AUTHOR=Li Jia-Hao , Liu Jia-Li , Song Jian-Wen , Deng Wei-Liang , Cao Xin-Zhi , Wu Zhong-Wen , Chen Ding-Hao , Wang Hui , Yu Song , Wang Qi TITLE=Metabolomic analysis of fatal hypothermia using ultra-high-performance liquid chromatography‒mass spectrometry JOURNAL=Frontiers in Molecular Biosciences VOLUME=Volume 12 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2025.1563642 DOI=10.3389/fmolb.2025.1563642 ISSN=2296-889X ABSTRACT=IntroductionThe identification of fatal hypothermia remains a significant challenge in forensic medicine. Metabolomics, which reflects the overall changes in endogenous metabolites within an organism, holds substantial value in the exploration of disease mechanisms and the screening of molecular markers.MethodsUsing ultra-high-performance liquid chromatography‒mass spectrometry (UHPLC‒MS), we conducted a metabolomic analysis of serum, heart, lung, and kidney tissues from mice with fatal hypothermia.ResultsA total of 67 metabolites significantly differed across all the tissues, involving pathways such as the TCA cycle, fatty acid oxidation, arginine metabolism, histamine metabolism, and antioxidant-related pathways. Each tissue also displayed unique metabolic alterations. Additionally, we observed significant differences in the metabolomic profiles of kidney tissues from mice with different survival times.ConclusionOur findings contribute to elucidate the underlying mechanisms involved and provide a foundation for the forensic identification of markers of fatal hypothermia.