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Metabolites
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Application of Stable Isotope Based Tracer Analysis in Human Cells
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Application of Stable Isotope Based Tracer Analysis in Human Cells

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Metabolomic Profiling Technology".

Deadline for manuscript submissions: closed (31 December 2022) | Viewed by 9615

Special Issue Editor

Prof. Dr. Bart Ghesquiere

E-Mail Website
Guest Editor
Metabolomics Expertise Center, VIB-KU Leuven, 3000 Leuven, Belgium
Interests: mass spectrometry; LC-MS; GC-MS; stable isotope tracing; metabolomics; technologies to understand metabolic rewiring during disease; cancer metabolomics; chromatographic technologies focusing on primary metabolism; bioinformatics tools for metabolite identification and visualization; multiomics

Special Issue Information

Dear Colleagues,

The use of stable isotopes in biomedical research has attracted more and more interest from the metabolomics society. Indeed, the technology of tracer metabolomics has provided unprecedented insights into metabolic pathways playing a critical role in a plethora of disease models. In this Special Issue of Metabolites, we would like to highlight the applicability of stable isotopes (tracer) metabolomics into human metabolism. Topics include but are not limited to molecular insights into disease mechanisms, software tools for tracer metabolomics, metabolic flux analysis, mass-spectrometry-related methodologies for tracer studies, reviews, etc.

Prof. Dr. Bart Ghesquiere
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Metabolites is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • tracer metabolomics
  • stable isotope
  • metabolic flux analysis
  • mass spectrometry
  • human metabolism
  • NMR

Published Papers (4 papers)

