Summary of Study ST003056
This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001699. The data can be accessed directly via it's Project DOI: 10.21228/M83B08 This work is supported by NIH grant, U2C- DK119886.
See: https://www.metabolomicsworkbench.org/about/howtocite.php
This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.
| Study ID | ST003056 |
| Study Title | Untargeted metabolomics revealed multiple metabolic perturbations in plasma of T2D patients in response to Liraglutide - Part 2 |
| Study Summary | Despite the global efforts put into the clinical research and studies in order to protect against Type-2 diabetes mellitus (T2DM), the incidence of T2DM remains high causing a major health problem and impacting the health and care systems. Therefore, T2DM-related treatments and therapies are continuously invented for the clinical use, including Liraglutide. The last is a GLP-1 analogue and shows its beneficial health outcomes e.g., improved glycemic control, lower body weight, and reduced cardiovascular disease risks. The intrinsic mechanisms of these beneficial effects are not fully understood; however, our research group has previously published proteomics work demonstrating the involvement of certain important proteins in part in the beneficial health outcomes of Liraglutide. Since proteomics and metabolomics are complementary to each other in the context of the biological pathways, studying the metabolic impacts of Liraglutide on T2DM patients would add further information about the beneficial health outcomes of Liraglutide. Thus, herein, we performed an untargeted metabolomics approach for identifying metabolic pathways impacted by the treatment of Liraglutide in T2DM patients. Methods: Untargeted liquid chromatography coupled with mass spectrometry was used for metabolomics analysis of plasma samples collected from T2DM patients (n=20) before and after receiving Liraglutide treatment. Metabolic profiling and related pathway and network analyses were conducted. Results: The metabolic profiling analyses identified 93 endogenous metabolites were significantly affected by the Liraglutide treatments, which 49 metabolites up-regulated and 44 metabolites down-regulated. Moreover, the metabolic pathway analyses revealed that the most pronounced metabolite and metabolic pathways that were affected by the Liraglutide treatment was Pentose and glucuronate interconversion, suggesting the last may be a potential target of the Liraglutide treatment could be involved in part in the beneficial effects seen in T2DM patients, specially, we found that glucuronate interconversion pathway which is known by its role in eliminating toxic and undesirable substances from the human body, impacted in Liraglutide treated patients. The last findings ar consistence with our previous proteomics findings. Conclusion: These findings, taken together with our previous results, provide a deeper understanding of the underlying mechanisms involved in the beneficial effects of Liraglutide at the proteomic and metabolic levels in T2DM patients. |
| Institute | King Faisal Specialist Hospital and Research Centre (KFSHRC) |
| Last Name | Al Mogren |
| First Name | Maha |
| Address | Zahrawi Street, Al Maather, Riyadh 11211, Saudi Arabia |
| malmogren@alfaisal.edu | |
| Phone | 966541205332 |
| Submit Date | 2023-11-03 |
| Raw Data Available | Yes |
| Raw Data File Type(s) | raw(Waters) |
| Analysis Type Detail | LC-MS |
| Release Date | 2024-08-05 |
| Release Version | 1 |
Select appropriate tab below to view additional metadata details:
Project:
| Project ID: | PR001699 |
| Project DOI: | doi: 10.21228/M83B08 |
| Project Title: | Untargeted metabolomics revealed multiple metabolic perturbations in plasma of T2D patients in response to Liraglutide |
| Project Summary: | Despite the global efforts put into the clinical research and studies in order to protect against Type-2 diabetes mellitus (T2DM), the incidence of T2DM remains high causing a major health problem and impacting the health and care systems. Therefore, T2DM-related treatments and therapies are continuously invented for the clinical use, including Liraglutide. The last is a GLP-1 analogue and shows its beneficial health outcomes e.g., improved glycemic control, lower body weight, and reduced cardiovascular disease risks. The intrinsic mechanisms of these beneficial effects are not fully understood; however, our research group has previously published proteomics work demonstrating the involvement of certain important proteins in part in the beneficial health outcomes of Liraglutide. Since proteomics and metabolomics are complementary to each other in the context of the biological pathways, studying the metabolic impacts of Liraglutide on T2DM patients would add further information about the beneficial health outcomes of Liraglutide. Thus, herein, we performed an untargeted