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Metabolite Profiling in a Diet-Induced Obesity Mouse Model and Individuals with Diabetes: A Combined Mass Spectrometry and Proton Nuclear Magnetic Resonance Spectroscopy Study

Vieira, João LU ; Ottosson, Filip LU ; Jujic, Amra LU ; Denisov, Vladimir LU ; Magnusson, Martin LU orcid ; Melander, Olle LU orcid and Duarte, Joao LU orcid (2023) In Metabolites 13(7).
Abstract
Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy techniques have been used extensively for metabolite profiling. Although combining these two analytical modalities has the potential of enhancing metabolite coverage, such studies are sparse. In this study we test the hypothesis that combining the metabolic information obtained using liquid chromatography (LC) MS and 1H NMR spectroscopy improves the discrimination of metabolic disease development. We induced metabolic syndrome in male mice using a high-fat diet (HFD) exposure and performed LC-MS and NMR spectroscopy on plasma samples collected after 1 and 8 weeks of dietary intervention. In an orthogonal projection to latent structures (OPLS) analysis, we observed... (More)
Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy techniques have been used extensively for metabolite profiling. Although combining these two analytical modalities has the potential of enhancing metabolite coverage, such studies are sparse. In this study we test the hypothesis that combining the metabolic information obtained using liquid chromatography (LC) MS and 1H NMR spectroscopy improves the discrimination of metabolic disease development. We induced metabolic syndrome in male mice using a high-fat diet (HFD) exposure and performed LC-MS and NMR spectroscopy on plasma samples collected after 1 and 8 weeks of dietary intervention. In an orthogonal projection to latent structures (OPLS) analysis, we observed that combining MS and NMR was stronger than each analytical method alone at determining effects of both HFD feeding and time-on-diet. We then tested our metabolomics approach on plasma from 56 individuals from the Malmö Diet and Cancer Study (MDCS) cohort. All metabolic pathways impacted by HFD feeding in mice were confirmed to be affected by diabetes in the MDCS cohort, and most prominent HFD-induced metabolite concentration changes in mice were also associated with metabolic syndrome parameters in humans. The main drivers of metabolic disease discrimination emanating from the present study included plasma levels of xanthine, hippurate, 2-hydroxyisovalerate, S-adenosylhomocysteine and dimethylguanidino valeric acid. In conclusion, our combined NMR-MS approach provided a snapshot of metabolic imbalances in humans and a mouse model, which was improved over employment of each analytical method alone. (Less)
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author
; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
metabolomics, LC-MS, NMR, plasma, biomarkers
in
Metabolites
volume
13
issue
7
article number
874
publisher
MDPI AG
external identifiers
  • scopus:85166284794
  • pmid:37512581
ISSN
2218-1989
DOI
10.3390/metabo13070874
language
English
LU publication?
yes
id
19a08f3a-671b-42a7-bbef-8a45a14ed242
date added to LUP
2023-07-26 16:05:25
date last changed
2024-01-19 01:14:19
@article{19a08f3a-671b-42a7-bbef-8a45a14ed242,
  abstract     = {{Mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopy techniques have been used extensively for metabolite profiling. Although combining these two analytical modalities has the potential of enhancing metabolite coverage, such studies are sparse. In this study we test the hypothesis that combining the metabolic information obtained using liquid chromatography (LC) MS and 1H NMR spectroscopy improves the discrimination of metabolic disease development. We induced metabolic syndrome in male mice using a high-fat diet (HFD) exposure and performed LC-MS and NMR spectroscopy on plasma samples collected after 1 and 8 weeks of dietary intervention. In an orthogonal projection to latent structures (OPLS) analysis, we observed that combining MS and NMR was stronger than each analytical method alone at determining effects of both HFD feeding and time-on-diet. We then tested our metabolomics approach on plasma from 56 individuals from the Malmö Diet and Cancer Study (MDCS) cohort. All metabolic pathways impacted by HFD feeding in mice were confirmed to be affected by diabetes in the MDCS cohort, and most prominent HFD-induced metabolite concentration changes in mice were also associated with metabolic syndrome parameters in humans. The main drivers of metabolic disease discrimination emanating from the present study included plasma levels of xanthine, hippurate, 2-hydroxyisovalerate, S-adenosylhomocysteine and dimethylguanidino valeric acid. In conclusion, our combined NMR-MS approach provided a snapshot of metabolic imbalances in humans and a mouse model, which was improved over employment of each analytical method alone.}},
  author       = {{Vieira, João and Ottosson, Filip and Jujic, Amra and Denisov, Vladimir and Magnusson, Martin and Melander, Olle and Duarte, Joao}},
  issn         = {{2218-1989}},
  keywords     = {{metabolomics; LC-MS; NMR; plasma; biomarkers}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  publisher    = {{MDPI AG}},
  series       = {{Metabolites}},
  title        = {{Metabolite Profiling in a Diet-Induced Obesity Mouse Model and Individuals with Diabetes: A Combined Mass Spectrometry and Proton Nuclear Magnetic Resonance Spectroscopy Study}},
  url          = {{http://dx.doi.org/10.3390/metabo13070874}},
  doi          = {{10.3390/metabo13070874}},
  volume       = {{13}},
  year         = {{2023}},
}