical University, Wenzhou, China
| | - Qi Shu
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Jie Ning
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Shuaijie Wang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Chen Li
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Liangcai Zhao
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Hong Zheng
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Hongchang Gao
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
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21
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Xia H, Chen J, Sekar K, Shi M, Xie T, Hui KM. Clinical and metabolomics analysis of hepatocellular carcinoma patients with diabetes mellitus. Metabolomics 2019; 15:156. [PMID: 31773292 DOI: 10.1007/s11306-019-1619-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/24/2019] [Accepted: 11/19/2019] [Indexed: 12/26/2022]
Abstract
INTRODUCTION Diabetes and cancer are among the most frequent causes of death worldwide. Recent epidemiological findings have indicated a link between diabetes and cancer in several organs, particularly the liver. A number of epidemiological studies have demonstrated that diabetes is an established independent risk factor for hepatocellular carcinoma (HCC). However, the metabolites connecting diabetes and HCC remains less well understood. OBJECTIVES The study aimed to identify clinical and metabolomics differences of HCC from patients with/without diabetes using comprehensive global metabolomics analysis. METHODS Metabolite profiling was conducted with the Metabolon platform for 120 human diabetes/non-diabetes HCC tumor/normal tissues. Standard statistical analyses were performed using the Partek Genomics Suite on log-transformed data. Principal component analysis (PCA) was conducted using all and dysregulated metabolites. RESULTS We identified a group of metabolites that are differentially expressed in the tumor tissues of diabetes HCC compared to non-diabetes HCC patients. Meanwhile, we also identified a group of metabolites that are differentially expressed in the matched normal liver tissues of diabetes HCC compared to non-diabetes HCC patients. Some metabolites are consistently dysregulated in the tumor or matched normal tissues of HCC with or without diabetes. However, some metabolites, including 2-hydroxystearate, were only overexpressed in the tumor tissues of HCC with diabetes and associated with the glucose level. CONCLUSION Metabolic profiling identifies distinct dysregulated metabolites in HCC patients with/without diabetes.
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Affiliation(s)
- Hongping Xia
- Department of Pathology, School of Basic Medical Sciences & Sir Run Run Hospital & State Key Laboratory of Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, China.
- Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore.
| | - Jianxiang Chen
- Holistic Integrative Pharmacy Institutes (HIPI), Hangzhou Normal University, Hangzhou, China
| | - Karthik Sekar
- Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore
| | - Ming Shi
- Department of Hepatobiliary Oncology, Cancer Center, Sun Yat-sen University, Guangzhou, China
| | - Tian Xie
- Holistic Integrative Pharmacy Institutes (HIPI), Hangzhou Normal University, Hangzhou, China
| | - Kam M Hui
- Department of Pathology, School of Basic Medical Sciences & Sir Run Run Hospital & State Key Laboratory of Reproductive Medicine & Key Laboratory of Antibody Technique of National Health Commission, Nanjing Medical University, Nanjing, China.
- Laboratory of Cancer Genomics, Division of Cellular and Molecular Research, National Cancer Centre, Singapore, Singapore.
- Holistic Integrative Pharmacy Institutes (HIPI), Hangzhou Normal University, Hangzhou, China.
- Institute of Molecular and Cell Biology, A*STAR, Biopolis Drive Proteos, Singapore, Singapore.
- Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
- Cancer and Stem Cell Biology Program, Duke-NUS Medical School, Singapore, Singapore.
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22
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Lei X, Zhang C. Predicting metabolite-disease associations based on KATZ model. BioData Min 2019; 12:19. [PMID: 31673292 PMCID: PMC6815005 DOI: 10.1186/s13040-019-0206-z] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/14/2019] [Accepted: 09/12/2019] [Indexed: 11/17/2022] Open
Abstract
BACKGROUND Increasing numbers of evidences have illuminated that metabolites can respond to pathological changes. However, identifying the diseases-related metabolites is a magnificent challenge in the field of biology and medicine. Traditional medical equipment not only has the limitation of its accuracy but also is expensive and time-consuming. Therefore, it's necessary to take advantage of computational methods for predicting potential associations between metabolites and diseases. RESULTS In this study, we develop a computational method based on KATZ algorithm to predict metabolite-disease associations (KATZMDA). Firstly, we extract data about metabolite-disease pairs from the latest version of HMDB database for the materials of prediction. Then we take advantage of disease semantic similarity and the improved disease Gaussian Interaction Profile (GIP) kernel similarity to obtain more reliable disease similarity and enhance the predictive performance of our proposed computational method. Simultaneously, KATZ algorithm is applied in the domains of metabolomics for the first time. CONCLUSIONS According to three kinds of cross validations and case studies of three common diseases, KATZMDA is worth serving as an impactful measuring tool for predicting the potential associations between metabolites and diseases.
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Affiliation(s)
- Xiujuan Lei
- School of Computer Science, Shaanxi Normal University, Xi’an, 710119 Shaanxi China
| | - Cheng Zhang
- School of Computer Science, Shaanxi Normal University, Xi’an, 710119 Shaanxi China
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Satheesh G, Ramachandran S, Jaleel A. Metabolomics-Based Prospective Studies and Prediction of Type 2 Diabetes Mellitus Risks. Metab Syndr Relat Disord 2019; 18:1-9. [PMID: 31634052 DOI: 10.1089/met.2019.0047] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2023] Open
Abstract
The preceding decade has witnessed an intense upsurge in the diabetic population across the world making type 2 diabetes mellitus (T2DM) more of an epidemic than a lifestyle disease. Metabolic disorders are often latent for a while before becoming clinically evident, thus reinforcing the pursuit of early biomarkers of metabolic alterations. A prospective study along with metabolic profiling is the most appropriate way to detect the early pathophysiological changes in metabolic diseases such as T2DM. The aim of this review was to summarize the different potential biomarkers of T2DM identified in prospective studies, which used tools of metabolomics. The review also demonstrates on how metabolomic profiling-based prospective studies can be used to address a concern like population-specific disease mechanism. We performed a literature search on metabolomics-based prospective studies on T2DM using the key words "metabolomics," "Type 2 diabetes," "diabetes mellitus", "metabolite profiling," "prospective study," "metabolism," and "biomarker." Additional articles that were obtained from the reference lists of the articles obtained using the above key words were also examined. Articles on dietary intake, type 1 diabetes mellitus, and gestational diabetes were excluded. The review revealed that many studies showed a direct association of branched-chain amino acids and an inverse association of glycine with T2DM. Majority of the prospective studies conducted were targeted metabolomics-based, with Caucasians as their study cohort. The whole disease risk in populations, including Asians, could therefore not be identified. This review proposes the utility of prospective studies in conjunction with metabolomics platform to unravel the altered metabolic pathways that contribute to the risk of T2DM.
