{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:37:25Z","timestamp":1791254245910,"version":"4.1.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T00:00:00Z","timestamp":1703030400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["AG076075"],"award-info":[{"award-number":["AG076075"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["AG074535"],"award-info":[{"award-number":["AG074535"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["GM144613"],"award-info":[{"award-number":["GM144613"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["DK127979"],"award-info":[{"award-number":["DK127979"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000272","name":"National Institute for Health and Care Research","doi-asserted-by":"publisher","award":["DK107397"],"award-info":[{"award-number":["DK107397"]}],"id":[{"id":"10.13039\/501100000272","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008732","name":"Uehara Memorial Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008732","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":[[2024,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Lipid hydroperoxides (LOOH) have been implicated in skeletal muscle atrophy with age and disuse. Lysophosphatidylcholine acyltransferase 3 (LPCAT3), an enzyme of the Lands cycle, conjugates a polyunsaturated fatty acyl chain to a lysophospholipid to form a polyunsaturated fatty acid containing phospholipid (PUFA\u2010PL) molecule, providing substrates for LOOH propagation. Previous studies suggest that inhibition of the Lands cycle is an effective strategy to suppress LOOH. Mice with skeletal muscle\u2010specific tamoxifen\u2010inducible knockout of LPCAT3 (LPCAT3\u2010MKO) were utilized to determine if muscle\u2010specific attenuation of LOOH may alleviate muscle atrophy and weakness with disuse.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LPCAT3\u2010MKO and control mice underwent 7\u00a0days of sham or hindlimb unloading (HU model) to study muscle mass and force\u2010generating capacity. LOOH was assessed by quantifying 4\u2010hydroxynonenal (4\u2010HNE)\u2010conjugated peptides. Quantitative PCR and lipid mass spectrometry were used to validate LPCAT3 deletion.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Seven days of HU was sufficient to induce muscle atrophy and weakness concomitant to a ~2\u2010fold increase in 4\u2010HNE (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0069). Deletion of LPCAT3 reversed HU\u2010induced increase in muscle 4\u2010HNE (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0256). No difference was found in body mass, body composition, or caloric intake between genotypes. The soleus (SOL) and plantaris (PLANT) muscles of the LPCAT3\u2010MKO mice experienced ~15% and ~40% less atrophy than controls, respectively. (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0011 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0265). Type I and IIa SOL myofibers experienced a ~40% decrease in cross sectional area (CSA), which was attenuated to only 15% in the LPCAT3\u2010MKO mice (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0170 and\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a00.0411, respectively). Strikingly, SOL muscles were fully protected and extensor digitorum longus (EDL) muscles experienced a ~35% protection from HU\u2010induced reduction in force\u2010generating capacity in the LPCAT3\u2010MKO mice compared with controls (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0&lt;\u00a00.0001 for both muscles).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our findings demonstrate that attenuation of skeletal muscle lipid hydroperoxides is sufficient to restore its function, in particular a protection from reduction in muscle specific force. Our findings suggest muscle lipid peroxidation contributes to atrophy and weakness induced by disuse in mice.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.13406","type":"journal-article","created":{"date-parts":[[2023,12,20]],"date-time":"2023-12-20T20:18:45Z","timestamp":1703103525000},"page":"319-330","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Inhibition of the skeletal muscle Lands cycle ameliorates weakness induced by physical inactivity"],"prefix":"10.1002","volume":"15","author":[{"given":"Justin L.","family":"Shahtout","sequence":"first","affiliation":[{"name":"Diabetes and Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Department of Physical Therapy and Athletic Training University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroaki","family":"Eshima","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Molecular Medicine Program University of Utah  Salt Lake City Utah USA"},{"name":"Nagasaki International University  Sasebo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick J.","family":"Ferrara","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Molecular Medicine Program University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Alan","family":"Maschek","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Metabolomics, Mass Spectrometry, and Proteomics Core University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E.","family":"Cox","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Metabolomics, Mass Spectrometry, and Proteomics Core University of Utah  Salt Lake City Utah USA"},{"name":"Department of Biochemistry University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micah J.","family":"Drummond","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Department of Physical Therapy and Athletic Training University of Utah  Salt Lake City Utah USA"},{"name":"Molecular Medicine Program University of Utah  Salt Lake City Utah USA"},{"name":"Department of Nutrition and Integrative Physiology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3802-4756","authenticated-orcid":false,"given":"Katsuhiko","family":"Funai","sequence":"additional","affiliation":[{"name":"Diabetes and Metabolism Research Center University of Utah  Salt Lake City Utah USA"},{"name":"Department of Physical Therapy and Athletic Training University of Utah  Salt Lake City Utah USA"},{"name":"Molecular Medicine Program University of Utah  Salt Lake City Utah USA"},{"name":"Department of Biochemistry University of Utah  Salt Lake City Utah USA"},{"name":"Department of Nutrition and Integrative Physiology University of Utah  Salt Lake City Utah USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,20]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2013.06.011"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2013.07.003"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2011.3973"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102518"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.85289"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-70792-7"},{"key":"e_1_2_7_8_1","first-page":"338","article-title":"Chicken or egg? Mitochondrial phospholipids and oxidative stress in disuse\u2010induced skeletal muscle atrophy","volume":"38","author":"Miranda ER","year":"2022","journal-title":"Antioxid Redox Signal"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.03.042"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)70453-5"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1089\/ars.2017.7124"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchembio.2238"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2013.12.010"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M115.680090"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nbd.2016.05.011"},{"key":"e_1_2_7_16_1","first-page":"2099","article-title":"Nonenal (4\u2010HNE) induces insulin resistance in skeletal muscle through both carbonyl and oxidative","volume":"153","author":"Pillon NJ","year":"2012","journal-title":"Stress"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-017-4528-4"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI94307"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmet.2015.04.001"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/nutd.2013.30"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1582-4934.2010.01101.x"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcsm.12794"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101006"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201900095R"},{"key":"e_1_2_7_25_1","first-page":"1459","article-title":"Mitochondrial\u2010targeted antioxidants protect skeletal muscle against immobilization\u2010induced muscle atrophy","author":"Min K","year":"2022","journal-title":"J Appl Physiol"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00494.2020"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00767.2006"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11357-020-00189-x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aax8352"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.yjmcc.2018.07.001"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M806311200"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2023.102761"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI135963"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1152\/japplphysiol.00456.2019"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.202101104R"},{"key":"e_1_2_7_36_1","first-page":"1","article-title":"Lpcat3\u2010dependent production of arachidonoyl phospholipids is a key determinant of triglyceride secretion","author":"Rong X","year":"2015","journal-title":"Elife"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41581-023-00689-x"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2016.10.497"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2013.10.002"},{"key":"e_1_2_7_40_1","article-title":"Muscle weakness precedes atrophy during cancer cachexia and is linked to muscle\u2010specific mitochondrial stress. JCI","volume":"7","author":"Delfinis LJ","year":"2022","journal-title":"Insight"}],"container-title":["Journal of Cachexia, Sarcopenia and Muscle"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jcsm.13406","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,1]],"date-time":"2024-02-01T21:29:36Z","timestamp":1706822976000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jcsm.13406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,20]]},"references-count":39,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,2]]}},"alternative-id":["10.1002\/jcsm.13406"],"URL":"https:\/\/doi.org\/10.1002\/jcsm.13406","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.07.25.550576","asserted-by":"object"}]},"ISSN":["2190-5991","2190-6009"],"issn-type":[{"value":"2190-5991","type":"print"},{"value":"2190-6009","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,20]]},"assertion":[{"value":"2023-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}