First Author | Alnaeeli M | Year | 2014 |
Journal | Diabetes | Volume | 63 |
Issue | 7 | Pages | 2415-31 |
PubMed ID | 24647735 | Mgi Jnum | J:229804 |
Mgi Id | MGI:5754478 | Doi | 10.2337/db13-0883 |
Citation | Alnaeeli M, et al. (2014) Erythropoietin signaling: a novel regulator of white adipose tissue inflammation during diet-induced obesity. Diabetes 63(7):2415-31 |
abstractText | Obesity-induced white adipose tissue (WAT) inflammation and insulin resistance are associated with macrophage (Msmall ef, Cyrillic) infiltration and phenotypic shift from "anti-inflammatory" M2-like to predominantly "proinflammatory" 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 Msmall ef, Cyrillic and increased M2-like Msmall ef, Cyrillic 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 Msmall ef, Cyrillic via Stat3 activation, where EPO effects on M2 but not M1 Msmall ef, Cyrillic required interleukin-4 receptor/Stat6. Using obese EpoR 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 Msmall ef, Cyrillic infiltration and subset composition in WAT. |