{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T04:13:28Z","timestamp":1785730408536,"version":"3.56.0"},"reference-count":62,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T00:00:00Z","timestamp":1641772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["04229"],"award-info":[{"award-number":["04229"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chairs","doi-asserted-by":"publisher","award":["950-230954"],"award-info":[{"award-number":["950-230954"]}],"id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["GM059785"],"award-info":[{"award-number":["GM059785"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Metabolites"],"abstract":"<jats:p>Hypoxia poses a major physiological challenge for mammals and has significant impacts on cellular and systemic metabolism. As with many other small rodents, naked mole-rats (NMRs; Heterocephalus glaber), who are among the most hypoxia-tolerant mammals, respond to hypoxia by supressing energy demand (i.e., through a reduction in metabolic rate mediated by a variety of cell- and tissue-level strategies), and altering metabolic fuel use to rely primarily on carbohydrates. However, little is known regarding specific metabolite changes that underlie these responses. We hypothesized that NMR tissues utilize multiple strategies in responding to acute hypoxia, including the modulation of signalling pathways to reduce anabolism and reprogram carbohydrate metabolism. To address this question, we evaluated changes of 64 metabolites in NMR brain and liver following in vivo hypoxia exposure (7% O2, 4 h). We also examined changes in matched tissues from similarly treated hypoxia-intolerant mice. We report that, following exposure to in vivo hypoxia: (1) phenylalanine, tyrosine and tryptophan anabolism are supressed both in NMR brain and liver; (2) carbohydrate metabolism is reprogramed in NMR brain and liver, but in a divergent manner; (3) redox state is significantly altered in NMR brain; and (4) the AMP\/ATP ratio is elevated in liver. Overall, our results suggest that hypoxia induces significant metabolic remodelling in NMR brain and liver via alterations of multiple metabolic pathways.<\/jats:p>","DOI":"10.3390\/metabo12010056","type":"journal-article","created":{"date-parts":[[2022,1,10]],"date-time":"2022-01-10T22:03:13Z","timestamp":1641852193000},"page":"56","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":28,"title":["Metabolomic Analysis of Carbohydrate and Amino Acid Changes Induced by Hypoxia in Naked Mole-Rat Brain and Liver"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5251-640X","authenticated-orcid":false,"given":"Hang","family":"Cheng","sequence":"first","affiliation":[{"name":"Biology Department, University of Ottawa, Ottawa, ON K1N 6N5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiming (Amy)","family":"Qin","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA"},{"name":"Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA"},{"name":"Interdisciplinary Graduate Program in Nutritional Sciences, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashpal","family":"Dhillon","sequence":"additional","affiliation":[{"name":"Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Dowell","sequence":"additional","affiliation":[{"name":"Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John M.","family":"Denu","sequence":"additional","affiliation":[{"name":"Department of Biomolecular Chemistry, University of Wisconsin-Madison, Madison, WI 53706, USA"},{"name":"Wisconsin Institute for Discovery, University of Wisconsin-Madison, Madison, WI 53706, USA"},{"name":"Morgridge Institute for Research, University of Wisconsin-Madison, Madison, WI 53706, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4035-9555","authenticated-orcid":false,"given":"Matthew E.","family":"Pamenter","sequence":"additional","affiliation":[{"name":"Biology Department, University of Ottawa, Ottawa, ON K1N 6N5, Canada"},{"name":"Brain and Mind Research Institute, University of Ottawa, Ottawa, ON K1H 8M5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,1,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"20170545","DOI":"10.1098\/rsbl.2017.0545","article-title":"Behavioural responses of naked mole rats to acute hypoxia and anoxia","volume":"13","author":"Ilacqua","year":"2017","journal-title":"Biol. 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