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Metabolites
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New Advances in Tissue Metabolomics
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New Advances in Tissue Metabolomics

A special issue of Metabolites (ISSN 2218-1989). This special issue belongs to the section "Integrative Metabolomics".

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 19912

Special Issue Editor

Prof. Dr. Philip Britz-McKibbin

E-Mail Website
Guest Editor
Department of Chemistry and Chemical Biology, McMaster University, Hamilton, ON L8S 4M1, Canada
Interests: metabolomics; CE-MS; method development; clinical biomarkers; population health; nutrition

Special Issue Information

Dear Colleagues,

Metabolomics offers an exciting approach toward understanding the underlying mechanisms of human diseases based on comprehensive profiling of metabolites and/or lipids in complex biological samples. To date, most studies have focused on the analysis of more accessible biofluids (e.g., urine, blood) in clinical metabolomic studies using high resolution mass spectrometry and NMR methods. However, tissue-based metabolomic studies offer unique insights into localized intracellular changes in metabolic phenotypes as a function of external stressors that are often obscured by conventional analyses of biofluids. In this Special Issue, researchers are encouraged to submit manuscripts concerning targeted and nontargeted methods for metabolite and/or lipid profiling of specific tissue specimens (e.g., muscle, adipose, liver, placenta, etc.) from human participants or animal models. In particular, innovative studies related to new advances in tissue metabolomic studies that address major pre-analytical (e.g., tissue collection, sample preparation, stability studies), analytical (e.g., direct imaging, tissue extract analysis, method development), and post-analytical (e.g., bioinformatics, unknown identification, databases) challenges in the field are especially welcome. 

Dr. Philip Britz-McKibbin
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

  • metabolomics
  • lipidomics
  • tissue
  • mass spectrometry
  • mass spectrometry imaging
  • NMR
  • method development
  • human diseases
  • animal models
  • mechanisms

Published Papers (6 papers)