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Affiliation(s)
- Gopika Satheesh
- Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India
| | | | - Abdul Jaleel
- Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, India
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24
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Jacyna J, Wawrzyniak R, Balayssac S, Gilard V, Malet-Martino M, Sawicka A, Kordalewska M, Nowicki Ł, Kurek E, Bulska E, Patejko M, Markuszewski M, Gutknecht P, Matuszewski M, Siebert J, Kaliszan R, Markuszewski MJ. Urinary metabolomic signature of muscle-invasive bladder cancer: A multiplatform approach. Talanta 2019; 202:572-579. [DOI: 10.1016/j.talanta.2019.05.039] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2018] [Revised: 05/07/2019] [Accepted: 05/08/2019] [Indexed: 12/25/2022]
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25
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Goodarzi P, Alavi-Moghadam S, Payab M, Larijani B, Rahim F, Gilany K, Bana N, Tayanloo-Beik A, Foroughi Heravani N, Hadavandkhani M, Arjmand B. Metabolomics Analysis of Mesenchymal Stem Cells. INTERNATIONAL JOURNAL OF MOLECULAR AND CELLULAR MEDICINE 2019; 8:30-40. [PMID: 32351907 PMCID: PMC7175611 DOI: 10.22088/ijmcm.bums.8.2.30] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/13/2019] [Accepted: 05/20/2019] [Indexed: 12/12/2022]
Abstract
Various mesenchymal stem cells as easily accessible and multipotent cells can share different essential signaling pathways related to their stemness ability. Understanding the mechanism of stemness ability can be useful for controlling the stem cells for regenerative medicine targets. In this context, OMICs studies can analyze the mechanism of different stem cell properties or stemness ability via a broad range of current high-throughput techniques. This field is fundamentally directed toward the analysis of whole genome (genomics), mRNAs (transcriptomics), proteins (proteomics) and metabolites (metabolomics) in biological samples. According to several studies, metabolomics is more effective than other OMICs ّfor various system biology concerns. Metabolomics can elucidate the biological mechanisms of various mesenchymal stem cell function by measuring their metabolites such as their secretome components. Analyzing the metabolic alteration of mesenchymal stem cells can be useful to promote their regenerative medicine application.
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Affiliation(s)
- Parisa Goodarzi
- Brain and Spinal Cord Injury Research Center, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Sepideh Alavi-Moghadam
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Moloud Payab
- Obesity and Eating Habits Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Bagher Larijani
- Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical sciences, Tehran, Iran
| | - Fakher Rahim
- Health Research Institute, Thalassemia and Hemoglobinopathies Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran
| | - Kambiz Gilany
- Integrative Oncology Department, Breast Cancer Research Center, Motamed Cancer Institute, ACECR, Tehran, Iran .,Department of Biomedical Sciences, University of Antwerp, Belgium
| | - Nikoo Bana
- Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Akram Tayanloo-Beik
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Najmeh Foroughi Heravani
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mahdieh Hadavandkhani
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Babak Arjmand
- Cell Therapy and Regenerative Medicine Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran .,Metabolomics and Genomics Research Center, Endocrinology and Metabolism Molecular- Cellular Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
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26
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Xiao D, Hu Y, Fu Y, Wang R, Zhang H, Li M, Li Z, Zhang Y, Xuan L, Li X, Xu C, Zhang Y, Yang B. Emodin improves glucose metabolism by targeting microRNA-20b in insulin-resistant skeletal muscle. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2019; 59:152758. [PMID: 31004884 DOI: 10.1016/j.phymed.2018.11.018] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/28/2018] [Revised: 10/27/2018] [Accepted: 11/15/2018] [Indexed: 06/09/2023]
Abstract
BACKGROUND Emerging evidence has indicated the therapeutic potential of emodin with its multiple pharmacological effects. PURPOSE To evaluate role of emodin in regulating insulin resistance (IR) and to elucidate the underlying molecular mechanisms. STUDY DESIGN/METHODS Fasting blood glucose (FBG) and lipid levels were measured before and after intragastric administration of emodin in type 2 diabetes mellitus (T2DM) rats. Glucose consumption was determined in L6 cells to investigate the effect of emodin on glucose metabolism. Expression of miR-20b and SMAD7 was quantified by real-time PCR for mRNAs or western blot analysis for proteins. RESULTS Emodin ameliorated hyperglycemia and dyslipidemia in T2DM rats, and glucose metabolism in a concentration- and time-dependent manner. MiR-20b was markedly upregulated in the setting of IR and overexpression of miR-20b disrupted glucose metabolism by repressing SMAD7 in L6 cells. Knockdown of this miRNA produced the opposite effects. Emodin abolished the abnormal upregulation of miR-20b and indirectly upregulated SMAD7. CONCLUSION Emodin improves glucose metabolism to produce anti-IR effects, and downregulation of miR-20b thereby upregulation of SMAD7 is an underlying mechanism for the beneficial effects of emodin.
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Affiliation(s)
- Dan Xiao
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Yingying Hu
- Department of Pharmacy, the First Affiliated Hospital of Harbin Medical University, Harbin 150081, China
| | - Yujie Fu
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Rui Wang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Haiying Zhang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Mingqi Li
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Zhange Li
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Ying Zhang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Lina Xuan
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Xin Li
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China
| | - Chaoqian Xu
- Mudanjiang Medical University, 157000, China
| | - Yong Zhang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China; Institute of Metabolic Disease, Heilongjiang Academy of Medical Science, Harbin, 150086, China.
| | - Baofeng Yang
- Department of Pharmacology (State-Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Research, Ministry of Education), Harbin Medical University, Harbin 150081, China; Department of Pharmacology and Therapeutics, Melbourne School of Biomedical Sciences, Faculty of Medicine, Dentistry and Health Sciences, the University of Melbourne, Melbourne, 3010, Australia.
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27
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Comparison of the microbiome, metabolome, and lipidome of obese and non-obese horses. PLoS One 2019; 14:e0215918. [PMID: 31013335 PMCID: PMC6478336 DOI: 10.1371/journal.pone.0215918] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2018] [Accepted: 04/10/2019] [Indexed: 12/12/2022] Open
Abstract
Metabolic diseases such as obesity and type 2 diabetes in humans have been linked to alterations in the gastrointestinal microbiota and metabolome. Knowledge of these associations has improved our understanding of the pathophysiology of these diseases and guided development of diagnostic biomarkers and therapeutic interventions. The cellular and molecular pathophysiology of equine metabolic syndrome (EMS) and obesity in horses, however, remain ill-defined. Thus, the objectives of this study were to characterize the fecal microbiome, fecal metabolome, and circulating lipidome in obese and non-obese horses. The fecal microbiota, fecal metabolome, and serum lipidome were evaluated in obese (case) horses (n = 20) and non-obese (control) horses (n = 20) matched by farm of origin (n = 7). Significant differences in metabolites of the mitochondrial tricarboxylic acid cycle and circulating free fatty acids were identified in the obese horses compared to the non-obese horses. These results indicate that the host and bacterial metabolism should be considered important in obese horses. Further studies to determine whether these associations are causal and the mechanistic basis of the association are warranted because they might reveal diagnostic biomarkers and therapeutic interventions to mitigate obesity, EMS, and sequelae including laminitis.