metabolomics approach for identifying metabolic pathways impacted by the treatment of Liraglutide in T2DM patients. Methods: Untargeted liquid chromatography coupled with mass spectrometry was used for metabolomics analysis of plasma samples collected from T2DM patients (n=20) before and after receiving Liraglutide treatment. Metabolic profiling and related pathway and network analyses were conducted. Results: The metabolic profiling analyses identified 93 endogenous metabolites were significantly affected by the Liraglutide treatments, which 49 metabolites up-regulated and 44 metabolites down-regulated. Moreover, the metabolic pathway analyses revealed that the most pronounced metabolite and metabolic pathways that were affected by the Liraglutide treatment was Pentose and glucuronate interconversion, suggesting the last may be a potential target of the Liraglutide treatment could be involved in part in the beneficial effects seen in T2DM patients, specially, we found that glucuronate interconversion pathway which is known by its role in eliminating toxic and undesirable substances from the human body, impacted in Liraglutide treated patients. The last findings ar consistence with our previous proteomics findings. Conclusion: These findings, taken together with our previous results, provide a deeper understanding of the underlying mechanisms involved in the beneficial effects of Liraglutide at the proteomic and metabolic levels in T2DM patients. |
| Institute: | King Faisal Specialist Hospital and Research Centre (KFSHRC) |
| Last Name: | Al Mogren |
| First Name: | Maha |
| Address: | Zahrawi Street, Al Maather, Riyadh 11211, Saudi Arabia |
| Email: | malmogren@alfaisal.edu |
| Phone: | 966541205332 |
Subject:
| Subject ID: | SU003171 |
| Subject Type: | Human |
| Subject Species: | Homo sapiens |
| Taxonomy ID: | 9606 |
| Gender: | Male |
| Species Group: | Mammals |
Factors:
Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)
| mb_sample_id | local_sample_id | Factor |
|---|---|---|
| SA331650 | V1-10 | Post-treatment |
| SA331651 | V1-11 | Post-treatment |
| SA331652 | V1-13 | Post-treatment |
| SA331653 | V1-9 | Post-treatment |
| SA331654 | V1-12 | Post-treatment |
| SA331655 | V1-7 | Post-treatment |
| SA331656 | V1-3 | Post-treatment |
| SA331657 | V1-4 | Post-treatment |
| SA331658 | V1-6 | Post-treatment |
| SA331659 | V1-14 | Post-treatment |
| SA331660 | V1-8 | Post-treatment |
| SA331661 | V1-15 | Post-treatment |
| SA331662 | V1-21 | Post-treatment |
| SA331663 | V1-22 | Post-treatment |
| SA331664 | V1-25 | Post-treatment |
| SA331665 | V1-28 | Post-treatment |
| SA331666 | V1-20 | Post-treatment |
| SA331667 | V1-19 | Post-treatment |
| SA331668 | V1-16 | Post-treatment |
| SA331669 | V1-17 | Post-treatment |
| SA331670 | V1-18 | Post-treatment |
| SA331671 | V1-2 | Post-treatment |
| SA331672 | V1-1 | Post-treatment |
| SA331673 | V0-9 | Pre-treatment |
| SA331674 | V0-10 | Pre-treatment |
| SA331675 | V0-11 | Pre-treatment |
| SA331676 | V0-12 | Pre-treatment |
| SA331677 | V0-8 | Pre-treatment |
| SA331678 | V0-7 | Pre-treatment |
| SA331679 | V0-2 | Pre-treatment |
| SA331680 | V0-3 | Pre-treatment |
| SA331681 | V0-4 | Pre-treatment |
| SA331682 | V0-6 | Pre-treatment |
| SA331683 | V0-13 | Pre-treatment |
| SA331684 | V0-14 | Pre-treatment |
| SA331685 | V0-21 | Pre-treatment |
| SA331686 | V0-22 | Pre-treatment |
| SA331687 | V0-25 | Pre-treatment |
| SA331688 | V0-28 | Pre-treatment |
| SA331689 | V0-20 | Pre-treatment |
| SA331690 | V0-19 | Pre-treatment |
| SA331691 | V0-15 | Pre-treatment |
| SA331692 | V0-16 | Pre-treatment |
| SA331693 | V0-17 | Pre-treatment |
| SA331694 | V0-18 | Pre-treatment |
| SA331695 | V0-1 | Pre-treatment |
| Showing results 1 to 46 of 46 |
Collection:
| Collection ID: | CO003164 |
| Collection Summary: | The study was approved by the Institutional Review Board of the College of Medicine, King Saud University, Riyadh, Saudi Arabia (registration no. E-18-3075). Recruited patients were asked to sign a written informed consent form before enrolling. Twenty patients who were diagnosed with T2DM were referred to the King Khaled University Hospital's (KKUH), Obesity Research Center, where this study took place. Patients were treated with an appropriate dose of Liraglutide for a three months as described previously (8). Samples were taken pre-treatment and post-treatment. Note: the T2DM participants were on other medications including insulin and metformin beside the Liraglutide treatment. |
| Collection Protocol ID: | Liraglutide_sample_collection.pdf |
| Collection Protocol Filename: | Liraglutide_sample_collection.pdf |
| Sample Type: | Blood (plasma) |
Treatment:
| Treatment ID: | TR003180 |
