Integrated transcriptomics and metabolomics reveal protective effects on heart of hibernating Daurian ground squirrels

Abstract

Hibernating mammals are natural models of resistance to ischemia, hypoxia‐reperfusion injury, and hypothermia. Daurian ground squirrels (spermophilus dauricus) can adapt to endure multiple torpor‐arousal cycles without sustaining cardiac damage. 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), late torpor (LT), and interbout arousal (IBA). Morphological and functional changes in the heart were measured using hematoxylin‐eosin (HE) staining, Masson staining, echocardiography, and enzyme‐linked immunosorbent assay (ELISA). Results 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 and 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‐proteasome 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‐phosphocreatine 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‐protection in hibernators from the perspective of gene and metabolite changes and deepen our understanding of adaptive cardio‐protection mechanisms in mammalian hibernators.

Yanghe Pingchuan granules mitigates oxidative stress and inflammation in a bronchial asthma rat model: role of the IKK/IκB/NF-κB signalling pathway

“…We used 4% paraformaldehyde to fix tissues (55°C, 1 h). Masson’s trichrome (1%) staining was used to determine the extent of bronchial fibrosis (5–10 min, 55°C) 23 . Then, we evaluated the extent of fibrosis in the lungs and bronchial tissue with an optical microscope and performed pathological grading.…”

Cold resistance of mammalian hibernators ∼ a matter of ferroptosis?

“…Alternatively, the cellular membrane composition of hibernators may be intrinsically distinct from that of non-hibernators, or seasonally adapted to achieve cold resistance and maintain membrane fluidity under cold conditions, which could affect the structure of membrane proteins that are vital for maintaining cellular ion homeostasis ( Aloia and Raison, 1989 ; Giroud et al, 2013 ; Cheff et al, 2021 ). Further efforts to answer these questions in detail will be necessary in specific model hibernators such as Syrian hamsters, in which the causal relationship between genes and phenomena can be functionally addressed, in combination with candidate genes and candidate molecules accumulated through the latest bioinformatics, omics, and comparative approaches in various hibernators, including ground squirrels, marmots, dormice, chipmunks, bats, and bears ( Fedorov et al, 2014 ; Villanueva-Canas et al, 2014 ; Ferris and Gregg, 2019 ; Grabek et al, 2019 ; Jansen et al, 2019 ; Gillen et al, 2021 ; Chen and Mao, 2022 ; Bao et al, 2023 ; Christmas et al, 2023 ; Haugg et al, 2023 ; Heinis et al, 2023 ; Takamatsu et al, 2023 ; Thienel et al, 2023 ; Yang et al, 2023 ). Based on these studies, we will further clarify Q4 and its related question whether cold resistance associated with hibernation originates from a common ancestral trait or as a result of convergent evolution across distinct mammalian clades.…”