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28
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Mellon SH, Bersani FS, Lindqvist D, Hammamieh R, Donohue D, Dean K, Jett M, Yehuda R, Flory J, Reus VI, Bierer LM, Makotkine I, Abu Amara D, Henn Haase C, Coy M, Doyle FJ, Marmar C, Wolkowitz OM. Metabolomic analysis of male combat veterans with post traumatic stress disorder. PLoS One 2019; 14:e0213839. [PMID: 30883584 PMCID: PMC6422302 DOI: 10.1371/journal.pone.0213839] [Citation(s) in RCA: 54] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2018] [Accepted: 03/02/2019] [Indexed: 12/26/2022] Open
Abstract
Posttraumatic stress disorder (PTSD) is associated with impaired major domains of psychology and behavior. Individuals with PTSD also have increased co-morbidity with several serious medical conditions, including autoimmune diseases, cardiovascular disease, and diabetes, raising the possibility that systemic pathology associated with PTSD might be identified by metabolomic analysis of blood. We sought to identify metabolites that are altered in male combat veterans with PTSD. In this case-control study, we compared metabolomic profiles from age-matched male combat trauma-exposed veterans from the Iraq and Afghanistan conflicts with PTSD (n = 52) and without PTSD (n = 51) (‘Discovery group’). An additional group of 31 PTSD-positive and 31 PTSD-negative male combat-exposed veterans was used for validation of these findings (‘Test group’). Plasma metabolite profiles were measured in all subjects using ultrahigh performance liquid chromatography/tandem mass spectrometry and gas chromatography/mass spectrometry. We identified key differences between PTSD subjects and controls in pathways related to glycolysis and fatty acid uptake and metabolism in the initial ‘Discovery group’, consistent with mitochondrial alterations or dysfunction, which were also confirmed in the ‘Test group’. Other pathways related to urea cycle and amino acid metabolism were different between PTSD subjects and controls in the ‘Discovery’ but not in the smaller ‘Test’ group. These metabolic differences were not explained by comorbid major depression, body mass index, blood glucose, hemoglobin A1c, smoking, or use of analgesics, antidepressants, statins, or anti-inflammatories. These data show replicable, wide-ranging changes in the metabolic profile of combat-exposed males with PTSD, with a suggestion of mitochondrial alterations or dysfunction, that may contribute to the behavioral and somatic phenotypes associated with this disease.
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Affiliation(s)
- Synthia H. Mellon
- Department of Obstetrics, Gynecology & Reproductive Sciences, University of California, San Francisco, CA, United States of America
- * E-mail:
| | - F. Saverio Bersani
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
| | - Daniel Lindqvist
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
| | - Rasha Hammamieh
- Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, United States of America
| | - Duncan Donohue
- Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, United States of America
| | - Kelsey Dean
- School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States of America
| | - Marti Jett
- Integrative Systems Biology, US Army Medical Research and Materiel Command, USACEHR, Fort Detrick, Frederick, MD, United States of America
| | - Rachel Yehuda
- Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Janine Flory
- Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Victor I. Reus
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
| | - Linda M. Bierer
- Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Iouri Makotkine
- Department of Psychiatry, James J. Peters VA Medical Center, Bronx, NY and Department of Psychiatry, Icahn School of Medicine at Mount Sinai, New York, NY, United States of America
| | - Duna Abu Amara
- Department of Psychiatry, New York University Langone Medical School, New York, NY, United States of America
| | - Clare Henn Haase
- Department of Psychiatry, New York University Langone Medical School, New York, NY, United States of America
| | - Michelle Coy
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
| | - Francis J. Doyle
- School of Engineering and Applied Sciences, Harvard University, Cambridge, MA, United States of America
| | - Charles Marmar
- Department of Psychiatry, New York University Langone Medical School, New York, NY, United States of America
- Stephen and Alexandra Cohen Veteran Center for Posttraumatic Stress and Traumatic Brain Injury, New York, NY, United States of America
| | - Owen M. Wolkowitz
- Department of Psychiatry and UCSF Weill Institute for Neurosciences, University of California, San Francisco, CA, United States of America
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Overview of genomics and post-genomics research on type 2 diabetes mellitus: Future perspectives and a framework for further studies. J Biosci 2019. [DOI: 10.1007/s12038-018-9818-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Dong M, Ren M, Li C, Zhang X, Yang C, Zhao L, Gao H. Analysis of Metabolic Alterations Related to Pathogenic Process of Diabetic Encephalopathy Rats. Front Cell Neurosci 2019; 12:527. [PMID: 30692917 PMCID: PMC6339875 DOI: 10.3389/fncel.2018.00527] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2018] [Accepted: 12/19/2018] [Indexed: 12/25/2022] Open
Abstract
Diabetic encephalopathy (DE) is a diabetic complication characterized by alterations in cognitive function and nervous system structure. The pathogenic transition from hyperglycemia to DE is a long-term process accompanied by multiple metabolic disorders. Exploring time-dependent metabolic changes in hippocampus will facilitate our understanding of the pathogenesis of DE. In the present study, we first performed behavioral and histopathological experiments to confirm the appearance of DE in rats with streptozotocin-induced diabetes. We then utilized nuclear magnetic resonance-based metabonomics to analyze metabolic disorders in the hippocampus at different stages of DE. After 1 week, we observed no cognitive or structural impairments in diabetic rats, although some metabolic changes were observed in local hippocampal extracts. At 5 weeks, while cognitive function was still normal, we then examined initial levels of neuronal apoptosis. The characteristic metabolic changes of this stage included elevated levels of energy metabolites (i.e., ATP, ADP, AMP, and creatine phosphate/creatine). At 9 weeks, significant cognitive decline and histopathological brain damage were observed, in conjunction with reduced levels of some amino acids. Thus, this stage was classified as the DE period. Our findings indicated that the pathogenesis of DE is associated with time-dependent alterations in metabolic features in hippocampal regions, such as glycolysis, osmoregulation, energy metabolism, choline metabolism, branched-chain amino acid metabolism, and the glutamate-glutamine cycle. Furthermore, we observed alterations in levels of lactate and its receptor in hippocampal cells, which may be involved in the pathogenesis of DE.
