{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T01:51:31Z","timestamp":1790387491065,"version":"4.1.0"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T00:00:00Z","timestamp":1566345600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Some chemotherapeutic agents have been shown to lead to the severe wasting syndrome known as cachexia resulting in dramatic losses of both skeletal muscle and adipose tissue. Previous studies have shown that chemotherapy-induced cachexia is characterized by unique metabolic alterations. Recent results from our laboratory and others have shown that the use of ACVR2B\/Fc, a soluble form of the activin receptor 2B (ACVR2B), can mitigate muscle wasting induced by chemotherapy, although the underlying mechanisms responsible for such protective effects are unclear. In order to understand the biochemical mechanisms through which ACVR2B\/Fc functions, we employed a comprehensive, multi-platform metabolomics approach. Using both nuclear magnetic resonance (NMR) and mass-spectrometry (MS), we profiled the metabolome of both serum and muscle tissue from four groups of mice including (1) vehicle, (2) the chemotherapeutic agent, Folfiri, (3) ACVR2B\/Fc alone, and (4) combined treatment with both Folfiri and ACVR2B\/Fc. The metabolic profiles demonstrated large effects with Folfiri treatment and much weaker effects with ACVR2B\/Fc treatment. Interestingly, a number of significant effects were observed in the co-treatment group, with the addition of ACVR2B\/Fc providing some level of rescue to the perturbations induced by Folfiri alone. The most prominent of these were a normalization of systemic glucose and lipid metabolism. Identification of these pathways provides important insights into the mechanism by which ACVR2B\/Fc protects against chemotherapy-induced cachexia.<\/jats:p>","DOI":"10.3390\/cancers11091222","type":"journal-article","created":{"date-parts":[[2019,8,21]],"date-time":"2019-08-21T11:19:06Z","timestamp":1566386346000},"page":"1222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Treatment with Soluble Activin Receptor Type IIB Alters Metabolic Response in Chemotherapy-Induced Cachexia"],"prefix":"10.3390","volume":"11","author":[{"given":"Thomas M.","family":"O\u2019Connell","sequence":"first","affiliation":[{"name":"Department of Otolaryngology-Head &amp; Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Pin","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion E.","family":"Couch","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology-Head &amp; Neck Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3235-1871","authenticated-orcid":false,"given":"Andrea","family":"Bonetto","sequence":"additional","affiliation":[{"name":"Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"472","DOI":"10.3389\/fphys.2016.00472","article-title":"Cancer and Chemotherapy Contribute to Muscle Loss by Activating Common Signaling Pathways","volume":"7","author":"Barreto","year":"2016","journal-title":"Front Physiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"43442","DOI":"10.18632\/oncotarget.9779","article-title":"Chemotherapy-Related cachexia is associated with mitochondrial depletion and the activation of ERK1\/2 and p38 MAPKs","volume":"7","author":"Barreto","year":"2016","journal-title":"Oncotarget"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2543","DOI":"10.1089\/ars.2011.3965","article-title":"Chemotherapy-Induced weakness and fatigue in skeletal muscle: The role of oxidative stress","volume":"15","author":"Gilliam","year":"2011","journal-title":"Antioxid. 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