{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T22:44:30Z","timestamp":1791931470995,"version":"4.3.4"},"reference-count":45,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2022,2,3]],"date-time":"2022-02-03T00:00:00Z","timestamp":1643846400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J cachexia sarcopenia muscle"],"published-print":{"date-parts":[[2022,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Iron excess has been proposed as an essential factor in skeletal muscle wasting. Studies have reported correlations between muscle iron accumulation and atrophy, either through ageing or by using experimental models of secondary iron overload. However, iron treatments performed in most of these studies induced an extra\u2010pathophysiological iron overload, more representative of intoxication or poisoning. The main objective of this study was to determine the impact of iron excess closer to pathophysiological conditions on structural and metabolic adaptations (i) in differentiated myotubes and (ii) in skeletal muscle exhibiting oxidative (i.e. the soleus) or glycolytic (i.e. the gastrocnemius) metabolic phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The impact of iron excess was assessed in both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> models. Murine differentiated myotubes were exposed to ferric ammonium citrate (FAC) (i.e. 10 and 50\u00a0\u03bcM) for the <jats:italic>in vitro<\/jats:italic> component. The <jats:italic>in vivo<\/jats:italic> model was achieved by a single iron dextran subcutaneous injection (1\u00a0g\/kg) in mice. Four months after the injection, soleus and gastrocnemius muscles were harvested for analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>In vitro<\/jats:italic>, iron exposure caused dose\u2010dependent increases of iron storage protein ferritin (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.01) and dose\u2010dependent decreases of mRNA TfR1 levels (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001), which support cellular adaptations to iron excess. Extra\u2010physiological iron treatment (50\u00a0\u03bcM FAC) promoted myotube atrophy (<jats:italic>P<\/jats:italic>\u00a0=\u00a00.018), whereas myotube size remained unchanged under pathophysiological treatment (10\u00a0\u03bcM FAC). FAC treatments, whatever the doses tested, did not affect the expression of proteolytic markers (i.e. NF\u2010\u03baB, MurF1, and ubiquitinated proteins). <jats:italic>In vivo<\/jats:italic>, basal iron content and mRNA TfR1 levels were significantly higher in the soleus compared with the gastrocnemius (+130% and +127%; <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001, respectively), supporting higher iron needs in oxidative skeletal muscle. Iron supplementation induced muscle iron accumulation in the soleus and gastrocnemius muscles (+79%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001 and +34%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002, respectively), but ferritin protein expression only increased in the gastrocnemius (+36%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.06). Despite iron accumulation, muscle weight, fibre diameter, and myosin heavy chain distribution remained unchanged in either skeletal muscle.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Together, these data support that under pathophysiological conditions, skeletal muscle can protect itself from the related deleterious effects of excess iron.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.12897","type":"journal-article","created":{"date-parts":[[2022,2,4]],"date-time":"2022-02-04T07:38:22Z","timestamp":1643960302000},"page":"1250-1261","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Oxidative and glycolytic skeletal muscles deploy protective mechanisms to avoid atrophy under pathophysiological iron overload"],"prefix":"10.1002","volume":"13","author":[{"given":"David","family":"Martin","sequence":"first","affiliation":[{"name":"Laboratory \u2018Movement, Sport and Health Sciences\u2019\u2014EA7470 University of Rennes\/ENS Rennes  Bruz France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K\u00e9vin","family":"Nay","sequence":"additional","affiliation":[{"name":"Laboratory \u2018Movement, Sport and Health Sciences\u2019\u2014EA7470 University of Rennes\/ENS Rennes  Bruz France"},{"name":"Exercise and Nutrition Research Program, Mary MacKillop Institute for Health Research Australian Catholic University  Melbourne Vic. Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fran\u00e7ois","family":"Robin","sequence":"additional","affiliation":[{"name":"INSERM, INRAe, University of Rennes, Nutrition Metabolisms and Cancer Institute (NuMeCan), Platform AEM2, CHU Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Am\u00e9lie","family":"Rebillard","sequence":"additional","affiliation":[{"name":"Laboratory \u2018Movement, Sport and Health Sciences\u2019\u2014EA7470 University of Rennes\/ENS Rennes  Bruz France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luz","family":"Orfila","sequence":"additional","affiliation":[{"name":"Laboratory \u2018Movement, Sport and Health Sciences\u2019\u2014EA7470 University of Rennes\/ENS Rennes  Bruz France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brice","family":"Martin","sequence":"additional","affiliation":[{"name":"Laboratory \u2018Movement, Sport and Health Sciences\u2019\u2014EA7470 University of Rennes\/ENS Rennes  Bruz France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia","family":"Leroyer","sequence":"additional","affiliation":[{"name":"INSERM, INRAe, University of Rennes, Nutrition Metabolisms and Cancer Institute (NuMeCan), Platform AEM2, CHU Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pascal","family":"Guggenbuhl","sequence":"additional","affiliation":[{"name":"INSERM, INRAe, University of Rennes, Nutrition Metabolisms and Cancer Institute (NuMeCan), Platform AEM2, CHU Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne","family":"Dufresne","sequence":"additional","affiliation":[{"name":"Laboratory \u2018Movement, Sport and Health Sciences\u2019\u2014EA7470 University of Rennes\/ENS Rennes  Bruz France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Noirez","sequence":"additional","affiliation":[{"name":"IRMES\u2014Institute for Research in Medicine and Epidemiology of Sport, INSEP  Paris France"},{"name":"INSERM S1124, Universit\u00e9 de Paris  Paris France"},{"name":"EA7507, Performance Health Metrology Society, Universit\u00e9 de Reims Champagne Ardenne  Reims France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Ropert","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Biochimie CHU Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lor\u00e9al","sequence":"additional","affiliation":[{"name":"INSERM, INRAe, University of Rennes, Nutrition Metabolisms and Cancer Institute (NuMeCan), Platform AEM2, CHU Rennes  Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1531-6425","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Derbr\u00e9","sequence":"additional","affiliation":[{"name":"Laboratory \u2018Movement, Sport and Health Sciences\u2019\u2014EA7470 University of Rennes\/ENS Rennes  Bruz France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2022,2,3]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1249\/MSS.0000000000000975"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1532-5415.2003.51152.x"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13054-015-0993-7"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.12.028"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.010389"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201902102RR"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00165"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jamda.2017.05.026"},{"key":"e_1_2_8_10_1","article-title":"Relationship between serum ferritin levels and sarcopenia in Korean females aged 60\u00a0years and older using the fourth Korea National Health and Nutrition Examination Survey (KNHANES IV\u20102, 3), 2008\u20132009","volume":"9","author":"Kim TH","year":"2014","journal-title":"PLoS ONE"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1309\/LMF28S2GIMXNWHMM"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio807"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(02)01006-7"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3892\/mmr.2013.1316"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/path.4822"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0148292"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112915"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbagen.2011.07.014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1136\/jcp.2010.079046"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2013.08.011"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exger.2008.02.007"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2007.039453"},{"key":"e_1_2_8_23_1","first-page":"2678","article-title":"Iron limitation promotes the atrophy of skeletal myocytes, whereas iron supplementation prevents this process in the hypoxic conditions","volume":"41","author":"Kobak K","year":"2018","journal-title":"Int J Mol Med"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtemb.2016.01.011"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1113\/expphysiol.2008.046045"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2015.11.009"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201801381RR"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M008923200"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00720.2015"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1113\/EP088339"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00521.2018"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2014.09.009"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijbs.53126"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201802724RR"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00368.2011"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101643"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejcb.2015.05.003"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1992.tb06441.x"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2020.8167"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1177\/000456329803500601"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2019.08.001"},{"key":"e_1_2_8_42_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2017.00788"},{"key":"e_1_2_8_43_1","first-page":"853","article-title":"Recognition and management of hereditary hemochromatosis","volume":"65","author":"Brandhagen DJ","year":"2002","journal-title":"Am Fam Physician"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.21585"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00237.2018"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018617"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12897","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jcsm.12897","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.12897","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,25]],"date-time":"2023-08-25T16:32:45Z","timestamp":1692981165000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.12897"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,2,3]]},"references-count":45,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2022,4]]}},"alternative-id":["10.1002\/jcsm.12897"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.12897","archive":["Portico"],"relation":{},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,2,3]]},"assertion":[{"value":"2021-06-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-11-22","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2022-02-03","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}