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Research

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14 pages, 1876 KiB  
Article
Regional Brain Analysis of Modified Amino Acids and Dipeptides during the Sleep/Wake Cycle
by Theodosia Vallianatou, Nicholas B. Bèchet, Mario S. P. Correia, Iben Lundgaard and Daniel Globisch
Metabolites 2022, 12(1), 21; https://doi.org/10.3390/metabo12010021 - 27 Dec 2021
Cited by 6 | Viewed by 3540
Abstract
Sleep is a state in which important restorative and anabolic processes occur. Understanding changes of these metabolic processes during the circadian rhythm in the brain is crucial to elucidate neurophysiological mechanisms important for sleep function. Investigation of amino acid modifications and dipeptides has [...] Read more.
Sleep is a state in which important restorative and anabolic processes occur. Understanding changes of these metabolic processes during the circadian rhythm in the brain is crucial to elucidate neurophysiological mechanisms important for sleep function. Investigation of amino acid modifications and dipeptides has recently emerged as a valuable approach in the metabolic profiling of the central nervous system. Nonetheless, very little is known about the effects of sleep on the brain levels of amino acid analogues. In the present study, we examined brain regional sleep-induced alterations selective for modified amino acids and dipeptides using Ultra-high performance liquid chromatography-MS/MS (UHPLC-MS/MS) based metabolomics. Our approach enabled the detection and identification of numerous amino acid-containing metabolites in the cortex, the hippocampus, the midbrain, and the cerebellum. In particular, analogues of the aromatic amino acids phenylalanine, tyrosine and tryptophan were significantly altered during sleep in the investigated brain regions. Cortical levels of medium and long chain N-acyl glycines were higher during sleep. Regional specific changes were also detected, especially related to tyrosine analogues in the hippocampus and the cerebellum. Our findings demonstrate a strong correlation between circadian rhythms and amino acid metabolism specific for different brain regions that provide previously unknown insights in brain metabolism. Full article
(This article belongs to the Special Issue New Advances in Tissue Metabolomics)
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12 pages, 3701 KiB  
Article
Lipidomic Analysis of Archival Pathology Specimens Identifies Altered Lipid Signatures in Ovarian Clear Cell Carcinoma
by Sartaj Ahmad Mir, Soon Boon Justin Wong, Kothandaraman Narasimhan, Chua W. L. Esther, Shanshan Ji, Bo Burla, Markus R. Wenk, David S. P. Tan and Anne K. Bendt
Metabolites 2021, 11(9), 597; https://doi.org/10.3390/metabo11090597 - 03 Sep 2021
Cited by 4 | Viewed by 2347
Abstract
Cancer metabolism is associated with the enhanced lipogenesis required for rapid growth and proliferation. However, the magnitude of dysregulation of diverse lipid species still requires significant characterization, particularly in ovarian clear cell carcinoma (OCCC). Here, we have implemented a robust sample preparation workflow [...] Read more.
Cancer metabolism is associated with the enhanced lipogenesis required for rapid growth and proliferation. However, the magnitude of dysregulation of diverse lipid species still requires significant characterization, particularly in ovarian clear cell carcinoma (OCCC). Here, we have implemented a robust sample preparation workflow together with targeted LC-MS/MS to identify the lipidomic changes in formalin-fixed paraffin-embedded specimens from OCCC compared to tumor-free ovarian tissue. We quantitated 340 lipid species, representing 28 lipid classes. We observed differential regulation of diverse lipid species belonging to several glycerophospholipid classes and trihexosylceramide. A number of unsaturated lipid species were increased in OCCC, whereas saturated lipid species showed a decrease in OCCC compared to the controls. We also carried out total fatty acid analysis and observed an increase in the levels of several unsaturated fatty acids with a concomitant increase in the index of stearoyl-CoA desaturase (SCD) in OCCC. We confirmed the upregulation of SCD (the rate-limiting enzyme for the synthesis of monounsaturated fatty acids) by immunohistochemistry (IHC) assays. Hence, by carrying out a mass spectrometry analysis of archival tissue samples, we were able to provide insights into lipidomic alterations in OCCC. Full article
(This article belongs to the Special Issue New Advances in Tissue Metabolomics)
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16 pages, 3420 KiB  
Article
A Robust Method for Sample Preparation of Gastrointestinal Stromal Tumour for LC/MS Untargeted Metabolomics
by Szymon Macioszek, Danuta Dudzik, Julia Jacyna, Agnieszka Wozniak, Patrick Schöffski and Michał J. Markuszewski
Metabolites 2021, 11(8), 554; https://doi.org/10.3390/metabo11080554 - 21 Aug 2021
Cited by 3 | Viewed by 2966
Abstract
Gastrointestinal stromal tumour has already been well explored at the genome level; however, little is known about metabolic processes occurring in the sarcoma. Sample preparation is a crucial step in untargeted metabolomics workflow, highly affecting the metabolome coverage and the quality of the [...] Read more.
Gastrointestinal stromal tumour has already been well explored at the genome level; however, little is known about metabolic processes occurring in the sarcoma. Sample preparation is a crucial step in untargeted metabolomics workflow, highly affecting the metabolome coverage and the quality of the results. In this study, four liquid-liquid extraction methods for the isolation of endogenous compounds from gastrointestinal stromal tumours were compared and evaluated. The protocols covered two-step or stepwise extraction with methyl-tert-butyl ether (MTBE) or dichloromethane. The extracts were subjected to LC-MS analysis by the application of reversed-phase and hydrophilic interaction liquid chromatography to enable the separation and detection of both polar and nonpolar analytes. The extraction methods were compared in terms of efficiency (total number of detected metabolites) and reproducibility. The method was based on the stepwise extraction with MTBE, methanol, and water proved to be the most reproducible, and thus, its robustness to fluctuations in experimental conditions was assessed employing Plackett–Burman design and hierarchical modelling. While most studied factors had no effect on the metabolite abundance, the highest coefficient value was observed for the volume of MTBE added during extraction. Herein, we demonstrate the application and the feasibility of the selected protocol for the analysis of gastrointestinal stromal tumour samples. The method selected could be considered as a reference for the best characterization of underlying molecular changes associated with complex tissue extracts of GIST. Full article
(This article belongs to the Special Issue New Advances in Tissue Metabolomics)
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15 pages, 2027 KiB  
Article
Metabolomic Recovery as a Result of Ischemic Preconditioning Was More Pronounced in Hippocampus than in Cortex That Appeared More Sensitive to Metabolomic Blood Components
by Eva Baranovicova, Dagmar Kalenska, Marian Grendar and Jan Lehotsky
Metabolites 2021, 11(8), 516; https://doi.org/10.3390/metabo11080516 - 05 Aug 2021
Cited by 6 | Viewed by 1954
Abstract
The study of an organism’s response to ischemia at different levels is essential to understand the mechanism of the injury as well as protection. We used the occlusion of four vessels as an animal model of global cerebral ischemia to investigate metabolic alterations [...] Read more.
The study of an organism’s response to ischemia at different levels is essential to understand the mechanism of the injury as well as protection. We used the occlusion of four vessels as an animal model of global cerebral ischemia to investigate metabolic alterations in cerebral cortex, hippocampus, blood plasma, as well as in a remote organ, the heart, in rats undergoing 24 h postischemic reperfusion. By inducing sublethal ischemic stimuli, we focused on endogenous phenomena known as ischemic tolerance that is currently the best known and most effective way of protecting against ischemic injury. NMR spectroscopy was used to analyze relative metabolite levels in homogenates from rats’ cerebral cortex, hippocampus, and heart together with deproteinized blood plasma. In individual animals subjected to global cerebral ischemia, relative concentrations of the essential amino acids isoleucine, valine, phenylalanine, and tyrosine in cerebral cortex correlated with those in blood plasma (p < 0.05, or boundary significant p < 0.09). This did not apply for the hippocampus, suggesting a closer relation between ischemic cortex and metabolomic blood components. Hippocampal non-participation on correlation with blood components may emphasize the observed partial or full normalization the post-ischemically altered levels of a number of metabolites in the preconditioned animals. Remarkably, that was observed for cortex to a lesser extent. As a response to the global cerebral ischemia in heart tissue, we observed decreased glutamate and increased 3-hydroxybutyrate. Ischemically induced semi-ketotic state and other changes found in blood plasma partially normalized when ischemic preconditioning was introduced. Some metabolomic changes were so strong that even individual metabolites were able to differentiate between ischemic, ischemically preconditioned, and control brain tissues. Full article
(This article belongs to the Special Issue New Advances in Tissue Metabolomics)
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11 pages, 1170 KiB  
Article
Comprehensive Dipeptide Analysis Revealed Cancer-Specific Profile in the Liver of Patients with Hepatocellular Carcinoma and Hepatitis
by Hitoshi Ozawa, Akiyoshi Hirayama, Futaba Shoji, Midori Maruyama, Kumi Suzuki, Hisami Yamanaka-Okumura, Hiroshi Tatano, Yuji Morine, Tomoyoshi Soga, Mitsuo Shimada and Masaru Tomita
Metabolites 2020, 10(11), 442; https://doi.org/10.3390/metabo10110442 - 01 Nov 2020
Cited by 13 | Viewed by 2554
Abstract
As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, [...] Read more.
As the physical properties and functionality of dipeptides differ from those of amino acids, they have attracted attention in metabolomics; however, their functions in vivo have not been clarified in detail. Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer, and its major cause is chronic hepatitis. This study was conducted to explore tumor-specific dipeptide characteristics by performing comprehensive dipeptide analysis in the tumor and surrounding nontumor tissue of patients with HCC. Dipeptides were analyzed by liquid chromatography tandem mass spectrometry and capillary electrophoresis tandem mass spectrometry. Principal component analysis using 236 detected dipeptides showed differences in the dipeptide profiles between nontumor and tumor tissues; however, no clear difference was observed in etiological comparison. In addition, the N- and C-terminal amino acid compositions of the detected dipeptides significantly differed, suggesting the substrate specificity of enzyme proteins, such as peptidase. Furthermore, hepatitis-derived HCC may show a characteristic dipeptide profile even before tumor formation. These results provide insight into HCC pathogenesis and may help identify novel biomarkers for diagnosis. Full article
(This article belongs to the Special Issue New Advances in Tissue Metabolomics)
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Review