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Affiliation(s)
- Minjian Dong
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Mengqian Ren
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Chen Li
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Xi Zhang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Changwei Yang
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Liangcai Zhao
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
| | - Hongchang Gao
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou, China
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31
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Wang S, Wang J, Zhang R, Zhao A, Zheng X, Yan D, Jiang F, Jia W, Hu C, Jia W. Association between serum haptoglobin and carotid arterial functions: usefulness of a targeted metabolomics approach. Cardiovasc Diabetol 2019; 18:8. [PMID: 30634984 PMCID: PMC6329046 DOI: 10.1186/s12933-019-0808-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/23/2018] [Accepted: 01/03/2019] [Indexed: 01/21/2023] Open
Abstract
Background Serum haptoglobin (Hp) has been closely associated with cardio-cerebrovascular diseases. We investigated a metabolic profile associated with circulating Hp and carotid arterial functions via a targeted metabolomics approach to provide insight into potential mechanisms. Methods A total of 240 participants, including 120 patients with type 2 diabetes mellitus (T2DM) and 120 non-diabetes mellitus (non-DM) subjects were recruited in this study. Targeted metabolic profiles of serum metabolites were determined using an AbsoluteIDQ™ p180 Kit (BIOCRATES Life Sciences AG, Innsbruck, Austria). Ultrasound of the bilateral common carotid artery was used to measure intima-media thickness and inter-adventitial diameter. Serum Hp levels were tested by enzyme-linked immunosorbent assay. Results Serum Hp levels in T2DM patients and non-DM subjects were 103.40 (72.46, 131.99) mg/dL and 100.20 (53.99, 140.66) mg/dL, respectively. Significant differences of 19 metabolites and 17 metabolites were found among serum Hp tertiles in T2DM patients and non-DM subjects, respectively (P < 0.05). Of these, phosphatidylcholine acyl-alkyl C32:2 (PC ae C32:2) was the common metabolite observed in two populations, which was associated with the serum Hp groups and lipid traits (P < 0.05). Furthermore, the metabolite ratios of two acidic amino acids, including aspartate to PC ae C32:2 (Asp/PC ae C32:2) and glutamate to PC ae C32:2 (Glu/PC ae C32:2) were correlated with serum Hp, carotid arterial functions and other biochemical index in both populations significantly (P < 0.05). Conclusions Targeted metabolomics analyses might provide a new insight into the potential mechanisms underlying the association between serum Hp and carotid arterial functions. Electronic supplementary material The online version of this article (10.1186/s12933-019-0808-2) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Shiyun Wang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China
| | - Jie Wang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China
| | - Rong Zhang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China
| | - Aihua Zhao
- Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China
| | - Xiaojiao Zheng
- Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China
| | - Dandan Yan
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China
| | - Feng Jiang
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China
| | - Wei Jia
- Center for Translational Medicine, Shanghai Key Laboratory of Diabetes Mellitus, Department of Endocrinology and Metabolism, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China
| | - Cheng Hu
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China. .,Institute for Metabolic Disease, Fengxian Central Hospital Affiliated to Southern Medical University, 6600 Nanfeng Road, Shanghai, 201499, People's Republic of China.
| | - Weiping Jia
- Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai Clinical Center for Diabetes, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, 600 Yishan Road, Shanghai, 200233, People's Republic of China.
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Zhao L, Dong M, Ren M, Li C, Zheng H, Gao H. Metabolomic Analysis Identifies Lactate as an Important Pathogenic Factor in Diabetes-associated Cognitive Decline Rats. Mol Cell Proteomics 2018; 17:2335-2346. [PMID: 30171160 PMCID: PMC6283288 DOI: 10.1074/mcp.ra118.000690] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Revised: 08/19/2018] [Indexed: 12/23/2022] Open
Abstract
Diabetes mellitus causes brain structure changes and cognitive decline, and it has been estimated that diabetes doubles the risk for dementia. Until now, the pathogenic mechanism of diabetes-associated cognitive decline (DACD) has remained unclear. Using metabolomics, we show that lactate levels increased over time in the hippocampus of rats with streptozotocin-induced diabetes, as compared with age-matched control rats. Additionally, mRNA levels, protein levels, and enzymatic activity of lactate dehydrogenase-A (LDH-A) were significantly up-regulated, suggesting increased glycolysis activity. Importantly, by specifically blocking the glycolysis pathway through an LDH-A inhibitor, chronic diabetes-induced memory impairment was prevented. Analyzing the underlying mechanism, we show that the expression levels of cAMP-dependent protein kinase and of phosphorylated transcription factor cAMP response element-binding proteins were decreased in 12-week diabetic rats. We suggest that G protein-coupled receptor 81 mediates cognitive decline in the diabetic rat. In this study, we report that progressively increasing lactate levels is an important pathogenic factor in DACD, directly linking diabetes to cognitive dysfunction. LDH-A may be considered as a potential target for alleviating or treating DACD in the future.
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Affiliation(s)
- Liangcai Zhao
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Minjian Dong
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Mengqian Ren
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Chen Li
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Hong Zheng
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China
| | - Hongchang Gao
- School of Pharmaceutical Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang, China.
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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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34
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Progress in Metabonomics of Type 2 Diabetes Mellitus. Molecules 2018; 23:molecules23071834. [PMID: 30041493 PMCID: PMC6100487 DOI: 10.3390/molecules23071834] [Citation(s) in RCA: 31] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2018] [Revised: 07/18/2018] [Accepted: 07/19/2018] [Indexed: 12/20/2022] Open
Abstract
With the improvement of living standards and a change in lifestyle, the incidence of type 2 diabetes mellitus (T2DM) is increasing. Its etiology is too complex to be completely understand yet. Metabonomics techniques are used to study the changes of metabolites and metabolic pathways before and after the onset of diabetes and make it more possible to further understand the pathogenesis of T2DM and improve its prediction, early diagnosis, and treatment. In this review, we summarized the metabonomics study of T2DM in recent years and provided a theoretical basis for the study of pathogenesis and the effective prevention and treatment of T2DM.
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Wan W, Li H, Xiang J, Yi F, Xu L, Jiang B, Xiao P. Aqueous Extract of Black Maca Prevents Metabolism Disorder via Regulating the Glycolysis/Gluconeogenesis-TCA Cycle and PPARα Signaling Activation in Golden Hamsters Fed a High-Fat, High-Fructose Diet. Front Pharmacol 2018; 9:333. [PMID: 29681858 PMCID: PMC5897445 DOI: 10.3389/fphar.2018.00333] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/01/2018] [Accepted: 03/22/2018] [Indexed: 12/19/2022] Open
Abstract
Maca (Lepidium meyenii Walpers) has been used as a dietary supplement and ethnomedicine for centuries. Recently, maca has become a high profile functional food worldwide because of its multiple biological activities. This study is the first explorative research to investigate the prevention and amelioration capacity of the aqueous extract of black maca (AEM) on high-fat, high-fructose diet (HFD)-induced metabolism disorder in golden hamsters and to identify the potential mechanisms involved in these effects. For 20 weeks, 6-week-old male golden hamsters were fed the following respective diets: (1) a standard diet, (2) HFD, (3) HFD supplemented with metformin, or (4) HFD supplemented with three doses of AEM (300, 600, or 1,200 mg/kg). After 20 weeks, the golden hamsters that received daily AEM supplementation presented with the beneficial effects of improved hyperlipidemia, hyperinsulinemia, insulin resistance, and hepatic steatosis in vivo. Based on the hepatic metabolomic analysis results, alterations in metabolites associated with pathological changes were examined. A total of 194 identified metabolites were mapped to 46 relative metabolic pathways, including those of energy metabolism. In addition, via in silico profiling for secondary maca metabolites by a joint pharmacophore- and structure-based approach, a compound-target-disease network was established. The results revealed that 32 bioactive compounds in maca targeted 16 proteins involved in metabolism disorder. Considering the combined metabolomics and virtual screening results, we employed quantitative real-time PCR assays to verify the gene expression of key enzymes in the relevant pathways. AEM promoted glycolysis and inhibited gluconeogenesis via regulating the expression of key genes such as Gck and Pfkm. Moreover, AEM upregulated tricarboxylic acid (TCA) cycle flux by changing the concentrations of intermediates and increasing the mRNA levels of Aco2, Fh, and Mdh2. In addition, the lipid-lowering effects of AEM in boththe serum and liver may be partly related to PPARα signaling activation, including enhanced fatty acid β-oxidation and lipogenesis pathway inhibition. Together, our data demonstrated that AEM intervention significantly improved lipid and glucose metabolism disorder by regulating the glycolysis/gluconeogenesis-TCA cycle and by modulating gene expression levels involved in the PPARα signaling pathway.
