Ojaghi Mohammad, Pamenter Matthew E
Department of Biology, University of Ottawa, Ottawa, ON, Canada, K1N 9A4.
Ottawa Institute of Systems Biology, Ottawa, ON, Canada, K1H 8M5.
J Exp Biol. 2025 Aug 1;228(15). doi: 10.1242/jeb.250397. Epub 2025 Jul 28.
Most vertebrates upregulate anaerobic metabolism in severe hypoxia, which results in metabolic acidosis that must be resolved during reoxygenation. Naked mole-rats (NMRs) are hypoxia-tolerant mammals and drastically reduce their metabolic rate while maintaining systemic pH homeostasis during acute hypoxia. Whether NMRs employ anaerobic metabolism in hypoxia is currently debated. Given the robust systemic hypoxic hypometabolism of this species, we hypothesized that anaerobic metabolism is recruited on a tissue-specific basis that varies between developmental stages and colony caste position. To test this, we treated subordinate juvenile and adult, and breeding (queen) NMRs in normoxia (21% O2) or hypoxia (3% O2) for 1 h, and then measured blood lactate, glycolytic enzyme activity, and the expression of genes that encode for enzymes involved in glycogen and glucose metabolism, and lactate transport. We found that (1) blood lactate levels increase similarly during hypoxia across developmental stages and castes, but that (2) glycolytic activity increased or remained stable in subordinates and juveniles but was unchanged or reduced in queens; (3) MCT4 gene expression decreased markedly in subordinate and juvenile brain and increased in muscle and kidney, but was unchanged in queens; and (4) the expression of genes associated with glycogenolysis and gluconeogenesis varied across tissues in subordinates/juveniles with some markers being down or upregulated or unchanged, but were always unchanged or downregulated queens. Taken together, our results suggest that hypoxia upregulates glycolysis and glycogen mobilization in subordinates and juveniles, but not in queens.
大多数脊椎动物在严重缺氧时会上调无氧代谢，这会导致代谢性酸中毒，而这种酸中毒必须在复氧过程中得到解决。裸鼹鼠是耐缺氧的哺乳动物，在急性缺氧期间，它们会大幅降低代谢率，同时维持全身pH值的稳态。目前关于裸鼹鼠在缺氧时是否利用无氧代谢存在争议。鉴于该物种强大的全身缺氧性低代谢，我们推测无氧代谢是在组织特异性基础上被招募的，且在发育阶段和群体等级地位之间存在差异。为了验证这一点，我们将从属的幼年和成年裸鼹鼠以及繁殖期（王后）裸鼹鼠置于常氧（21% O₂）或缺氧（3% O₂）环境中处理1小时，然后测量血液乳酸、糖酵解酶活性以及编码参与糖原和葡萄糖代谢及乳酸转运的酶的基因表达。我们发现：（1）在缺氧期间，不同发育阶段和等级的裸鼹鼠血液乳酸水平的升高情况相似，但（2）从属裸鼹鼠和幼年裸鼹鼠的糖酵解活性增加或保持稳定，而王后裸鼹鼠的糖酵解活性不变或降低；（3）MCT4基因表达在从属裸鼹鼠和幼年裸鼹鼠的大脑中显著降低，在肌肉和肾脏中增加，而在王后裸鼹鼠中不变；（4）与糖原分解和糖异生相关的基因表达在从属裸鼹鼠/幼年裸鼹鼠的不同组织中有所不同，一些标志物下调、上调或不变，但在王后裸鼹鼠中总是不变或下调。综上所述，我们的结果表明，缺氧会上调从属裸鼹鼠和幼年裸鼹鼠的糖酵解和糖原动员，但不会上调王后裸鼹鼠的。
