{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:16:53Z","timestamp":1790662613989,"version":"4.1.0"},"reference-count":46,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T00:00:00Z","timestamp":1688083200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002997","name":"Nierstichting","doi-asserted-by":"publisher","award":["17OKG18"],"award-info":[{"award-number":["17OKG18"]}],"id":[{"id":"10.13039\/501100002997","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":[[2023,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Loss of muscle mass is linked with impaired quality of life and an increased risk of morbidity and premature mortality. Iron is essential for cellular processes such as energy metabolism, nucleotide synthesis and numerous enzymatic reactions. As the effects of iron deficiency (ID) on muscle mass and function are largely unknown, we aimed to assess the relation between ID and muscle mass in a large population\u2010based cohort, and subsequently studied effects of ID on cultured skeletal myoblasts and differentiated myocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In a population\u2010based cohort of 8592 adults, iron status was assessed by plasma ferritin and transferrin saturation, and muscle mass was estimated using 24\u2010h urinary creatinine excretion rate (CER). The relationships of ferritin and transferrin saturation with CER were assessed by multivariable logistic regression. Furthermore, mouse C2C12 skeletal myoblasts and differentiated myocytes were subjected to deferoxamine with or without ferric citrate. Myoblast proliferation was measured with a colorimetric 5\u2010bromo\u20102\u2032\u2010deoxy\u2010uridine ELISA assay. Myocyte differentiation was assessed using Myh7\u2010stainings. Myocyte energy metabolism, oxygen consumption rate and extracellular acidification rate were assessed using Seahorse mitochondrial flux analysis, and apoptosis rate with fluorescence\u2010activated cell sorting. RNA sequencing (RNAseq) was used to identify ID\u2010related gene and pathway enrichment in myoblasts and myocytes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Participants in the lowest age\u2010 and sex\u2010specific quintile of plasma ferritin (OR vs middle quintile 1.62, 95% CI 1.25\u20132.10, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) or transferrin saturation (OR 1.34, 95% CI 1.03\u20131.75, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.03) had a significantly higher risk of being in the lowest age\u2010 and sex\u2010specific quintile of CER, independent of body mass index, estimated GFR, haemoglobin, hs\u2010CRP, urinary urea excretion, alcohol consumption and smoking status. In C2C12 myoblasts, deferoxamine\u2010induced ID reduced myoblast proliferation rate (<jats:italic>P<\/jats:italic>\u2010trend &lt;0.001) but did not affect differentiation. In myocytes, deferoxamine reduced myoglobin protein expression (\u221252%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00.001) and tended to reduce mitochondrial oxygen consumption capacity (\u221228%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.10). Deferoxamine induced gene expression of cellular atrophy markers <jats:italic>Trim63<\/jats:italic> (+20%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.002) and <jats:italic>Fbxo32<\/jats:italic> (+27%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.048), which was reversed by ferric citrate (\u221231%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.04 and \u221226%, <jats:italic>P<\/jats:italic>\u00a0=\u00a00.004, respectively). RNAseq indicated that both in myoblasts and myocytes, ID predominantly affected genes involved in glycolytic energy metabolism, cell cycle regulation and apoptosis; co\u2010treatment with ferric citrate reversed these effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>In population\u2010dwelling individuals, ID is related to lower muscle mass, independent of haemoglobin levels and potential confounders. ID impaired myoblast proliferation and aerobic glycolytic capacity, and induced markers of myocyte atrophy and apoptosis. These findings suggest that ID contributes to loss of muscle mass.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jcsm.13277","type":"journal-article","created":{"date-parts":[[2023,6,30]],"date-time":"2023-06-30T07:39:20Z","timestamp":1688110760000},"page":"1865-1879","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["Iron deficiency is related to lower muscle mass in community\u2010dwelling individuals and impairs myoblast proliferation"],"prefix":"10.1002","volume":"14","author":[{"given":"Joanna Sophia J.","family":"Vinke","sequence":"first","affiliation":[{"name":"Departments of Nephrology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan R.","family":"Gorter","sequence":"additional","affiliation":[{"name":"Departments of Nephrology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele F.","family":"Eisenga","sequence":"additional","affiliation":[{"name":"Departments of Nephrology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wendy A.","family":"Dam","sequence":"additional","affiliation":[{"name":"Departments of Nephrology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"van der Meer","sequence":"additional","affiliation":[{"name":"Department of Cardiology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"van den Born","sequence":"additional","affiliation":[{"name":"Departments of Nephrology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan J.L.","family":"Bakker","sequence":"additional","affiliation":[{"name":"Departments of Nephrology University Medical Center Groningen, University of Groningen  Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martijn F.","family":"Hoes","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Maastricht University Medical Center+  Maastricht The Netherlands"},{"name":"CARIM School for Cardiovascular Diseases  Maastricht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4127-8733","authenticated-orcid":false,"given":"Martin H.","family":"de Borst","sequence":"additional","affiliation":[{"name":"Departments of Nephrology University Medical Center Groningen, University of Groningen  Groningen The 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