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Affiliation(s)
- Wenting Wan
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China
| | - Hongxiang Li
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China
| | - Jiamei Xiang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China
| | - Fan Yi
- School of Sciences/Key Laboratory of Cosmetic, China National Light Industry, Beijing Technology and Business University, Beijing, China
| | - Lijia Xu
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China
| | - Baoping Jiang
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China
| | - Peigen Xiao
- Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.,Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine, Ministry of Education, Beijing, China
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Jacob SI, Murray KJ, Rendahl AK, Geor RJ, Schultz NE, McCue ME. Metabolic perturbations in Welsh Ponies with insulin dysregulation, obesity, and laminitis. J Vet Intern Med 2018; 32:1215-1233. [PMID: 29572947 PMCID: PMC5980341 DOI: 10.1111/jvim.15095] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2017] [Revised: 12/05/2017] [Accepted: 02/13/2018] [Indexed: 01/05/2023] Open
Abstract
Background Metabolomics, the study of small‐molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS). Objectives (1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis. Animals Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non‐insulin dysregulated [CON] (n = 10, insulin < 30 mU/L) or insulin dysregulated [ID] (n = 10, insulin > 60 mU/L) at 75 minutes after administration of Karo syrup, obese (n = 6) or nonobese (n = 14), and history of laminitis (n = 9) or no history of laminitis (n = 11). Methods Case‐control study. Metabolomic analysis was performed on serum obtained at 0 minutes (baseline) and 75 minutes during the OST. Data were analyzed with multivariable mixed linear models with significance set at P ≤ .05. Results Metabolomic analysis of 646 metabolites (506 known) detected significant metabolite differences. At baseline, 55 metabolites (insulin response), 91 metabolites (obesity status), and 136 metabolites (laminitis history) were different. At 75 minutes, 51 metabolites (insulin response), 102 metabolites (obesity status), and 124 metabolites (laminitis history) were different. Conclusions and Clinical Importance Use of metabolomics could have diagnostic utility for early detection of EMS and provide new knowledge regarding the pathophysiology of metabolic perturbations associated with this condition that might lead to improved clinical management.
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Affiliation(s)
- Sarah I Jacob
- Michigan State University College of Veterinary Medicine, Large Animal Clinical Sciences, East Lansing, Michigan
| | - Kevin J Murray
- University of Minnesota College of Veterinary Medicine, Veterinary Population Medicine, St. Paul, Minnesota
| | - Aaron K Rendahl
- University of Minnesota College of Veterinary Medicine, Veterinary Population Medicine, St. Paul, Minnesota
| | - Raymond J Geor
- Massey University College of Sciences, Palmerston North, New Zealand
| | - Nichol E Schultz
- University of Minnesota College of Veterinary Medicine, Veterinary Population Medicine, St. Paul, Minnesota
| | - Molly E McCue
- University of Minnesota College of Veterinary Medicine, Veterinary Population Medicine, St. Paul, Minnesota
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37
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Zhao G, Hou X, Li X, Qu M, Tong C, Li W. Metabolomics analysis of alloxan-induced diabetes in mice using UPLC–Q-TOF-MS after Crassostrea gigas polysaccharide treatment. Int J Biol Macromol 2018; 108:550-557. [DOI: 10.1016/j.ijbiomac.2017.12.057] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2017] [Revised: 12/07/2017] [Accepted: 12/07/2017] [Indexed: 01/12/2023]
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38
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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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Van Meulebroek L, De Paepe E, Vercruysse V, Pomian B, Bos S, Lapauw B, Vanhaecke L. Holistic Lipidomics of the Human Gut Phenotype Using Validated Ultra-High-Performance Liquid Chromatography Coupled to Hybrid Orbitrap Mass Spectrometry. Anal Chem 2017; 89:12502-12510. [DOI: 10.1021/acs.analchem.7b03606] [Citation(s) in RCA: 35] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Affiliation(s)
- Lieven Van Meulebroek
- Laboratory
of Chemical Analysis, Department of Veterinary Public Health and Food
Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan
133, 9820 Merelbeke, Belgium
| | - Ellen De Paepe
- Laboratory
of Chemical Analysis, Department of Veterinary Public Health and Food
Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan
133, 9820 Merelbeke, Belgium
| | - Vicky Vercruysse
- Laboratory
of Chemical Analysis, Department of Veterinary Public Health and Food
Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan
133, 9820 Merelbeke, Belgium
| | - Beata Pomian
- Laboratory
of Chemical Analysis, Department of Veterinary Public Health and Food
Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan
133, 9820 Merelbeke, Belgium
| | | | | | - Lynn Vanhaecke
- Laboratory
of Chemical Analysis, Department of Veterinary Public Health and Food
Safety, Faculty of Veterinary Medicine, Ghent University, Salisburylaan
133, 9820 Merelbeke, Belgium
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40
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Metabolomics applied to diabetes-lessons from human population studies. Int J Biochem Cell Biol 2017; 93:136-147. [PMID: 29074437 DOI: 10.1016/j.biocel.2017.10.011] [Citation(s) in RCA: 24] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2017] [Revised: 09/30/2017] [Accepted: 10/20/2017] [Indexed: 02/08/2023]
Abstract
The 'classical' distribution of type 2 diabetes (T2D) across the globe is rapidly changing and it is no longer predominantly a disease of middle-aged/elderly adults of western countries, but it is becoming more common through Asia and the Middle East, as well as increasingly found in younger individuals. This global altered incidence of T2D is most likely associated with the spread of western diets and sedentary lifestyles, although there is still much debate as to whether the increased incidence rates are due to an overconsumption of fats, sugars or more generally high-calorie foods. In this context, understanding the interactions between genes of risk and diet and how they influence the incidence of T2D will help define the causative pathways of the disease. This review focuses on the use of metabolomics in large cohort studies to follow the incidence of type 2 diabetes in different populations. Such approaches have been used to identify new biomarkers of pre-diabetes, such as branch chain amino acids, and associate metabolomic profiles with genes of known risk in T2D from large scale GWAS studies. As the field develops, there are also examples of meta-analysis across metabolomics cohort studies and cross-comparisons with different populations to allow us to understand how genes and diet contribute to disease risk. Such approaches demonstrate that insulin resistance and T2D have far reaching metabolic effects beyond raised blood glucose and how the disease impacts systemic metabolism.
