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However, the molecular regulatory mechanisms that underlie this adaptive response are not yet fully understood. This study investigates morphological, functional, genetic, and metabolic changes that occur in the heart of ground squirrels in three groups: summer active (SA),\u00a0late torpor (LT),\u00a0and interbout arousal (IBA).\u00a0Morphological and functional changes in the heart were measured using hematoxylin\u2010eosin (HE)\u00a0staining, Masson staining, echocardiography, and enzyme\u2010linked immunosorbent assay (ELISA).\u00a0Results showed significant changes in cardiac function in the LT group as compared with SA or IBA groups, but no irreversible damage occurred. To understand the molecular mechanisms underlying these phenotypic changes, transcriptomic and metabolomic analyses were conducted to assess differential changes in gene expression and metabolite levels in the three groups of ground squirrels, with a focus on GO\u00a0and KEGG pathway analysis. Transcriptomic analysis showed that differentially expressed genes were involved in the remodeling of cytoskeletal proteins, reduction in protein synthesis, and downregulation of the ubiquitin\u2010proteasome pathway during hibernation (including LT and IBA groups), as compared with the SA group. Metabolomic analysis revealed increased free amino acids, activation of the glutathione antioxidant system, altered cardiac fatty acid metabolic preferences, and enhanced pentose phosphate pathway activity during hibernation as compared with the SA group. Combining the transcriptomic and metabolomic data, active mitochondrial oxidative phosphorylation and creatine\u2010phosphocreatine energy shuttle systems were observed, as well as inhibition of ferroptosis signaling pathways during hibernation as compared with the SA group. In conclusion, these results provide new insights into cardio\u2010protection in hibernators from the perspective of gene and metabolite changes and deepen our understanding of adaptive cardio\u2010protection mechanisms in mammalian hibernators.<\/jats:p>","DOI":"10.1002\/jcp.31123","type":"journal-article","created":{"date-parts":[[2023,9,21]],"date-time":"2023-09-21T16:58:50Z","timestamp":1695315530000},"page":"2724-2748","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Integrated transcriptomics and metabolomics reveal protective effects on heart of hibernating Daurian ground squirrels"],"prefix":"10.1002","volume":"238","author":[{"given":"Yingyu","family":"Yang","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory for Animal Conservation, College of Life Sciences Northwest University Xi'an 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