Potential Biomarkers of Fatal Hypothermia Revealed by UHPLC-MS Metabolomics in Mice

Background: The postmortem diagnosis of fatal hypothermia presents a considerable challenge in forensic medicine. Metabolomics, a powerful tool reflecting comprehensive changes in endogenous metabolites, offers significant potential for exploring disease mechanisms and identifying diagnostic markers. Methods: In this study, we employed ultra-high-performance liquid chromatography-mass spectrometry (UHPLC-MS) to perform a non-targeted metabolomic analysis of liver, stomach, spleen, and musculus gastrocnemius tissues from mice subjected to fatal hypothermia. Result: A substantial number of differential metabolites were identified in each tissue: 1601 in the liver, 420 in the stomach, 732 in the spleen, and 668 in the gastrocnemius muscle. The most significantly altered metabolites were as follows: magnoflorine (liver, upregulated, ranked first in fold-change), gibberellic acid (stomach, downregulated, ranked first in fold-change), nitrofurantoin (spleen, upregulated, ranked first in fold-change), and isoreserpin (gastrocnemius muscle, downregulated, ranked first in fold-change). Glycerophospholipid metabolism exhibited notable enrichment in all tissues (spleen: second, liver: tenth, stomach: eleventh, gastrocnemius muscle: twenty-first), as did tryptophan metabolism (spleen: thirteenth, liver: eighth, stomach: third, gastrocnemius muscle: seventeenth). Conclusions: Our findings provide insights into the metabolic perturbations associated with fatal hypothermia in different tissues and lay a foundation for the identification of potential tissue biomarkers for forensic diagnosis.