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41
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Gong P, Chang X, Chen X, Bai X, Wen H, Pi S, Yang W, Wang L, Chen F. Metabolomics study of cadmium-induced diabetic nephropathy and protective effect of caffeic acid phenethyl ester using UPLC-Q-TOF-MS combined with pattern recognition. ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY 2017; 54:80-92. [PMID: 28704754 DOI: 10.1016/j.etap.2017.06.021] [Citation(s) in RCA: 29] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/29/2017] [Revised: 05/16/2017] [Accepted: 06/21/2017] [Indexed: 06/07/2023]
Abstract
Diabetic nephropathy (DN) is the most severe complication of diabetes and multiple factors are involved in the pathogenesis of DN. Among them, cadmium (Cd) acts as a risk factor inducing the occurrence of DN. The present study focused on investigating the protective role of caffeic acid phenethyl ester (CAPE), an active component of propolis from honeybee hives, against Cd-induced DN in mice based on ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS)and pattern recognition. Serum and urine biochemical indexes were detected and histopathological observation has been done to evaluate the damage of Cd on animals. Moreover, the global serum profiles of different groups were distinguished by UPLC-Q-TOF-MS and principal component analysis (PCA) were applied for group differentiation and marker selection. Moreover, the influence of Cd on the oxidative status in DN mice were also evaluated by assessing the parameters of oxidative stress, proinflammatory cytokines and antioxidant competence. As shown in the scores plots, the distinct clustering among controls, DN and CAPE groups were observed, significant changes in serum levels of LysoPC(18:1(11Z)), 2,3-dinor-8-iso-PGF2a, PS(18:1(9Z)/18:1(9Z)), DG(17:0/22:4 (7Z,10Z, 13Z, 16Z)/0:0) and Arachidonic acid(AA) were noted and identified as potential biomarkers, the effect of CAPE reverted them back to near normalcy. Further, It was observed a significant improvement in lipid peroxides (LPO) and protein carbonyls (PCO) levels in Cd-induced DN kidneys along with a significant decline in superoxide dismutase (SOD), catalase (CAT), and reduced glutathione (GSH) levels, however, CAPE relieved these changes. In conclusion, the study suggested that the pathogenesis of DN caused by Cd probably owes to the perturbations of lipid metabolism and AA metabolism; CAPE seems to be effective agent and may be related to its potent antioxidant, anti-inflammatory properties and action as an Nrf2 activator.
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Affiliation(s)
- Pin Gong
- College of Food and Biotechnology, Shaanxi University of Science and Technology, Xi'an, 710021, China
| | - Xiangna Chang
- College of Food and Biotechnology, Shaanxi University of Science and Technology, Xi'an, 710021, China
| | - Xuefeng Chen
- College of Food and Biotechnology, Shaanxi University of Science and Technology, Xi'an, 710021, China
| | - Xiaohuan Bai
- College of Food and Biotechnology, Shaanxi University of Science and Technology, Xi'an, 710021, China
| | - He Wen
- College of Food and Biotechnology, Shaanxi University of Science and Technology, Xi'an, 710021, China
| | - Sihui Pi
- College of Food and Biotechnology, Shaanxi University of Science and Technology, Xi'an, 710021, China
| | - Wenjuan Yang
- College of Food and Biotechnology, Shaanxi University of Science and Technology, Xi'an, 710021, China
| | - Lan Wang
- College of Food and Biotechnology, Shaanxi University of Science and Technology, Xi'an, 710021, China
| | - Fuxin Chen
- School of Chemistry and Chemical Engineering, Xi'an University of Science and Technology, Xi'an, 710054, China.
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Hu Q, Wei J, Liu Y, Fei X, Hao Y, Pei D, Di D. Discovery and identification of potential biomarkers for alcohol-induced oxidative stress based on cellular metabolomics. Biomed Chromatogr 2017; 31. [PMID: 27925248 DOI: 10.1002/bmc.3907] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2016] [Revised: 11/15/2016] [Accepted: 11/27/2016] [Indexed: 01/28/2023]
Abstract
Biomarkers involved in alcohol-induced oxidative stress play an important role in alcoholic liver disease prevention and diagnosis. Alcohol-induced oxidative stress in human liver L-02 cells was used to discover the potential biomarkers. Metabolites from L-02 cells induced by alcohol were measured by high-performance liquid chromatography and mass spectrometry. Fourteen metabolites that allowed discrimination between control and model groups were discovered by multivariate statistical data analysis (i.e. principal components analysis, orthogonal partial least-squares discriminate analysis). Based on the retention time, UV spectrum and LC-MS findings of the samples and compared with the authentic standards, eight biomarkers involved in alcohol-induced oxidative stress, namely, malic acid, oxidized glutathione, γ-glutamyl-cysteinyl-glycine, adenosine triphosphate, phenylalanine, adenosine monophosphate, nitrotyrosine and tryptophan, were identified. These biomarkers offered important targets for disease diagnosis and other researches.
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Affiliation(s)
- Qingping Hu
- Institute of Nutrition and Food Hygiene, School of Public Health, Lanzhou University, Lanzhou, China.,Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, China.,Center of Resource Chemical and New Material, Qingdao, China
| | - Jianteng Wei
- Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, China.,Center of Resource Chemical and New Material, Qingdao, China
| | - Yewei Liu
- Institute of Nutrition and Food Hygiene, School of Public Health, Lanzhou University, Lanzhou, China
| | - Xiulan Fei
- Institute of Nutrition and Food Hygiene, School of Public Health, Lanzhou University, Lanzhou, China
| | - Yuwei Hao
- Institute of Nutrition and Food Hygiene, School of Public Health, Lanzhou University, Lanzhou, China
| | - Dong Pei
- Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, China.,Center of Resource Chemical and New Material, Qingdao, China
| | - Duolong Di
- Key Laboratory of Chemistry of Northwestern Plant Resources and Key Laboratory for Natural Medicine of Gansu Province, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences, Lanzhou, China.,Center of Resource Chemical and New Material, Qingdao, China
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Lu Y, Chen C. Metabolomics: Bridging Chemistry and Biology in Drug Discovery and Development. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/s40495-017-0083-4] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
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Abstract
SIGNIFICANCE Reactive oxygen species (ROS) reactive nitrogen species (RNS) and redox processes are of key importance in obesity- and diabetes-related kidney disease; however, there remains significant controversy in the field. RECENT ADVANCES New data from imaging and in vivo models of obesity and diabetic kidney disease have shed new insights into this field. In the setting of obesity- and diabetes-related kidney injury, there is a growing recognition that the major moieties of ROS and RNS are hydrogen peroxide and peroxynitrite with the enzymatic sources being NADPH oxidases and nitric oxide synthase, respectively. However, the role of mitochondrial superoxide as a driver of renal complications remains unclear. CRITICAL ISSUES Several key issues that are often not discussed are the specific ROS and RNS molecules, the source of generation, the location of production, and downstream targets. FUTURE DIRECTIONS Further understanding of the role of ROS/RNS/redox and their relationship with key signaling and metabolic pathways such as AMP-activated protein kinase (AMPK) and hypoxia-inducible factor 1-α (HIF1α) will be critical to a new understanding of kidney complications of caloric challenges and new therapeutic approaches. Antioxid. Redox Signal. 25, 208-216.
