{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T08:48:24Z","timestamp":1790671704031,"version":"4.1.0"},"reference-count":45,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T00:00:00Z","timestamp":1662249600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000844","name":"European Space Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000844","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100020624","name":"NIHR Nottingham Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100020624","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007743","name":"European Society for Clinical Nutrition and Metabolism","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007743","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","award":["BB\/P005004\/1"],"award-info":[{"award-number":["BB\/P005004\/1"]}],"id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Bed rest (BR) reduces whole\u2010body insulin\u2010stimulated glucose disposal (GD) and alters muscle fuel metabolism, but little is known about metabolic adaptation from acute to chronic BR nor the mechanisms involved, particularly when volunteers are maintained in energy balance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Healthy males (<jats:italic>n<\/jats:italic>\u00a0=\u00a010, 24.0\u00a0\u00b1\u00a01.3\u00a0years), maintained in energy balance, underwent 3\u2010day BR (acute BR). A second cohort matched for sex and body mass index (<jats:italic>n<\/jats:italic>\u00a0=\u00a020, 34.2\u00a0\u00b1\u00a01.8\u00a0years) underwent 56\u2010day BR (chronic BR). A hyperinsulinaemic euglycaemic clamp (60\u00a0mU\/m<jats:sup>2<\/jats:sup>\/min) was performed to determine rates of whole\u2010body insulin\u2010stimulated GD before and after BR (normalized to lean body mass). Indirect calorimetry was performed before and during steady state of each clamp to calculate rates of whole\u2010body fuel oxidation. Muscle biopsies were taken to determine muscle glycogen, metabolite and intramyocellular lipid (IMCL) contents, and the expression of 191 mRNA targets before and after BR. Two\u2010way repeated measures analysis of variance was used to detect differences in endpoint measures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Acute BR reduced insulin\u2010mediated GD (Pre 11.5\u00a0\u00b1\u00a00.7 vs. Post 9.3\u00a0\u00b1\u00a00.6\u00a0mg\/kg\/min, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), which was unchanged in magnitude following chronic BR (Pre 10.2\u00a0\u00b1\u00a00.4 vs. Post 7.9\u00a0\u00b1\u00a00.3\u00a0mg\/kg\/min, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). This reduction in GD was paralleled by the elimination of the 35% increase in insulin\u2010stimulated muscle glycogen storage following both acute and chronic BR. Acute BR had no impact on insulin\u2010stimulated carbohydrate (CHO; Pre 3.69\u00a0\u00b1\u00a00.39 vs. Post 4.34\u00a0\u00b1\u00a00.22\u00a0mg\/kg\/min) and lipid (Pre 1.13\u00a0\u00b1\u00a00.14 vs. Post 0.59\u00a0\u00b1\u00a00.11\u00a0mg\/kg\/min) oxidation, but chronic BR reduced CHO oxidation (Pre 3.34\u00a0\u00b1\u00a00.18 vs. Post 2.72\u00a0\u00b1\u00a00.13\u00a0mg\/kg\/min, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05) and blunted the magnitude of insulin\u2010mediated inhibition of lipid oxidation (Pre 0.60\u00a0\u00b1\u00a00.07 vs. Post 0.85\u00a0\u00b1\u00a00.06\u00a0mg\/kg\/min, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.05). Neither acute nor chronic BR increased muscle IMCL content. Plentiful mRNA abundance changes were detected following acute BR, which waned following chronic BR and reflected changes in fuel oxidation and muscle glycogen storage at this time point.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Acute BR suppressed insulin\u2010stimulated GD and storage, but the extent of this suppression increased no further in chronic BR. However, insulin\u2010mediated inhibition of fat oxidation after chronic BR was less than acute BR and was accompanied by blunted CHO oxidation. The juxtaposition of these responses shows that the regulation of GD and storage can be dissociated from substrate oxidation. Additionally, the shift in substrate oxidation after chronic BR was not explained by IMCL accumulation but reflected by muscle mRNA and pyruvate dehydrogenase kinase 4 protein abundance changes, pointing to lack of muscle contraction per se as the primary signal for muscle adaptation.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13075","type":"journal-article","created":{"date-parts":[[2022,9,4]],"date-time":"2022-09-04T21:30:30Z","timestamp":1662327030000},"page":"2999-3013","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Human adaptation to immobilization: Novel insights of impacts on glucose disposal and fuel utilization"],"prefix":"10.1002","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6622-2525","authenticated-orcid":false,"given":"Natalie F.","family":"Shur","sequence":"first","affiliation":[{"name":"Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, School of Life Sciences The University of Nottingham  Nottingham UK"},{"name":"National Institute for Health and Care Research (NIHR) Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Simpson","sequence":"additional","affiliation":[{"name":"National Institute for Health and Care Research (NIHR) Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and University of Nottingham  Nottingham UK"},{"name":"MRC\/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life Sciences and Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Crossland","sequence":"additional","affiliation":[{"name":"National Institute for Health and Care Research (NIHR) Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and University of Nottingham  Nottingham UK"},{"name":"MRC\/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life Sciences and Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Prince K.","family":"Chivaka","sequence":"additional","affiliation":[{"name":"Centre for Sport, Exercise and Osteoarthritis Research Versus Arthritis, School of Life Sciences The University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Despina","family":"Constantin","sequence":"additional","affiliation":[{"name":"National Institute for Health and Care Research (NIHR) Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and University of Nottingham  Nottingham UK"},{"name":"MRC\/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life Sciences and Medicine University of Nottingham  Nottingham 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Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and University of Nottingham  Nottingham UK"},{"name":"MRC\/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life Sciences and Medicine University of Nottingham  Nottingham UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nate","family":"Szewczyk","sequence":"additional","affiliation":[{"name":"National Institute for Health and Care Research (NIHR) Nottingham Biomedical Research Centre Nottingham University Hospitals NHS Trust and University of Nottingham  Nottingham UK"},{"name":"MRC\/Versus Arthritis Centre for Musculoskeletal Ageing Research, Schools of Life Sciences and Medicine University of Nottingham  Nottingham UK"},{"name":"Ohio Musculoskeletal and Neurological Institute, Heritage College of Osteopathic Medicine Ohio University  Athens OH 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