Metabolomics Data Deposition from Cardiac metabolomic profile of the naked mole-rat—glycogen to the rescue

The African naked mole-rat (Heterocephalus glaber) is unique among mammals, displaying extreme longevity, resistance to cardiovascular disease and an ability to survive long periods of extreme hypoxia. The metabolic adaptations required for resistance to hypoxia are hotly debated and a recent report provides evidence that they are able to switch from glucose to fructose driven glycolysis in the brain. However, other systemic alterations in their metabolism are largely unknown. In the current study, a semi-targeted high resolution 1H magnetic resonance spectroscopy (MRS) metabolomics investigation was performed on cardiac tissue from the naked mole-rat (NMR) and wild-type C57/BL6 mice to better understand these adaptations. A range of metabolic differences was observed in the NMR including increased lactate, consistent with enhanced rates of glycolysis previously reported, increased glutathione, suggesting increased resistance to oxidative stress and decreased succinate/fumarate ratio suggesting reduced oxidative phosphorylation and ROS production. Surprisingly, the most significant difference was an elevation of glycogen stores and glucose-1-phosphate resulting from glycogen turnover, that were completely absent in the mouse heart and above the levels found in the mouse liver. Thus, we identified a range of metabolic adaptations in the NMR heart that are relevant to their ability to survive extreme environmental pressures and metabolic stress. Our study underscores the plasticity of energetic pathways and the need for compensatory strategies to adapt in response to the physiological and pathological stress including ageing and ischaemic heart pathologies.非洲裸鼹鼠（Heterocephalus glaber）是哺乳动物中独具特色的物种，兼具极端长寿、抗心血管疾病能力，以及可在长期极端缺氧环境下存活的特性。其抗缺氧所需的代谢适应机制一直是学界热议的话题，近期有研究证实，裸鼹鼠的大脑可从以葡萄糖驱动的糖酵解切换为以果糖驱动的糖酵解。但目前学界对其代谢层面的其他系统性改变仍知之甚少。在本研究中，研究人员针对裸鼹鼠（NMR）与野生型C57/BL6小鼠的心脏组织，开展了半靶向高分辨率1H磁共振波谱（MRS）代谢组学分析，以深入解析这类代谢适应机制。研究观察到裸鼹鼠存在一系列代谢差异：包括与此前报道的糖酵解速率提升相符的乳酸水平升高；谷胱甘肽含量上升，提示其抗氧化应激能力增强；琥珀酸/延胡索酸比值降低，表明氧化磷酸化活性与活性氧（ROS）生成量均有所下降。令人意外的是，最显著的差异在于糖原储备与糖原代谢产生的葡萄糖-1-磷酸水平显著升高——这类物质在小鼠心脏中完全缺失，且含量远超小鼠肝脏中的水平。综上，本研究鉴定出裸鼹鼠心脏中的一系列代谢适应特征，这些特征与其耐受极端环境压力与代谢应激的能力密切相关。本研究凸显了能量代谢通路的可塑性，同时也强调了针对包括衰老与缺血性心脏病在内的生理及病理应激制定适应性补偿策略的必要性。