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A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation

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Abstract

Introduction

Hypothermia is a potentially lethal condition whose postmortem diagnosis is often complex to perform due to the absence of pathognomonic lesions and biomarkers. Our first study of human serum and urinary metabolome in hypothermia fatalities sought novel biomarkers with better diagnostic performances than those already existing.

Material and Method

Thirty-two cases of hypothermia deaths and 16 cases excluding known antemortem exposure to cold or postmortem elements suggesting hypothermia were selected. A targeted metabolomic study allowing the detection and quantitation of 188 metabolites was performed on collected serum and urine using direct flow injection (FIA) and liquid chromatography (LC) separation, both coupled to tandem mass spectrometry (MS/MS). Amino acid quantification was also carried on using an in-house LC-MS/MS method in order to replicate the results obtained with the metabolomic study.

Results

A discriminant metabolic signature allowing a clear separation between hypothermia and control groups was obtained in the serum. This signature was characterized by increased arginase activity and fatty acid unsaturation along with decreased levels of tryptophan in hypothermia fatalities compared to controls. By contrast, no discriminant metabolic signature separating hypothermia from control fatalities was found in urines.

Discussion

The serum metabolic signature of hypothermia fatalities herein observed pointed toward metabolic adaptations that likely aimed at heat production enhancement, endothelial function, and cell membrane fluidity preservation. Novel biomarkers potentially useful in a hypothermia diagnosis were also identified.

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Acknowledgements

We would like to thank Lydie Tessier and Cédric Gadras for technical support and Donnalee Perez for language editing.

Author information

Authors and Affiliations

  1. Service de médecine légale et pénitentiaire, Centre Hospitalier Universitaire d’Angers, 49933, Angers Cedex 09, France

    Guillaume Rousseau & Nathalie Jousset

  2. Département de biochimie et génétique, Centre Hospitalier Universitaire d’Angers, 49933, Angers Cedex 09, France

    Guillaume Rousseau, Juan Manuel Chao de la Barca, Xavier Dieu, Floris Chabrun, Delphine Prunier-Mirabeau, Gilles Simard & Pascal Reynier

  3. Unité Mixte de Recherche MITOVASC, Equipe Mitolab, CNRS 6015, INSERM 1083, Université d’Angers, 49035, Angers Cedex 01, France

    Guillaume Rousseau, Juan Manuel Chao de la Barca, Xavier Dieu, Floris Chabrun, Delphine Prunier-Mirabeau & Pascal Reynier

  4. GEROM-LHEA, IRIS-IBS Institut de Biologie en Santé, Centre Hospitalier Universitaire d’Angers, 49933, Angers Cedex 09, France

    Clotilde Rougé-Maillart

  5. Department of Forensic Medicine, Medical University of Lublin, Lublin, Poland

    Grzegorz Teresiński

  6. Centre Universitaire Romand de Médecine Légale, Hôpital Universitaire de Lausanne, Chemin de la Vuliette 4, 1000, Lausanne 25, Switzerland

    Cristian Palmiere

Authors
  1. Guillaume Rousseau
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  2. Juan Manuel Chao de la Barca
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  10. Pascal Reynier
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  11. Cristian Palmiere
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Corresponding author

Correspondence to Guillaume Rousseau.

Ethics declarations

We confirm that all cases selected for this work underwent medicolegal autopsies directed by the public prosecutor. Biochemical investigations were performed as part of investigations.

Conflict of interest

The authors declare that they have no conflict of interest.

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Results of the serum metabolomics study. (XLSX 84.1 kb)

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Results of the urine metabolomics study (XLSX 62.2 kb)

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Rousseau, G., Chao de la Barca, J.M., Rougé-Maillart, C. et al. A serum metabolomics signature of hypothermia fatalities involving arginase activity, tryptophan content, and phosphatidylcholine saturation. Int J Legal Med 133, 889–898 (2019). https://doi.org/10.1007/s00414-018-1937-y

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  • DOI: https://doi.org/10.1007/s00414-018-1937-y

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