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Affiliation(s)
- Kumar Sharma
- 1 Center for Renal Translational Medicine, Institute of Metabolomic Medicine, University of California San Diego , La Jolla, California.,2 Division of Nephrology-Hypertension, Veterans Affairs San Diego Healthcare System , La Jolla, California
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Zhao X, Gang X, Liu Y, Sun C, Han Q, Wang G. Using Metabolomic Profiles as Biomarkers for Insulin Resistance in Childhood Obesity: A Systematic Review. J Diabetes Res 2016; 2016:8160545. [PMID: 27517054 PMCID: PMC4969529 DOI: 10.1155/2016/8160545] [Citation(s) in RCA: 47] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2016] [Revised: 05/28/2016] [Accepted: 06/15/2016] [Indexed: 12/21/2022] Open
Abstract
A growing body of evidence has shown the intimate relationship between metabolomic profiles and insulin resistance (IR) in obese adults, while little is known about childhood obesity. In this review, we searched available papers addressing metabolomic profiles and IR in obese children from inception to February 2016 on MEDLINE, Web of Science, the Cochrane Library, ClinicalTrials.gov, and EMASE. HOMA-IR was applied as surrogate markers of IR and related metabolic disorders at both baseline and follow-up. To minimize selection bias, two investigators independently completed this work. After critical selection, 10 studies (including 2,673 participants) were eligible and evaluated by using QUADOMICS for quality assessment. Six of the 10 studies were classified as "high quality." Then we generated all the metabolites identified in each study and found amino acid metabolism and lipid metabolism were the main affected metabolic pathways in obese children. Among identified metabolites, branched-chain amino acids (BCAAs), aromatic amino acids (AAAs), and acylcarnitines were reported to be associated with IR as biomarkers most frequently. Additionally, BCAAs and tyrosine seemed to be relevant to future metabolic risk in the long-term follow-up cohorts, emphasizing the importance of early diagnosis and prevention strategy. Because of limited scale and design heterogeneity of existing studies, future studies might focus on validating above findings in more large-scale and longitudinal studies with elaborate design.
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Affiliation(s)
- Xue Zhao
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, China
| | - Xiaokun Gang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, China
| | - Yujia Liu
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, China
| | - Chenglin Sun
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, China
| | - Qing Han
- Hospital of Orthopedics, The Second Hospital of Jilin University, Changchun 130021, China
| | - Guixia Wang
- Department of Endocrinology and Metabolism, The First Hospital of Jilin University, Changchun 130021, China
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46
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Nikolic SB, Edwards LM, Karpievitch YV, Wilson R, Horne J, Adams MJ, Sharman JE. Serum metabolic profile predicts adverse central haemodynamics in patients with type 2 diabetes mellitus. Acta Diabetol 2016; 53:367-75. [PMID: 26338006 DOI: 10.1007/s00592-015-0802-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2015] [Accepted: 07/24/2015] [Indexed: 01/19/2023]
Abstract
AIMS People with type 2 diabetes mellitus (T2DM) have abnormal peripheral and central haemodynamics at rest and during exercise, probably due to metabolic perturbations, but mechanisms are unknown. We used untargeted metabolomics to determine the relationships between metabolic perturbations and haemodynamics (peripheral and central) measured at rest and during exercise. METHODS Serum samples from 39 participants with T2DM (62 ± 9 years; 46 % male) and 39 controls (52 ± 10 years; 51 % male) were analysed by liquid chromatography-mass spectrometry, nuclear magnetic resonance spectroscopy and principal component analysis. Scores on principal components (PC) were used to assess relationships with haemodynamics including peripheral and central BP, central augmentation index (AIx) and central augmentation pressure (AP). RESULTS Participants with T2DM had higher resting and exercise haemodynamics (peripheral and central BP, central AIx and central AP) compared to controls (p < 0.05). PC that comprised of a signature metabolic pattern of T2DM was independently associated with resting and exercise central AIx and central AP (p < 0.05). CONCLUSIONS Serum metabolic profile was associated with central, but not peripheral, haemodynamics in T2DM participants, suggesting that metabolic irregularities may explain abnormal central haemodynamics in T2DM patients.
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Affiliation(s)
- Sonja B Nikolic
- Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, 7000, Australia
| | - Lindsay M Edwards
- Centre of Human and Aerospace Physiological Sciences, King's College London, London, UK.
- Fibrosis Discovery Performance Unit, GSK Medicines Research Centre, GlaxoSmithKline R&D, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
| | | | - Richard Wilson
- Central Science Laboratory, University of Tasmania, Hobart, Australia
| | - James Horne
- Central Science Laboratory, University of Tasmania, Hobart, Australia
| | - Murray J Adams
- School of Health Sciences, University of Tasmania, Launceston, Australia
| | - James E Sharman
- Menzies Institute for Medical Research, University of Tasmania, 17 Liverpool Street, Hobart, 7000, Australia.
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47
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Gerö D, Szabo C. Glucocorticoids Suppress Mitochondrial Oxidant Production via Upregulation of Uncoupling Protein 2 in Hyperglycemic Endothelial Cells. PLoS One 2016; 11:e0154813. [PMID: 27128320 PMCID: PMC4851329 DOI: 10.1371/journal.pone.0154813] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2015] [Accepted: 04/19/2016] [Indexed: 11/19/2022] Open
Abstract
Diabetic complications are the leading cause of morbidity and mortality in diabetic patients. Elevated blood glucose contributes to the development of endothelial and vascular dysfunction, and, consequently, to diabetic micro- and macrovascular complications, because it increases the mitochondrial proton gradient and mitochondrial oxidant production. Therapeutic approaches designed to counteract glucose-induced mitochondrial reactive oxygen species (ROS) production in the vasculature are expected to show efficacy against all diabetic complications, but direct pharmacological targeting (scavenging) of mitochondrial oxidants remains challenging due to the high reactivity of some of these oxidant species. In a recent study, we have conducted a medium-throughput cell-based screening of a focused library of well-annotated pharmacologically active compounds and identified glucocorticoids as inhibitors of mitochondrial superoxide production in microvascular endothelial cells exposed to elevated extracellular glucose. The goal of the current study was to investigate the mechanism of glucocorticoids' action. Our findings show that glucocorticoids induce the expression of the mitochondrial UCP2 protein and decrease the mitochondrial potential. UCP2 silencing prevents the protective effect of the glucocorticoids on ROS production. UCP2 induction also increases the oxygen consumption and the "proton leak" in microvascular endothelial cells. Furthermore, glutamine supplementation augments the effect of glucocorticoids via further enhancing the expression of UCP2 at the translational level. We conclude that UCP2 induction represents a novel experimental therapeutic intervention in diabetic vascular complications. While direct repurposing of glucocorticoids may not be possible for the therapy of diabetic complications due to their significant side effects that develop during chronic administration, the UCP2 pathway may be therapeutically targetable by other, glucocorticoid-independent pharmacological means.