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Research

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12 pages, 1908 KiB  
Article
TraVis Pies: A Guide for Stable Isotope Metabolomics Interpretation Using an Intuitive Visualization
by Sam De Craemer, Karen Driesen and Bart Ghesquière
Metabolites 2022, 12(7), 593; https://doi.org/10.3390/metabo12070593 - 25 Jun 2022
Cited by 1 | Viewed by 1978
Abstract
Tracer metabolomics is a powerful technology for the biomedical community to study and understand disease-inflicted metabolic mechanisms. However, the interpretation of tracer metabolomics results is highly technical, as the metabolites’ abundances, tracer incorporation and positions on the metabolic map all must be jointly [...] Read more.
Tracer metabolomics is a powerful technology for the biomedical community to study and understand disease-inflicted metabolic mechanisms. However, the interpretation of tracer metabolomics results is highly technical, as the metabolites’ abundances, tracer incorporation and positions on the metabolic map all must be jointly interpreted. The field is currently lacking a structured approach to help less experienced researchers start the interpretation of tracer metabolomics datasets. We propose an approach using an intuitive visualization concept aided by a novel open-source tool, and provide guidelines on how researchers can apply the approach and the visualization tool to their own datasets. Using a showcase experiment, we demonstrate that the visualization approach leads to an intuitive interpretation that can ease researchers into understanding their tracer metabolomics data. Full article
(This article belongs to the Special Issue Application of Stable Isotope Based Tracer Analysis in Human Cells)
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16 pages, 4312 KiB  
Article
3,3′-Diindolylmethane Enhances Fluorouracil Sensitivity via Inhibition of Pyrimidine Metabolism in Colorectal Cancer
by Jieping Zhang, Shaomin Zou, Yijing Zhang, Ziqing Yang, Wencong Wang, Manqi Meng, Junyan Feng, Peng Zhang, Lishi Xiao, Mong-Hong Lee and Lekun Fang
Metabolites 2022, 12(5), 410; https://doi.org/10.3390/metabo12050410 - 30 Apr 2022
Cited by 5 | Viewed by 1983
Abstract
Chemoresistance limits treatment outcomes in colorectal cancer (CRC) patients. A dimeric metabolite of indole-3-carbinol, 3,3′-diindolylmethane (DIM) is abundant in cruciferous vegetables and has shown anticancer efficacy. The role of DIM in regulating chemosensitivity in CRC remains unknown. In this study, we demonstrated that [...] Read more.
Chemoresistance limits treatment outcomes in colorectal cancer (CRC) patients. A dimeric metabolite of indole-3-carbinol, 3,3′-diindolylmethane (DIM) is abundant in cruciferous vegetables and has shown anticancer efficacy. The role of DIM in regulating chemosensitivity in CRC remains unknown. In this study, we demonstrated that DIM treatment inhibits the malignant progression of CRC. RNA sequencing indicated that pyrimidine synthesis genes are attenuated by DIM treatment. Stable 13C-labeled glucose tracing revealed that DIM inhibits de novo pyrimidine biosynthesis in CRC. DIM increases 5-FU cytotoxicity in CRC via regulation of the expression of pyrimidine metabolism-related genes. DIM synergizes with 5-FU to enhance its inhibitory effects on CRC both in vivo and in vitro. Our results suggest that DIM improves the therapeutic outcomes of FU-based chemotherapy in CRCs by inhibiting pyrimidine metabolism, identifying a new strategy for clinical therapy. Full article
(This article belongs to the Special Issue Application of Stable Isotope Based Tracer Analysis in Human Cells)
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12 pages, 2444 KiB  
Article
Investigations into the In Vitro Metabolism of hGH and IGF-I Employing Stable-Isotope-Labelled Drugs and Monitoring Diagnostic Immonium Ions by High-Resolution/High-Accuracy Mass Spectrometry
by Sophia Krombholz, Andreas Thomas and Mario Thevis
Metabolites 2022, 12(2), 146; https://doi.org/10.3390/metabo12020146 - 04 Feb 2022
Cited by 3 | Viewed by 2177
Abstract
Studying the metabolism of prohibited substances is an essential element in anti-doping research in order to facilitate and improve detectability. Whilst pharmacokinetic studies on healthy volunteers are valuable, they are often difficult, not least due to safety reasons and ethical constraints, especially concerning [...] Read more.
Studying the metabolism of prohibited substances is an essential element in anti-doping research in order to facilitate and improve detectability. Whilst pharmacokinetic studies on healthy volunteers are valuable, they are often difficult, not least due to safety reasons and ethical constraints, especially concerning peptidic substances, which must be administered parenterally. Hence, there is a growing need for suitable in vitro models and sophisticated analytical strategies to investigate the metabolism of protein- and peptide-derived drugs. These include human growth hormone (hGH) and its main mediator insulin-like growth factor-I (IGF-I), both prohibited in professional sports for their anabolic and lipolytic effects, while challenging in their detection, as they occur naturally in the human body.Within this study, the in vitro metabolism of hGH and IGF-I was investigated using a stable-isotope-labelled reporter ion screening strategy (IRIS). A combination of liquid chromatography, high-resolution mass spectrometry, and characteristic immonium ions generated by internal dissociation of the stable-isotope-labelled peptidic metabolites enabled the detection of specific fragments. Several degradation products for hGH and IGF-I were identified within this study. These metabolites, potentially even indicative for subcutaneous administration of the drugs, could serve as promising targets for the detection of hGH and IGF-I misuse in future anti-doping applications. Full article
(This article belongs to the Special Issue Application of Stable Isotope Based Tracer Analysis in Human Cells)
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Review

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19 pages, 1514 KiB  
Review
Understanding Inborn Errors of Metabolism through Metabolomics
by Karen Driesen and Peter Witters
Metabolites 2022, 12(5), 398; https://doi.org/10.3390/metabo12050398 - 27 Apr 2022
Cited by 5 | Viewed by 2527
Abstract
Inborn errors of metabolism (IEMs) are rare diseases caused by a defect in a single enzyme, co-factor, or transport protein. For most IEMs, no effective treatment is available and the exact disease mechanism is unknown. The application of metabolomics and, more specifically, tracer [...] Read more.
Inborn errors of metabolism (IEMs) are rare diseases caused by a defect in a single enzyme, co-factor, or transport protein. For most IEMs, no effective treatment is available and the exact disease mechanism is unknown. The application of metabolomics and, more specifically, tracer metabolomics in IEM research can help to elucidate these disease mechanisms and hence direct novel therapeutic interventions. In this review, we will describe the different approaches to metabolomics in IEM research. We will discuss the strengths and weaknesses of the different sample types that can be used (biofluids, tissues or cells from model organisms; modified cell lines; and patient fibroblasts) and when each of them is appropriate to use. Full article
(This article belongs to the Special Issue Application of Stable Isotope Based Tracer Analysis in Human Cells)
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