{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T17:22:42Z","timestamp":1790788962245,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T00:00:00Z","timestamp":1713312000000},"content-version":"vor","delay-in-days":16,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council of Canada","doi-asserted-by":"publisher","award":["RGPIN\u20102021\u201003603"],"award-info":[{"award-number":["RGPIN\u20102021\u201003603"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Chemotherapy is a major contributor to cachexia, but studies often investigate male animals. Here, we investigated whether sex modifies the effects of chemotherapy on cachexia and BCAA metabolism. Ten\u2010week\u2010old CD2F1 male and female mice were treated with the chemotherapy drug cocktail folfiri (50\u2009mg\/kg 5\u2010fluorouracil, 90\u2009mg\/kg leucovorin, and 24\u2009mg\/kg CPT11) (drug) or vehicle twice a week for 6\u2009weeks. Insulin tolerance tests were conducted and BCAA levels and metabolism were measured in plasma and tissues. Drug treatment reduced body and skeletal muscle weights and anabolic signaling in both sexes, with females showing worsened outcomes (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05 for all). Drug treatment increased plasma BCAA only in males, but BCAA concentrations in the skeletal muscle of both sexes were decreased; this decrease was more profound in males (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0097). In addition, muscle expression of the BCAA transporter LAT1 was reduced; this reduction was more severe in females (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.0264). In both sexes, the (inhibitory) phosphorylation of BCKD\u2010E1\u03b1\n                    <jats:sup>ser293<\/jats:sup>\n                    was increased along with decreased BCKD activity. In the liver, drug treatment increased BCAA concentrations and LAT1 expression, but BCKD activity was suppressed in both sexes (\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.05 for all). Our results demonstrate that altered BCAA metabolism may contribute to chemotherapy\u2010induced cachexia in a sex\u2010dependent manner.\n                  <\/jats:p>","DOI":"10.14814\/phy2.16003","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T21:15:12Z","timestamp":1713388512000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Sex differences in cachexia and branched\u2010chain amino acid metabolism following chemotherapy in mice"],"prefix":"10.14814","volume":"12","author":[{"given":"Stephen","family":"Mora","sequence":"first","affiliation":[{"name":"Muscle Health Research Centre, School of Kinesiology and Health Science York University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gagandeep","family":"Mann","sequence":"additional","affiliation":[{"name":"Muscle Health Research Centre, School of Kinesiology and Health Science York University  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9697-9318","authenticated-orcid":false,"given":"Olasunkanmi A. 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