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

Frigid Zone Medicine ›› 2025, Vol. 5 ›› Issue (4) : 217 -230.

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Frigid Zone Medicine ›› 2025, Vol. 5 ›› Issue (4) :217 -230. DOI: 10.1515/fzm-2025-0024
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Comprehensive analysis of cold exposure-associated transcriptional and metabolic changes in the liver

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Abstract

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.

Keywords

cold exposure / liver metabolism / transcriptome / metabolome

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Yuzhu Di, Zhengchao Wen, Xiaomin Liu, Kejiao Zhang, Xiuyun Shen, Chunpeng Shi, Yuqiu Chao, Xiao Wang, Shu Wang, Bo Qu, Yanan Jiang. Comprehensive analysis of cold exposure-associated transcriptional and metabolic changes in the liver. Frigid Zone Medicine, 2025, 5(4): 217-230 DOI:10.1515/fzm-2025-0024

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Acknowledgement

Not applicable.

Research ethics

All experimental procedures were conducted in full compliance with the Guide for the Care and Use of Laboratory Animals. The study was pre-approved by the Ethics Committee of College of Pharmacy, Harbin Medical University (No. IRB3057723).

Informed consent

Not applicable.

Author contributions

Jiang Y N, Qu B, and Wang S contributed to the conception and design of the study. Di Y Z, Wen Z C, and Zhang K J wrote or contributed to the writing of the manuscript. Shen X Y, Shi C P, and Liu X M performed the biological experiments. Di Y Z, Wen Z C, Chao Y Q, and Wang X conducted the bioinformatics analysis. All authors reviewed and approved the final manuscript.

Use of Large Language Models, AI and Machine Learning Tools

No large language models, AI or machine learning tool was used for any part of the present study.

Conflicts of interest

The authors declare no competing financial interests.

Research funding

This work was supported by the National Natural Science Foundation of China (82370269), the Heilongjiang Postdoctoral Foundation (LBH-Q21134 and LBH-Z22226), and Harbin Medical University Science Foundation (2023).

Data availability

The data that support the findings of this study are available from the corresponding author upon reasonable request.

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