International Journal of Legal Medicine

, Volume 133, Issue 3, pp 889–898 | Cite as

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

  • Guillaume RousseauEmail author
  • Juan Manuel Chao de la Barca
  • Clotilde Rougé-Maillart
  • Grzegorz Teresiński
  • Nathalie Jousset
  • Xavier Dieu
  • Floris Chabrun
  • Delphine Prunier-Mirabeau
  • Gilles Simard
  • Pascal Reynier
  • Cristian Palmiere
Original Article



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.


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.


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.


Forensic science Hypothermia Metabolomics Serum Urine Biomarkers 



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

Compliance with ethical standards

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.

Supplementary material

414_2018_1937_MOESM1_ESM.pdf (200 kb)
Online Resource 1 (PDF 199 kb)
414_2018_1937_MOESM2_ESM.xlsx (84 kb)
Online Resource 2 Results of the serum metabolomics study. (XLSX 84.1 kb)
414_2018_1937_MOESM3_ESM.xlsx (62 kb)
Online Resource 3 Results of the urine metabolomics study (XLSX 62.2 kb)


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  • Guillaume Rousseau
    • 1
    • 2
    • 3
    Email author
  • Juan Manuel Chao de la Barca
    • 2
    • 3
  • Clotilde Rougé-Maillart
    • 4
  • Grzegorz Teresiński
    • 5
  • Nathalie Jousset
    • 1
  • Xavier Dieu
    • 2
    • 3
  • Floris Chabrun
    • 2
    • 3
  • Delphine Prunier-Mirabeau
    • 2
    • 3
  • Gilles Simard
    • 2
  • Pascal Reynier
    • 2
    • 3
  • Cristian Palmiere
    • 6
  1. 1.Service de médecine légale et pénitentiaireCentre Hospitalier Universitaire d’AngersAngers Cedex 09France
  2. 2.Département de biochimie et génétiqueCentre Hospitalier Universitaire d’AngersAngers Cedex 09France
  3. 3.Unité Mixte de Recherche MITOVASC, Equipe Mitolab, CNRS 6015, INSERM 1083Université d’AngersAngers Cedex 01France
  4. 4.GEROM-LHEA, IRIS-IBS Institut de Biologie en SantéCentre Hospitalier Universitaire d’AngersAngers Cedex 09France
  5. 5.Department of Forensic MedicineMedical University of LublinLublinPoland
  6. 6.Centre Universitaire Romand de Médecine LégaleHôpital Universitaire de LausanneLausanne 25Switzerland

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