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Cold exposure induces transcriptomic and metabolic reprogramming in the heart: An integrated multiomics study
Jiaming Ju, Zhengchao Wen, Jiayun Li, Dandan Zhang, Kejiao Zhang, Haozhan Wang, Roman E. Tokmachev, Yang Li, Yanan Jiang
2026, 6(2): 97-108. doi: 10.1515/fzm-2026-0010
Keywords: cold exposure, RNA sequencing, cardiometabolic
  Objective  Exposure to extreme cold temperatures may increase the risk of cardiovascular diseases. This study aimed to investigate the effects of cold exposure on the heart and its underlying mechanisms using an integrated transcriptomic and metabolomic approach.  Methods  C57BL/6 mice were subjected to cold exposure at 4 ℃ for 12 hours per day for 4 weeks. Transcriptomics and metabolomics profiles of the heart were analyzed. Differentially expressed genes (DEGs) and differentially expressed metabolites (DEMs) were identified, and mRNA expression levels were validated by qRT-PCR. Enrichment analyses were performed to identify significantly affected pathways. Transcriptomic and metabolomic data were then integrated to provide a comprehensive view of molecular alterations induced by cold exposure. To further evaluate the relationship between cold exposure and cardiovascular diseases, a myocardial infarction (MI) mouse model was established, and overlapping genes between cold exposure and MI were analyzed.  Results  Cold exposure significantly altered both the transcriptomic and metabolomic profiles of mouse hearts. Pathway enrichment analyses based on DEGs and DEMs identified several signaling pathways affected by cold stress. Integrated transcriptomic and metabolomic analyses further highlighted potential metabolic and signaling pathways associated with cold exposure. By cross-referencing DEGs associated with cold exposure with those from the MI model in the GEO database (GSE223208), 34 overlapping genes were identified. Integrated analyses implicated key genes (Tnfrsf12a and Nppb) in cold-aggravated cardiac remodeling, which were further validated in MI models.  Conclusion  Cold exposure reprograms the cardiac transcriptome and metabolome in mice. Cold exposure and MI share a subset of DEGs, which may help illuminate the pathophysiological interplay between cold stress and MI, highlighting potential therapeutic targets for cold-exacerbated cardiovascular diseases.
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.