| Treatment Summary: | Patients with indications of add-on liraglutide were started on treatment by their physician in a scaled-up dose from 0.6 mg to 1.8 mg of a once-daily subcutaneous injection over a period of three weeks. The follow-up visit was scheduled 3 months after receiving the full dose (1.8 mg) of liraglutide. Urine samples were collected at two time points: one sample before and another sample after treatment with liraglutide. Blood samples were collected by venipuncture into plain tubes (Vacutainer, BD Biosciences, San Jose, CA, USA) from each patient after a 10 h fast. The plasma was separated by centrifugation (15 min, 3000× g), divided into several aliquots, and stored at −80 °C for further analysis. |
| Treatment Compound: | Liraglutide |
Sample Preparation:
| Sampleprep ID: | SP003177 |
| Sampleprep Summary: | Metabolite extraction was performed as mentioned elsewhere [1]. Briefly,100 μL aliquot of plasma was mixed with 900 μL of an extraction solvent 1:1 acetonitrile (ACN): methanol (MeOH). Concurrently, quality control (QC) samples were generated by taking aliquots from all samples to verify system stability. The mixtures were agitated on a thermomixer (Eppendorf, CITY, Germany) at 600 rpm and kept at room temperature (RT) for one hour. Subsequently, the samples underwent centrifugation at 16000 rpm, at a temperature of 4ºC, for a duration of 10 minutes. After centrifugation, 950 μL of the resultant supernatant was transferred into a 1.5-ml Eppendorf tube and then subjected to complete evaporation using a SpeedVac system (Christ, Germany). The dried samples were reconstituted with 100 μL of a 50% mobile phase A and B (A: 0.1% Formic acid in dH2O, B: 0.1% Formic acid in 50% ACN: MeOH). This reconstitution was followed by brief vortexing and then introduced into the LC-MS system for analysis. |
| Sampleprep Protocol Filename: | Saxenda_Metabolite_Extraction.pdf |
Combined analysis:
| Analysis ID | AN005010 | AN005011 |
|---|---|---|
| Analysis type | MS | MS |
| Chromatography type | Reversed phase | Reversed phase |
| Chromatography system | Waters Acquity UPLC | Waters Acquity UPLC |
| Column | Waters XSelect HSS C18 (100 × 2.1mm,2.5um) | Waters XSelect HSS C18 (100 × 2.1mm,2.5um) |
| MS Type | ESI | ESI |
| MS instrument type | QTOF | QTOF |
| MS instrument name | Waters Xevo-G2-S | Waters Xevo-G2-S |
| Ion Mode | POSITIVE | NEGATIVE |
| Units | Area | Area |
Chromatography:
| Chromatography ID: | CH003784 |
| Chromatography Summary: | Waters Acquity UPLC system coupled with a Xevo G2-S QTOF mass spectrometer with an electrospray ionization source (ESI) was used to explore the metabolic profile. The extracted metabolites were separated using an ACQUITY UPLC using an XSelect column (100×2.1mm 2.5 μm) (Waters Ltd., Elstree, UK). Mobile phase solvent A was 0.1% formic acid in dH2O, while solvent B consisted of 0.1% formic acid in 50% ACN: MeOH. A gradient elution program was run: 0-16 min with 95-5% A, 16-19 min at 5% A, 19-20 min 5-95% A, and 20-22 min maintaining 5-95% A, all at a flow rate of 300 µL/min. MS spectra were obtained in both positive (ESI+) and negative (ESI-) electrospray ionization modes. The MS parameters were as follows: source temperature at 150°C, desolvation temperature at 500°C (ESI+) or 140°C (ESI-), capillary voltage at 3.20 kV (ESI+) or 3 kV (ESI-), cone voltage at 40 V, desolvation gas flow at 800.0 L/h, and cone gas flow at 50 L/h. Collision energies for low and high functions were set at off and 10 V to 50 V, respectively, in MSE mode. The mass spectrometer was calibrated using sodium formate in the 100–1200 Da range. Data were collected using Masslynx™ V4.1 workstation in continuum mode (Waters Inc., Milford, Massachusetts, USA). |
| Methods Filename: | Saxenda_LC_MS.pdf |
| Instrument Name: | Waters Acquity UPLC |
| Column Name: | Waters XSelect HSS C18 (100 × 2.1mm,2.5um) |
| Column Temperature: | 55 |
| Flow Gradient: | 0-16 min 95- 5% A, 16-19 min 5% A, 19-20 min 5-95% A, 20-22 min 95- 95% A |
| Flow Rate: | 300 µL/min |
| Solvent A: | 100% water; 0.1% formic acid |
| Solvent B: | 50% methanol/50% acetonitrile; 0.1% formic acid |
| Chromatography Type: | Reversed phase |
MS:
| MS ID: | MS004749 |
| Analysis ID: | AN005010 |
| Instrument Name: | Waters Xevo-G2-S |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | The DIA data were collected with a Masslynx™ V4.1 workstation in continuum mode (Waters Inc., Milford, MA, USA). The raw MS data were processed following a standard pipeline using the Progenesis QI v.3.0 software. |
| Ion Mode: | POSITIVE |
| Analysis Protocol File: | Saxenda_LC_MS.pdf |
| MS ID: | MS004750 |
| Analysis ID: | AN005011 |
| Instrument Name: | Waters Xevo-G2-S |
| Instrument Type: | QTOF |
| MS Type: | ESI |
| MS Comments: | The DIA data were collected with a Masslynx™ V4.1 workstation in continuum mode (Waters Inc., Milford, MA, USA). The raw MS data were processed following a standard pipeline using the Progenesis QI v.3.0 software. |
| Ion Mode: | NEGATIVE |
| Analysis Protocol File: | Saxenda_LC_MS.pdf |
