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Discrimination of steatosis and NASH in mice using nuclear magnetic resonance spectroscopy

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Abstract

Nonalcoholic fatty liver disease (NAFLD) is a common cause of hepatic dysfunction. The disease spectrum ranges from hepatic steatosis to nonalcoholic steatohepatitis (NASH). The aim of this study was to identify metabolic differences in murine models of simple hepatic steatosis and NASH for the distinction of these NAFLD stages. For 12 weeks, male BALB/c mice were fed either a control or two different high-fat diets leading to hepatic steatosis and NASH, respectively. Metabolic differences were determined by independent component analysis (ICA) of nuclear magnetic resonance (NMR) spectra of lipophilic and hydrophilic liver extracts, and urine specimens. The results from ICA clearly discriminated the three investigated groups. Discriminatory biomarkers in the lipophilic liver extracts were free cholesterol, cholesterol ester and lipid methylene. Discrimination of the hydrophilic liver extracts was mainly mediated by betaine, glucose, and lactate, whereas in urine taurine, trimethylamine-N-oxide, and trimethylamine were the most discriminatory biomarkers. In conclusion, NMR metabolite fingerprinting of spot urine specimens may allow the noninvasive distinction of steatosis and NASH.

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Acknowledgments

The authors thank Ann-Kathrin Immervoll for assistance in sample preparation and Daniela Herold for statistical advice.

Funding

This study was funded by BayGene and the Regensburg ReForM program. The authors who have taken part in this study declared that they do not have anything to disclose regarding funding from industry or conflict of interest with respect to this manuscript.

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Authors and Affiliations

  1. Institute of Functional Genomics, University of Regensburg, Josef-Engert-Strasse 9, 93053, Regensburg, Germany

    Matthias S. Klein, Peter J. Oefner & Wolfram Gronwald

  2. Department of Internal Medicine I, University Clinic of Regensburg, 93042, Regensburg, Germany

    Christoph Dorn, Michael Saugspier & Claus Hellerbrand

Authors
  1. Matthias S. Klein
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  2. Christoph Dorn
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  3. Michael Saugspier
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  4. Claus Hellerbrand
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  5. Peter J. Oefner
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  6. Wolfram Gronwald
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Correspondence to Wolfram Gronwald.

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Klein, M.S., Dorn, C., Saugspier, M. et al. Discrimination of steatosis and NASH in mice using nuclear magnetic resonance spectroscopy. Metabolomics 7, 237–246 (2011). https://doi.org/10.1007/s11306-010-0243-6

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  • DOI: https://doi.org/10.1007/s11306-010-0243-6

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