{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T17:16:51Z","timestamp":1789751811363,"version":"4.0.1"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T00:00:00Z","timestamp":1773878400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R01 AG077812"],"award-info":[{"award-number":["R01 AG077812"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["P30AG050911"],"award-info":[{"award-number":["P30AG050911"]}],"id":[{"id":"10.13039\/100000049","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":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Cancer cachexia is a muscle wasting syndrome that occurs in ~80% of cancer patients and is the primary cause of death for 22%\u201330% of cancer patients. The primary challenge associated with cancer cachexia is that effective therapies to treat the associated muscle loss and dysfunction are lacking. Research exploring whether reactive oxygen species (ROS, i.e., superoxide anion and hydrogen peroxide) contributes to cancer cachexia has had mixed results. Lipid peroxidation is an underexplored component of oxidative stress that may contribute to cancer cachexia as markers of lipid peroxidation such as 4\u2010hydroxyneoneal (4\u2010HNE) and MDA (Malondialdehyde) are higher in muscle from tumour\u2010bearing mice when compared to controls. Phospholipid hydroperoxide glutathione peroxidase (GPx4) is an antioxidant enzyme that reduces lipid hydroperoxides. We hypothesized that reducing lipid peroxidation via GPx4 overexpression would mitigate cancer cachexia in tumour\u2010bearing mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>One million Lewis lung carcinoma (LLC) cells or phosphate\u2010buffered saline was injected into the hind flank of wildtype or GPx4 transgenic (Tg) mice at 6\u2009months of age and the tumour developed for 4\u2009weeks. Muscle mass, contractile function, mitochondrial respiration, RNA\u2010sequencing, inflammation and the oxylipin profile were assessed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Muscle mass and myofiber cross\u2010sectional area were reduced ~25% in wildtype tumour\u2010bearing mice compared to control mice but not changed in GPx4 Tg tumour\u2010bearing mice. GPx4 overexpression (~3\u2010fold) did not raise maximal or specific muscle force generation in LLC\u2010tumour\u2010bearing mice. Muscle mitochondrial respiration was reduced in wildtype tumour\u2010bearing mice by ~40% when compared to control mice but not altered in tumour\u2010bearing GPx4 Tg mice. Quadricep RNA seq analysis revealed that expression of inflammatory genes was elevated in wildtype tumour\u2010bearing mice when compared to control mice, and the expression of these genes was reduced in tumour\u2010bearing GPx4 Tg mice compared to wildtype tumour\u2010bearing mice. Next, we found that protein content of IL\u20106 was ~5\u2010fold greater in muscle from wildtype tumour\u2010bearing mice compared to control mice, and GPx4 overexpression prevented this increase in IL\u20106. We assessed the muscle oxylipin profile and found that many oxylipins generated by 12\/15\u2010Lox were elevated in tumour\u2010bearing mice but not impacted by GPx4 overexpression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our results show that GPx4 overexpression protected muscle mass and mitochondrial respiration in tumour\u2010bearing mice, possibly by reducing muscle inflammation. Future studies will explore the potential mechanisms for the protective effect of GPx4 in cancer cachexia.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/jcsm.70255","type":"journal-article","created":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T12:39:54Z","timestamp":1773923994000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Phospholipid Glutathione Peroxidase Overexpression Mitigates Cancer Cachexia by Protecting Muscle Mass and Lowering Inflammation"],"prefix":"10.1002","volume":"17","author":[{"given":"Elizabeth","family":"Duggan","sequence":"first","affiliation":[{"name":"Aging and Metabolism Research Program Oklahoma Medical Research Foundation  Oklahoma City Oklahoma USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan\u00a0D.","family":"Fuqua","sequence":"additional","affiliation":[{"name":"Aging and Metabolism Research Program Oklahoma Medical Research 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