Biomarker patterns and mechanistic insights into hypothermia from a postmortem metabolomics investigation

Linköpings universitet, Avdelningen för klinisk kemi och farmakologi Linköpings universitet, Medicinska fakulteten Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden Karolinska Inst, Sweden; Univ Oulu, Finland RIKEN, Japan Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden Karolinska Inst, Sweden Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden NATURE PORTFOLIO 2024

Postmortem metabolomics holds promise for identifying crucial biological markers relevant to death investigations and clinical scenarios. We aimed to assess its applicability in diagnosing hypothermia, a condition lacking definitive biomarkers. Our retrospective analysis involved 1095 postmortem femoral blood samples, including 150 hypothermia cases, 278 matched controls, and 667 randomly selected test cases, analyzed using UHPLC-QTOF mass spectrometry. The model demonstrated robustness with an R2 and Q2 value of 0.73 and 0.68, achieving 94% classification accuracy, 92% sensitivity, and 96% specificity. Discriminative metabolite patterns, including acylcarnitines, stress hormones, and NAD metabolites, along with identified pathways, suggest that metabolomics analysis can be helpful to diagnose fatal hypothermia. Exposure to cold seems to trigger a stress response in the body, increasing cortisol production to maintain core temperature, possibly explaining the observed upregulation of cortisol levels and alterations in metabolic markers related to renal function. In addition, thermogenesis seems to increase metabolism in brown adipose tissue, contributing to changes in nicotinamide metabolism and elevated levels of ketone bodies and acylcarnitines, these findings highlight the effectiveness of UHPLC-QTOF mass spectrometry, multivariate analysis, and pathway identification of postmortem samples in identifying metabolite markers with forensic and clinical significance. The discovered patterns may offer valuable clinical insights and diagnostic markers, emphasizing the broader potential of postmortem metabolomics in understanding critical states or diseases.
Funding Agencies|Vetenskapsrdet

Postmortem; Metabolomics; Hypothermia; Nicotinamide metabolism; Biomarkers; Biomedical Laboratory Science/Technology; Biomedicinsk laboratorievetenskap/teknologi; Article in journal; info:eu-repo/semantics/article; text

10.1038.s41598-024-68973-9

Open access content. Open access content
info:eu-repo/semantics/restrictedAccess

English

UPE oai:DiVA.org:liu-207165
0000-0002-8015-5728
doi:10.1038/s41598-024-68973-9
PMID 39152132
ISI:001294085700067
1482255132

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