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Comprehensive analysis of cold exposure-associated transcriptional and metabolic changes in the liver
Yuzhu Di, Zhengchao Wen, Xiaomin Liu, Kejiao Zhang, Xiuyun Shen, Chunpeng Shi, Yuqiu Chao, Xiao Wang, Shu Wang, Bo Qu, Yanan Jiang
2025, 5(4): 217-230. doi: 10.1515/fzm-2025-0024
Keywords: cold exposure, liver metabolism, transcriptome, metabolome
  Background  Cold exposure is associated with metabolic alterations. This study aims to investigate the effects and mechanisms of cold exposure on liver metabolism through the integration of transcriptomics and metabolomics.  Methods  Liver tissues from mice exposed to cold were subjected to RNA sequencing and liquid chromatography-mass spectrometry (LC-MS) for transcriptomic and metabolomic profiling, respectively. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) were identified. mRNA expression levels were validated by real-time polymerase chain reaction (RT-PCR). Gene ontology (GO), Kyoto encyclopedia of genes and genomes (KEGG), and Reactome enrichment analyses were performed. Finally, transcriptomic and metabolomic data were integrated and analyzed.  Results  Cold exposure altered the transcriptomic and metabolomic profiles in the liver in cold exposed mice. Enrichment analyses were of DEGs and DEMs. Enrichment analyses of DEGs and DEMs revealed that DEGs were involved in pathways such as the PI3K-Akt signaling pathway, cytokine-cytokine receptor interaction, and cell adhesion molecules. DEMs were enriched in pathways related to membrane transport, nucleotide metabolism, and the metabolism of cofactors and vitamins. The integration of transcriptomic and metabolomic data identified several pathways potentially associated with cold exposure, such as the PI3K-Akt signaling pathway.  Conclusion  Cold exposure alters liver transcriptomic and metabolomic profiles in mice. The integrative analysis of transcriptomic and metabolomic data highlights the complexity of the liver's response to cold exposure and identifies potential targets for further investigation.