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25 pages, 2754 KiB  
Review
New Advances in Tissue Metabolomics: A Review
by Michelle Saoi and Philip Britz-McKibbin
Metabolites 2021, 11(10), 672; https://doi.org/10.3390/metabo11100672 - 30 Sep 2021
Cited by 38 | Viewed by 5246
Abstract
Metabolomics offers a hypothesis-generating approach for biomarker discovery in clinical medicine while also providing better understanding of the underlying mechanisms of chronic diseases. Clinical metabolomic studies largely rely on human biofluids (e.g., plasma, urine) as a more convenient specimen type for investigation. However, [...] Read more.
Metabolomics offers a hypothesis-generating approach for biomarker discovery in clinical medicine while also providing better understanding of the underlying mechanisms of chronic diseases. Clinical metabolomic studies largely rely on human biofluids (e.g., plasma, urine) as a more convenient specimen type for investigation. However, biofluids are non-organ specific reflecting complex biochemical processes throughout the body, which may complicate biochemical interpretations. For these reasons, tissue metabolomic studies enable deeper insights into aberrant metabolism occurring at the direct site of disease pathogenesis. This review highlights new advances in metabolomics for ex vivo analysis, as well as in situ imaging of tissue specimens, including diverse tissue types from animal models and human participants. Moreover, we discuss key pre-analytical and post-analytical challenges in tissue metabolomics for robust biomarker discovery with a focus on new methodological advances introduced over the past six years, including innovative clinical applications for improved screening, diagnostic testing, and therapeutic interventions for cancer. Full article
(This article belongs to the Special Issue New Advances in Tissue Metabolomics)
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