{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:17:07Z","timestamp":1790173027476,"version":"4.1.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2021,8,30]],"date-time":"2021-08-30T00:00:00Z","timestamp":1630281600000},"content-version":"vor","delay-in-days":2634,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/3.0\/"}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2014,7,1]]},"abstract":"<jats:p>Obesity-induced white adipose tissue (WAT) inflammation and insulin resistance are associated with macrophage (M\u0444) infiltration and phenotypic shift from \u201canti-inflammatory\u201d M2-like to predominantly \u201cproinflammatory\u201d M1-like cells. Erythropoietin (EPO), a glycoprotein hormone indispensable for erythropoiesis, has biological activities that extend to nonerythroid tissues, including antiapoptotic and anti-inflammatory effects. Using comprehensive in vivo and in vitro analyses in mice, EPO treatment inhibited WAT inflammation, normalized insulin sensitivity, and reduced glucose intolerance. We investigated EPO receptor (EPO-R) expression in WAT and characterized the role of its signaling during obesity-induced inflammation. Remarkably, and prior to any detectable changes in body weight or composition, EPO treatment reduced M1-like M\u0444 and increased M2-like M\u0444 in WAT, while decreasing inflammatory monocytes. These anti-inflammatory effects were found to be driven, at least in part, by direct EPO-R response in M\u0444 via Stat3 activation, where EPO effects on M2 but not M1 M\u0444 required interleukin-4 receptor\/Stat6. Using obese \u2206EpoR mice with EPO-R restricted to erythroid cells, we demonstrated an anti-inflammatory role for endogenous EPO. Collectively, our findings identify EPO-R signaling as a novel regulator of WAT inflammation, extending its nonerythroid activity to encompass effects on both M\u0444 infiltration and subset composition in WAT.<\/jats:p>","DOI":"10.2337\/db13-0883","type":"journal-article","created":{"date-parts":[[2014,3,20]],"date-time":"2014-03-20T04:00:30Z","timestamp":1395288030000},"page":"2415-2431","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":48,"title":["Erythropoietin Signaling: A Novel Regulator of White Adipose Tissue Inflammation During Diet-Induced Obesity"],"prefix":"10.2337","volume":"63","author":[{"given":"Mawadda","family":"Alnaeeli","sequence":"first","affiliation":[{"name":"Molecular Medicine Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce 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