{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,31]],"date-time":"2026-03-31T04:04:45Z","timestamp":1774929885891,"version":"3.50.1"},"reference-count":59,"publisher":"The Company of Biologists","issue":"15","license":[{"start":{"date-parts":[[2021,8,1]],"date-time":"2021-08-01T00:00:00Z","timestamp":1627776000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.biologists.com\/user-licence-1-1\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chair","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001804","name":"Canada Research Chair","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001804","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Ontario Graduate Scholarship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,8,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n               <jats:p>Naked mole-rats reduce their metabolic requirements to tolerate severe hypoxia. However, the regulatory mechanisms that underpin this metabolic suppression have yet to be elucidated. 5\u2032-AMP-activated protein kinase (AMPK) is the cellular \u2018master\u2019 energy effector and we hypothesized that alterations in the AMPK pathway contribute to metabolic reorganization in hypoxic naked mole-rat skeletal muscle. To test this hypothesis, we exposed naked mole-rats to 4\u2005h of normoxia (21% O2) or severe hypoxia (3% O2), while indirectly measuring whole-animal metabolic rate and fuel preference. We then isolated skeletal muscle and assessed protein expression and post-translational modification of AMPK, and downstream changes in key glucose and fatty acid metabolic proteins mediated by AMPK, including acetyl-CoA carboxylase (ACC1), glycogen synthase (GS) and glucose transporters (GLUTs) 1 and 4. We found that in hypoxic naked mole-rats (1) metabolic rate decreased \u223c80% and fuel use switched to carbohydrates, and that (2) levels of activated phosphorylated AMPK and GS, and GLUT4 expression were downregulated in skeletal muscle, while ACC1 was unchanged. To explore the regulatory mechanism underlying this hypometabolic state, we used RT-qPCR to examine 55 AMPK-associated microRNAs (miRNAs), which are short non-coding RNA post-transcriptional silencers. We identified changes in 10 miRNAs (three upregulated and seven downregulated) implicated in AMPK downregulation. Our results suggest that miRNAs and post-translational mechanisms coordinately reduce AMPK activity and downregulate metabolism in naked mole-rat skeletal muscle during severe hypoxia. This novel mechanism may support tissue-specific prioritization of energy for more essential organs in hypoxia.<\/jats:p>","DOI":"10.1242\/jeb.242968","type":"journal-article","created":{"date-parts":[[2021,8,10]],"date-time":"2021-08-10T12:25:57Z","timestamp":1628598357000},"source":"Crossref","is-referenced-by-count":22,"title":["MicroRNA-mediated inhibition of AMPK coordinates tissue-specific downregulation of skeletal muscle metabolism in hypoxic naked mole-rats"],"prefix":"10.1242","volume":"224","author":[{"given":"Hanane","family":"Hadj-Moussa","sequence":"first","affiliation":[{"name":"Department of Biology and Institute of Biochemistry, Carleton University, Ottawa, ON, Canada, K1S 5B6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah","family":"Chiasson","sequence":"additional","affiliation":[{"name":"Biology Department, University of Ottawa, Ottawa, ON, Canada, K1N 9A7"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hang","family":"Cheng","sequence":"additional","affiliation":[{"name":"Biology Department, University of Ottawa, Ottawa, ON, Canada, K1N 9A7"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liam","family":"Eaton","sequence":"additional","affiliation":[{"name":"Biology Department, University of Ottawa, Ottawa, ON, Canada, K1N 9A7"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenneth B.","family":"Storey","sequence":"additional","affiliation":[{"name":"Department of Biology and Institute of Biochemistry, Carleton University, Ottawa, ON, Canada, K1S 5B6"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"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, Canada, K1N 9A7"},{"name":"Brain and Mind Research Institute, University of Ottawa, Ottawa, ON, Canada, K1H 8M5"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"237","published-online":{"date-parts":[[2021,8,10]]},"reference":[{"key":"2021081012252975400_JEB242968C1","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1006\/abbi.2000.1935","article-title":"Stimulation of AMP-activated protein kinase (AMPK) is associated with enhancement of Glut1-mediated glucose transport","volume":"380","author":"Abbud","year":"2000","journal-title":"Arch. 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