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Affiliation(s)
- Domokos Gerö
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America
- University of Exeter Medical School, Exeter, United Kingdom
- * E-mail:
| | - Csaba Szabo
- Department of Anesthesiology, University of Texas Medical Branch, Galveston, Texas, United States of America
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48
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Geamanu A, Gupta SV, Bauerfeld C, Samavati L. Metabolomics connects aberrant bioenergetic, transmethylation, and gut microbiota in sarcoidosis. Metabolomics 2016; 12:35. [PMID: 27489531 PMCID: PMC4960975 DOI: 10.1007/s11306-015-0932-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
Sarcoidosis is a systemic granulomatous disease of unknown etiology. Granulomatous inflammation in sarcoidosis may affect multiple organs, including the lungs, skin, CNS, and the eyes, leading to severe morbidity and mortality. The underlying mechanisms for sustained inflammation in sarcoidosis are unknown. We hypothesized that metabolic changes play a critical role in perpetuation of inflammation in sarcoidosis. 1H nuclear magnetic resonance (NMR)-based untargeted metabolomic analysis was used to identify circulating molecules in serum to discriminate sarcoidosis patients from healthy controls. Principal component analyses (PCA) were performed to identify different metabolic markers and explore the changes of associated biochemical pathways. Using Chenomx 7.6 NMR Suite software, we identified and quantified metabolites responsible for such separation in the PCA models. Quantitative analysis showed that the levels of metabolites, such as 3-hydroxybutyrate, acetoacetate, carnitine, cystine, homocysteine, pyruvate, and trimethylamine N-oxide were significantly increased in sarcoidosis patients. Interestingly, succinate, a major intermediate metabolite involved in the tricyclic acid cycle was significantly decreased in sarcoidosis patients. Application of integrative pathway analyses identified deregulation of butanoate, ketone bodies, citric cycle metabolisms, and transmethylation. This may be used for development of new drugs or nutritional modification.
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Affiliation(s)
- Andreea Geamanu
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine and Detroit Medical Center, 3990 John R., 3 Hudson, Detroit, MI 48201, USA
| | - Smiti V. Gupta
- Department of Nutrition and Food Science, Wayne State University, Detroit, MI 48201, USA
| | - Christian Bauerfeld
- Division of Pediatric Critical Care, Department of Pediatrics, Children’s Hospital of Michigan, Detroit, MI 48201, USA
| | - Lobelia Samavati
- Division of Pulmonary, Allergy, Critical Care and Sleep Medicine, Department of Medicine, Wayne State University School of Medicine and Detroit Medical Center, 3990 John R., 3 Hudson, Detroit, MI 48201, USA
- Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI 48201, USA
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49
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den Ouden H, Pellis L, Rutten GEHM, Geerars-van Vonderen IK, Rubingh CM, van Ommen B, van Erk MJ, Beulens JWJ. Metabolomic biomarkers for personalised glucose lowering drugs treatment in type 2 diabetes. Metabolomics 2016; 12:27. [PMID: 26770180 PMCID: PMC4703625 DOI: 10.1007/s11306-015-0930-4] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/01/2015] [Accepted: 10/17/2015] [Indexed: 02/06/2023]
Abstract
We aimed to identify metabolites to predict patients' response to glucose lowering treatment during the first 5 years after detection of type 2 diabetes. Metabolites were measured by GC-MS in baseline samples from 346 screen-detected type 2 diabetes patients in the ADDITION-NL study. The response to treatment with metformin and/or sulphonylurea (SU) was analysed to identify metabolites predictive of 5 year HbA1c change by multiple regression analysis. Baseline glucose and 1,5 anhydro-glucitol were associated with HbA1c decrease in all medication groups. In patients on SU no other metabolite was associated with HbA1c decrease. A larger set of metabolites was associated with HbA1c change in the metformin and the combination therapy (metformin + SU) groups. These metabolites included metabolites related to liver metabolism, such as 2-hydroxybutanoic acid, 3-hydroxybutanoic acid, 2-hydroxypiperidine and 4-oxoproline). Metabolites involved in oxidative stress and insulin resistance were higher when the HbA1c decrease was larger in the metformin/sulphonylurea group. The associations between baseline metabolites and responsiveness to medication are in line with its mode of action. If these results could be replicated in other populations, the most promising predictive candidates might be tested to assess whether they could enhance personalised treatment.
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Affiliation(s)
- Henk den Ouden
| | - Linette Pellis
| | - Guy E. H. M. Rutten
| | | | - Carina M. Rubingh
| | - Ben van Ommen
| | - Marjan J. van Erk
| | - Joline W. J. Beulens
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50
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Yu D, Moore SC, Matthews CE, Xiang YB, Zhang X, Gao YT, Zheng W, Shu XO. Plasma metabolomic profiles in association with type 2 diabetes risk and prevalence in Chinese adults. Metabolomics 2016; 12:3. [PMID: 27840598 PMCID: PMC5102259 DOI: 10.1007/s11306-015-0890-8] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Metabolomic studies have identified several metabolites associated with type 2 diabetes (T2D) in populations of European ancestry. East Asians, a population of particular susceptibility to T2D, were generally not included in previous studies. We examined the associations of plasma metabolites with risk and prevalence of T2D in 976 Chinese men and women (40-74 years of age) who were participants of two prospective cohort studies and had no cardiovascular disease or cancer at baseline. Sixty-eight prevalent and 73 incident T2D cases were included. Non-targeted metabolomics was conducted that detected 689 metabolites with known identities and 690 unknown metabolites. Multivariable logistic and Cox regressions were used to evaluate the associations of standardized metabolites with diabetes risk and prevalence. We identified 36 known metabolites and 10 unknown metabolites associated with prevalent and/or incident T2D at false discovery rate <0.05. The known metabolites are involved in metabolic pathways of glycolysis/gluconeogenesis, branched-chain amino acids, other amino acids, fatty acids, glycerophospholipids, androgen, and bradykinin. Six metabolites showed independent associations with incident T2D: 1,5-anhydroglucitol, mannose, valine, 3-methoxytyrosine, docosapentaenoate (22:5n3), and bradykinin-hydroxy-pro(3). Each standard deviation increase in these metabolites was associated with a 40-150 % change in risk of developing diabetes (30-80 % after further adjustment for glucose). Risk prediction was significantly improved by adding these metabolites in addition to known T2D risk factors, including central obesity and glucose. These findings suggest that hexoses, branched-chain amino acids, and yet to be validated novel plasma metabolites may improve risk prediction and mechanistic understanding of T2D in Chinese populations.
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Affiliation(s)
- Danxia Yu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA
| | - Steven C. Moore
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
| | - Charles E. Matthews
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD 20892, USA
| | - Yong-Bing Xiang
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200031, China
| | - Xianglan Zhang
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA
| | - Yu-Tang Gao
- Shanghai Cancer Institute, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200031, China
| | - Wei Zheng
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA
| | - Xiao-Ou Shu
- Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt University School of Medicine, 2525 West End Avenue, Suite 600, Nashville, TN 37203, USA
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